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Drugs for Type 2 Diabetes – Project Protocol

August 2016

Introduction and Rationale

The purpose of this project is to assess the clinical and cost-effectiveness of new drugs for the treatment of patients with type 2 diabetes. In August 2010, CADTH published an Optimal Therapy Report that assessed the clinical and cost-effectiveness of second-line therapies for patients with type 2 diabetes inadequately controlled on metformin.1The results from the CADTH review indicated that there were no apparent differences in efficacy across drug classes, and that sulfonylureas were the most cost-effective treatment option. Based on these analyses, the Canadian Optimal Medication Prescribing and Utilization Service (COMPUS) Expert Review Committee (CERC) recommended that most patients requiring a second treatment after metformin should be prescribed a sulfonylurea. CADTH followed this report with a therapeutic review that examined the evidence for third-line treatment options for adults with type 2 diabetes inadequately controlled on metformin and a sulfonylurea.2 The results demonstrated that insulins (basal, biphasic, bolus), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, and thiazolidinediones (TZDs) all produced statistically significant reductions in glycated hemoglobin A1C in combination with metformin and a sulfonylurea. Meglitinides and alpha-glucosidase inhibitors, however, did not. The addition of insulin neutral protamine Hagedorn (NPH) to metformin plus a sulfonylurea was associated with the most favourable cost-effectiveness estimates. CADTH’s Therapeutic Review Panel recommended that, for most adults with type 2 diabetes inadequately controlled on metformin and a sulfonylurea, insulin NPH should be added as the third-line agent. Long-acting insulin analogues at prices similar to insulin NPH were also considered an option for patients inadequately controlled on metformin and a sulfonylurea. 

Both original clinical reviews were updated in July 2013 to include new drugs approved for use in Canada and to expand the original economic analyses and recommendations based on these updates.3,4There was additional interest in the combined use of incretins and insulin, as some incretins received regulatory approval for combined use with insulin in Canada and other jurisdictions. Hence, the updated clinical review also addressed a supplemental research topic regarding the combination use of incretin agents with insulin.

Since then, a new drug class has entered the Canadian market for the treatment of patients with type 2 diabetes — sodium-glucose cotransporter-2 (SGLT-2) inhibitors. In addition, a fourth DPP-4 inhibitor (alogliptin) as well as a third GLP-1 analogue (dulaglutide) have appeared on the Canadian market and new data on the impact on cardiovascular outcomes of some of the new drugs (e.g., DDP-4 inhibitors and SGLT-2 inhibitors) have been published. The Canadian Diabetes Association also recently released an interim focused update of their clinical practice guidelines for the pharmacologic management of type 2 diabetes.5 There is therefore a need to determine the comparative effectiveness of new drugs for the treatment of patients with type 2 diabetes.

Of note, this evaluation will be done within the policy context currently prevailing in Canadian publicly funded drug programs for the reimbursement of drugs for type 2 diabetes. As such, this review will include assessment of second-line therapies (Table 1, Table 2). Third-line therapies will be assessed in a separate report.

Table 1: Oral Drugs Currently Available in Canada That Are Relevant to This Therapeutic Review

Drug Class Drug (Trade Name and Manufacturer)
Single Drug Products
DPP-4 Inhibitors Alogliptin
(Nesina, Takeda Canada Inc.)
Linagliptin
(Trajenta, Boehringer Ingelheim Canada Ltd.)
Saxagliptin
(Onglyza, AstraZeneca Canada Inc.)
Sitagliptin
(Januvia, Merck Canada Inc.)
 SGLT-2 Inhibitors Canagliflozin
(Invokana, Janssen Inc.)
Dapagliflozin
(Forxiga, AstraZeneca Canada Inc.)
Empagliflozina
(Jardiance, Boehringer Ingelheim Canada Ltd.)
Sulfonylureas Chlorpropamide
(Generic products only)
Gliclazideb
(Diamicron, Diamicron MR, Servier Canada Inc.)
Glimepiride b
(Amaryl, Sanofi-Aventis Canada Inc.)
Glyburide b
(Diabeta, Sanofi-Aventis Canada Inc.)
Tolbutamide
(Generics products only)
Fixed-Dose Combination Drug Products
DPP-4 Inhibitors/Biguanides Alogliptin/metformin
(Kazano, Takeda Canada Inc.)
Linagliptin/metformin
(Jentadueto, Boehringer Ingelheim Canada Ltd.)
Saxagliptin/metformin
(Komboglyze, AstraZeneca Canada Inc.)
Sitagliptin/metformin
(Janumet, Janumet XR, Merck Canada Inc.)
SGLT-2 Inhibitors/Biguanides Dapagliflozin/metformin
(Xigduo, AstraZeneca Canada Inc.)
Empagliflozin/metformin
(Synjardy, Boehringer Ingelheim (Canada) Ltd.)
Canagliflozin/metformin
(Product name TBC, Janssen Inc.)c

DPP-4 = dipeptidyl peptidase-4; SGLT-2 = sodium-glucose cotransporter-2; TBC = to be confirmed.

Notes:

  1. Table adapted from Table 8 in Endocrine and Metabolic Disorders: Diabetes Mellitus Chapter of Therapeutic Choices. Canadian Pharmacists Association, 2015. All rights reserved. Source: https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0079#tablc0079n00043. Accessed: July 29, 2015.
  2. Other information sources include Product Monograph available from the Health Canada Drug Product Database (http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php) as well as CADTH 2013 (Updated) Optimal Use Reports on the optimal use of second- and third line therapies for type 2 diabetes mellitus (https://www.cadth.ca/second-third-line-therapies-type-2-diabetes).
    a Not included in Therapeutic Choices.
    b Generic products also available.
    c Pre-Notice of Compliance CADTH Common Drug Review submission received on February 3, 2016 (https://www.cadth.ca/canagliflozin-and-metformin-hydrochloride).

Table 2: GLP-1 Analogues, Insulin and Insulin Analogues Available in Canada

GLP-1 Analogue Products
Dulaglutide (Trulicity, Eli Lilly Canada Inc.)
Exenatide (Byetta, AstraZeneca Canada Inc.)
Exenatide extended-release (Bydureon, AstraZeneca Canada Inc.)
Liraglutide (Victoza, Novo Nordisk Canada Inc.)
Albiglutide (Eperzan, GlaxoSmithKline Inc.)
Insulin and Insulin Analogue Productsa Insulin and Insulin Analogue Types
Insulin aspart (NovoRapid) Very rapid-acting insulin analogue
Insulin glulisine (Apidra) Very rapid-acting insulin analogue
Insulin lispro (Humalog) Very rapid-acting insulin analogue
Insulin, regular (Humulin R, Novolin ge Toronto) Rapid-acting insulin
Insulin, pork (Hypurin Regular) Rapid-acting insulin
Insulin, NPH (Humulin N, Novolin ge NPH) Intermediate-acting insulin
Insulin, pork (NPH/Hypurin NPH) Intermediate-acting insulin
Insulin detemir (Levemir) Long-acting insulin analogue
Insulin glargine (Lantus, Toujeo, Basaglar) Long-acting insulin analogue
Insulin regular/insulin, NPH
(Humulin 30/70, Novolin ge 30/70, 40/60, 50/50)
Mixed (regular/NPH) human insulin
Insulin lispro/lispro protamine
(Humalog Mix25, Humalog Mix50)
Mixed insulin analogue
Insulin aspart/aspart protamine (NovoMix 30) Mixed insulin analogue

GLP-1 = glucagon-like peptide-1; NPH = neutral protamine Hagedorn.
Source of information: Therapeutic Choices. Canadian Pharmacists Association, 2015. [Source: https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0079#tablc0079n00043 ; Accessed; July 29 2015 (proprietary)]
Note: Insulin and insulin analogue products include subsequent entry biologics.
a All concentrations of insulin and insulin analogue products will be considered, if appropriate (e.g., insulin glargine 100 units/mL and 300 units/mL; insulin lispro 100 units/mL and 200 units/mL).

 

Scope and Protocol Development

To inform the final scope of the therapeutic review and protocol development, a proposed scope was posted to the CADTH website for stakeholder feedback (www.cadth.ca) following review with CADTH jurisdictional clients. Patient-group input was also solicited.

 

Deliverables

The following deliverables are planned:

  •  A Science Report, including an updated systematic review of the comparative efficacy and safety of second-line antidiabetic drugs for the treatment of type 2 diabetes mellitus. The Science Report will also report the findings of the any new research questions related to the comparative cardiovascular effects of the antidiabetic agents.
  • An Economics Report, including cost-effectiveness analyses for second-line therapy, based on updated clinical results.
  • A CADTH Canadian Drug Expert Committee (CDEC) Recommendation document based on the Science and Economic Reports and stakeholder feedback.

Note that CDEC will develop recommendations only for new drugs available for the second-line treatment of patients with type 2 diabetes; i.e., DPP-4 inhibitors, GLP-1 analogues, and SGLT-2 inhibitors. Supplemental research questions will be reported in accompanying documents or appendices.

 

Policy Questions

There is one policy question for this review. The policy question reflects the needs of CADTH jurisdictional clients. This question will also inform the deliberations of the CDEC members when they develop the Therapeutic Review Recommendation document.

  1. What is/are the preferred second-line agent(s) to consider for the treatment of adults with type 2 diabetes with inadequate glycemic control on metformin monotherapy?

 

Research Questions

The research questions for this project are presented below. These reflect the information needs to CADTH jurisdictional clients with regard to comparative efficacy, safety, and cost. These questions will form the basis of the primary clinical and economic evaluations.

  1. For adults with type 2 diabetes on metformin monotherapy with inadequate glycemic control, what is the comparative efficacy and safety of using a drug from one of the following classes as second-line agent:
    a. Sulfonylurea
    b. Insulin
    c. DPP-4 inhibitor
    d. GLP-1 analogue
    e. SGLT-2 inhibitor?
     
  2. For adults with type 2 diabetes on metformin monotherapy with inadequate glycemic control, what is the comparative cost-effectiveness of using a drug from one of the following classes as second-line agent:
    a. Sulfonylurea
    b. Insulin
    c. DPP-4 inhibitor
    d. GLP-1 analogue
    e. SGLT-2 inhibitor?
     
  3. For adults with type 2 diabetes, what are the comparative cardiovascular effects of drugs belonging to one of the following classes:
    a. Insulin
    b. DPP-4 inhibitor
    c. GLP-1 analogue
    d. SGLT-2 inhibitor?
     

 

Practice Support Questions

The following questions will be part of a supplemental issue to the therapeutic review.

  1. What are patient characteristics associated with rejecting sulfonylureas and insulin as therapeutic alternatives in the treatment of type 2 diabetes?
  2. Are there any published criteria for adding a DDP-4 inhibitor, a GLP-1 analogue, or a SGLT-2 inhibitor to insulin for the treatment of patients with type 2 diabetes with inadequate glycemic control?

 

Systematic Review

Literature Search Strategy

The search strategy will be developed and tested through an iterative process by an experienced medical information specialist in consultation with the review team.

Published literature will be identified using a peer-reviewed search strategy by searching the following bibliographic database: Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, and Embase using the OVID platform, the Cochrane Central Register of Controlled Trials (CENTRAL) database on Wiley and PubMed for the most recent and unindexed citations only. Strategies will use a combination of controlled vocabulary (e.g., “Diabetes Mellitus, Type 2,” “Hypoglycemic Agents,” “and Dipeptidyl-Peptidase IV Inhibitors”) and keywords (e.g., “T2DM,” “anti-diabetic,” “DPP 4 inhibitors”). Vocabulary and syntax will be adjusted across databases. The 2008 sensitivity- and precision-maximizing version of the Cochrane highly sensitive search strategy will be used to identify randomized controlled trials. When possible, animal-only, pediatric-only, and opinion-pieces will be removed from the results. Retrieval will not be limited by publication year or language. Regular alerts will be established to update the search until recommendations by CDEC, based on this review, are finalized. See Appendix 1 for the detailed search strategies.

A grey literature search of clinical trial registries and other relevant trial sources will be conducted. The trial registry search will be limited to completed trials with results.

Selection and Eligibility Criteria

Study screening and selection will be conducted independently by two reviewers, with a third reviewer used to resolve disagreements.

RCTs will be eligible for inclusion if they meet the study design, population, intervention, and comparator criteria and outcomes of interest outlined in Table 3. Interventions of interest, including fixed-dose combinations and mixed insulin products are further detailed in Tables 1 and 2. Detailed eligibility criteria for studies are provided in Table 4. Studies will not be excluded based on outcomes reported. Weight-loss drugs (e.g., orlistat, sibutramine) included in previous CADTH reviews will not be included in this update. The primary role of such drugs is to lower body weight rather than to treat hyperglycemia.

Table 3: Population, Intervention, Comparator, Outcome, and Study Designs of Interest

Population For research questions 1 and 2: Adults with type 2 diabetes on pharmacotherapy with inadequate glycemic controla

For research question 3: Adults with type 2 diabetes
Interventionsb SGLT-2 inhibitors canagliflozin, dapagliflozin, empagliflozin
GLP-1 analogues dulaglutide, exenatide, liraglutide, albiglutide
DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin
Comparatorsb SGLT-2 inhibitors canagliflozin, dapagliflozin, empagliflozin
GLP-1 analogues dulaglutide, exenatide, liraglutide
DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin
Sulfonylureas  chlorpropamide, gliclazide, glimepiride, glyburide, tolbutamide
Insulin, insulin analogues, and insulin analogue biosimilars Regular insulin, pork insulin, insulin aspart, insulin lispro, insulin glulisine, insulin NPH, insulin detemir, insulin glargine, mixed regular insulin/insulin NPH, mixed insulin lispro/lispro protamine and mixed insulin aspart/aspart protamine (see Table 2)
Metformin  
Placebo  
Outcomes Clinical benefitsc
  • Composite of death from cardiovascular causes/non-fatal myocardial infarction/non-fatal stroke
  • Death from cardiovascular causes
  • Fatal and non-fatal myocardial infarction
  • Fatal and non-fatal stroke
  • Unstable angina
  • Hospitalization for unstable angina
  • Heart failure
  • Hospitalization for heart failure
  • Transient ischemic attack
  • Coronary revascularization procedure
  • Blood pressure
  • Body weightd
  • BMI
  • Hemoglobin A1C
  • Discontinuation of blood pressure medication
Clinical harms
  • Total adverse events
  • Serious adverse events
  • Withdrawals due to adverse events
Other notable harms
  • Hypoglycemia
  • Urogenital adverse events
  • Renal adverse events
  • Lipids
  • Ketoacidosis
  • Bone fractures
  • Bladder cancer
  • Pancreatitis
  • Pancreatic cancer

A1C = glycated hemoglobin; BMI = body mass index; DPP-4 = dipeptidyl peptidase-4; NPH = neutral protamine Hagedorn; SGLT-2 = sodium-glucose cotransporter-2; TBC = to be confirmed.
a In the previous CADTH reviews, inadequate control was defined as hemoglobin A1C > 6.5% or fasting plasma glucose > 7 mmol/L or two-hour post-prandial glucose > 10 mmol/L.
b Interventions may include regimens combining the above drugs with metformin, a sulfonylurea, insulin product and/or other drug (e.g., pioglitazone) as indicated in the Health Canada product monographs. Other agents (including meglitinides, alpha-glucosidase inhibitors, thiazolidinediones or insulin degludec) may also be included as comparators in the network meta-analysis.
c Based on a reduction in events, or a change in clinical measurement signifying improvement or clinical benefit.
d A decrease in weight will be considered a clinical benefit, while an increase in weight will be considered a harm.

Table 4: Detailed Selection Criteria for Randomized Controlled Trials

Inclusion Criteria

Studies Will Be Included If:

For all research questions

They report an active and/or placebo-controlled randomized controlled trial.

They are published in English.

For research questions

1 and 2

Study participants must have inadequately controlled type 2 diabetes and receive a second-line drug interest as an add-on to, or switches from, metformin monotherapy or a combination of metformin and another intervention of interest. This includes studies that employ a metformin monotherapy run-in period prior to the addition of study interventions.

Studies where adults with type 2 diabetes require alternative hypoglycemic therapy due to intolerance of current therapy will also be included.

Studies will be included regardless of metformin dosage at baseline or treatment history prior to the metformin.

For research question 3

Eligible study participants must have type 2 diabetes and be receiving one of the eligible interventions of interest and that report cardiovascular endpoints as a primary outcome.

Exclusion Criteria

Studies will be excluded if:

For all research questions

Treatment duration is less than 4 weeks.

Language of full-text publication is not English.

They are reported only in abstract format.

For research questions 1 and 2

Second-line antidiabetes drugs added to metformin monotherapy were compared with switching to second-line therapy (i.e., discontinuation of metformin monotherapy).

Switch from metformin to another antidiabetes drug(s) was compared with switch to placebo or no therapy (i.e., no active comparator).

More than 15% of the patients used a drug other than metformin monotherapy at baseline and no results were reported for the subgroup of metformin users.

Data Extraction and Critical Appraisal

Data extraction will be performed using data extraction forms designed a priori. The internal and external validity of randomized controlled trials will be assessed using the SIGN 50 checklist as a guide.6 Both data extraction and validity assessment will be performed by one reviewer, and verified by a second reviewer. Any disagreements will be resolved by consensus when possible; otherwise, the judgment of a third reviewer will be considered final.

This update will assess outcomes that were not previously evaluated in CADTH reviews (e.g., body mass index and blood pressure). Included studies from the previous CADTH reviews will be re-screened for these outcomes. For research question 3, eligible studies must report cardiovascular outcomes of interest to this review as a primary outcome.

Data Synthesis and Analysis

The network meta-analyses (NMAs) from the previous CADTH second-line type 2 diabetes review will be updated with data from the newly identified trials. The methodology employed will be consistent with the previous CADTH reviews. WinBUGS software version 1.4.3 (MRC Biostatistics Unit, Cambridge, UK) will be used for the Bayesian NMAs using a binomial likelihood model for dichotomous outcomes or a normal likelihood model for continuous outcomes developed at the Universities of Bristol and Leicester.7 Metformin monotherapy or the addition of placebo to metformin will be the default reference group for the NMAs.

Point estimates and 95% credible intervals (odds ratio for dichotomous outcomes, mean difference for continuous outcomes) will be estimated using Markov Chain Monte Carlo methods and basic parameters of the treatment effects in the model will be assigned vague prior distributions. Both fixed- and random-effects NMAs will be conducted; assessment of model fit and choice of model will be based on the assessment of the deviance information criterion (DIC) and comparison of residual deviance to number of unconstrained data points. Model diagnostics including trace plots and the Brooks–Gelman–Rubin statistic will be considered to assess model convergence. Three chains will be fit into WinBUGS for each analysis, each employing ≥ 10,000 iterations, with a burn-in of ≥ 10,000 iterations.8-11

Inconsistency between direct evidence and indirect evidence will be formally assessed by comparing the deviance and DIC statistics of the consistency and inconsistency models. To help identify the loops in which inconsistency is present, the posterior mean deviance of the individual data points in the inconsistency model will be plotted against their posterior mean deviance in the consistency model.

Frequentist pairwise meta-analysis will be performed using RefMan. A random-effects model will be used for the reference case in all pairwise meta-analyses and NMAs. The robustness of the reference case was assessed using alternative modelling, sensitivity analyses, and meta-regressions (when data are sufficient).12

As in the previous CADTH second-line type 2 diabetes reviews, three different evidence networks are planned:

  • Drug-class level network (anticipated reference case)
  • Dose-stratified network
  • Individual-drug network.

The anticipated reference case analysis will be based on a drug-class level network in which moderate to high fixed-dose and titrated-dose studies are pooled into a single node, and low fixed-dose studies are excluded.

Low doses will be defined as those being below the World Health Organization Defined Daily Dose (DDD).13

To account for differences in dosing across studies and avoid exclusion of the low-dose data, a dose-stratified model is planned in which each class of drug is stratified into three separate nodes representing distinct dosing strategies in the evidence network:

  • Individually titrated dosing 
  • Moderate to high fixed doses (i.e., dosing ≥ DDD)
  • Low fixed doses (i.e., dosing < DDD).

A third network model of individual drugs is also planned. Each class will be separated into their respective individual drugs.

The reference case for cost-effectiveness analysis is anticipated to be performed using the results of the class-level model, although some results from the dose-stratified or individual models may be used to inform certain sensitivity analyses.

Sensitivity analyses will be conducted by removing studies:

  • of poor methodological quality
  • employing a crossover design
  • of less than one year’s duration (and less than three months’ duration for the A1C outcome)
  • where patients used less than 1,500 mg/day of metformin at baseline
  • that tested drugs currently not available in Canada.

For outcomes where NMA is appropriate and feasible, meta-regression analyses or subgroup analyses will be carried out to account for differences in baseline A1C, duration of diabetes, and baseline body mass index (for the body weight outcome only) and different study designs (superiority versus inferiority trial). For research question 3, only trials aiming to evaluate cardiovascular end points as primary outcomes will be included in related analyses.

 

Pharmacoeconomic Review

Cost-utility analyses will be conducted for second-line treatments for type 2 diabetes. For second-line therapy, the key comparisons in the analysis will be of metformin plus sulfonylureas, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 analogues, or insulins versus metformin alone. All analyses will be performed at the class level and will be based on the lowest publicly available price for drugs within each class.

The analyses will be conducted using an updated version of the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (v2.0) that was previously used in CADTH assessments of diabetes therapies. The newer UKPDS Outcomes Model will be updated to reflect the most current clinical evidence, utility estimates for modelled health states, drug prices, and costs for management of complications. The primary perspective will be that of the Canadian publicly funded health care system. The results of the analyses will be presented as incremental cost-utility ratios (ICURs) based on the cost per quality-adjusted life-year (QALY) gained. A lifetime horizon will be used for the cost-utility analyses.

The clinical systematic review and NMA will inform the clinical inputs for the cost-utility analysis: treatment efficacy, patient baseline clinical characteristics and history of complications, and incidence of complications related to type 2 diabetes will be obtained from the clinical review. Health-related quality of life estimates will be derived from the published literature; costs will be obtained from the published literature, publicly available sources of Canadian costs, or expert opinion if needed.

One-way sensitivity and scenario analyses will be conducted to assess the effects of uncertainty in the model parameters and robustness of results. Depending upon the data available, the sensitivity analyses may examine uncertainty in parameters such as the estimates of clinical disutility associated with hypoglycemia (mild, moderate, and severe) and weight gain, treatments costs, baseline rates of adverse events, risk of long-term complications associated with type 2 diabetes, or time horizon. Probabilistic sensitivity analyses will also be performed to assess the impact of uncertainty in model inputs on cost-effectiveness results.

 

References

  1. Second-line therapy for patients with diabetes inadequately controlled on metformin: a systematic review and cost-effectiveness analysis [Internet]. Ottawa: CADTH; 2010 Aug. [cited 2016 Jun 17]. (CADTH optimal use report; vol.4, no.2). Available from: https://www.cadth.ca/sites/default/files/pdf/C1110_SR_Report_final_e.pdf
  2. Clinical review: third-line therapy for patients with type 2 diabetes inadequately controlled with metformin and a sulfonylurea [Internet]. Ottawa: CADTH; 2010 Aug. [cited 2016 Jun 17]. (CADTH therapeutic review). Available from: https://www.cadth.ca/sites/default/files/pdf/Diabetes_TR_Clinical_Report_Final_e.pdf
  3. Third-line pharmacotherapy for type 2 diabetes — update [Internet]. Ottawa: CADTH; 2013 Jul. [cited 2016 Jun 17]. (CADTH optimal use report; vol.3, no.1b). Available from: https://www.cadth.ca/sites/default/files/pdf/OP0512_Diabetes%20Update_Third-line_e.pdf
  4. Second-line pharmacotherapy for type 2 diabetes — update [Internet]. Ottawa: CADTH; 2013 Jul. [cited 2016 Jun 17]. (CADTH optimal use report; vol.3, no.1a). Available from: https://www.cadth.ca/sites/default/files/pdf/OP0512_DiabetesUpdate_Second-line_e.pdf
  5. Pharmacologic management of type 2 diabetes: 2016 interim update. Can J Diabetes [Internet]. 2016 Jun [cited 2016 Jun 17];40(3):193-5. Available from: http://guidelines.diabetes.ca/Browse/Chapter13_2016
  6. Scottish Intercollegiate Guidelines Network (SIGN). SIGN 50: a guideline developer's handbook [Internet]. Edinburgh: SIGN; 2015 Nov. [cited 2016 Jun 17]. Available from: http://www.sign.ac.uk/pdf/sign50.pdf
  7. Spielgelhalter D, Thomas A, Best N, Lunn D. WinBUGS user manual [Internet]. Version 1.4. Cambridge (GB): MRC Biostatistics Unit; 2003. [cited 2016 Jun 17]. Available from: http://www.mrc-bsu.cam.ac.uk/wp-content/uploads/manual14.pdf
  8. Cooper NJ, Sutton AJ, Morris D, Ades AE, Welton NJ. Addressing between-study heterogeneity and inconsistency in mixed treatment comparisons: Application to stroke prevention treatments in individuals with non-rheumatic atrial fibrillation. Stat Med. 2009 Jun 30;28(14):1861-81.
  9. Dias S, Welton N, Sutton A, Caldwell DM, Lu G, Ades AE. Inconsistency in networks of evidence based on randomised controlled trials [Internet]. Sheffield (GB): NICE DSU Decision Support Unit; 2011 May. [cited 2016 Jun 17; updated 2014 Apr]. (Technical support document 4). Available from: http://www.nicedsu.org.uk/TSD4%20Inconsistency.final.15April2014.pdf
  10. Heterogeneity: subgroups, meta-regression, bias and bias-adjustment [Internet]. Sheffield (GB): NICE Decision Support Unit; 2011 Sep. [cited 2016 Jun 17; updated 2012 Sep]. (Technical support document 3). Available from: http://www.nicedsu.org.uk/TSD3%20Heterogeneity.final%20report.08.05.12.pdf
  11. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med. 2010 Mar 30;29(7-8):932-44.
  12. Dias S, Sutton AJ, Welton NJ, Ades AE. Evidence synthesis for decision making 3: heterogeneity--subgroups, meta-regression, bias, and bias-adjustment. Med Decis Making. 2013 Jul;33(5):618-40.
  13. Defined daily dose: definition and general considerations [Internet]. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2009 Dec 17. [cited 2016 Jun 17]. Available from: http://www.whocc.no/ddd/definition_and_general_considera/

 

Appendix 1 — Literature Search Strategy

Type 2 DM
Final Strategies
2016 Mar 5

OVID Multifile
Database: Embase Classic+Embase <1947 to 2016 March 04>, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1946 to Present>
Search Strategy:

--------------------------------------------------------------------------------

1 exp Diabetes Mellitus, Type 2/ (266330)
2 Diabetes Mellitus/ (557998)
3 ((adult or ketosis-resistant or matur* or late or non-insulin depend* or noninsulin depend* or slow or stable or type 2 or type II or lipoatrophic) adj3 diabet*).tw,kw. (275289)
4 (MODY or NIDDM or T2DM).tw,kw. (45223)
5 or/1-4 (845937)
6 exp Diabetes Mellitus, Type 2/dt (66593)
7 Drug Combinations/ (114030)
8 Drug Therapy, Combination/ (196166)
9 6 and (7 or 8) (3517)
10 Hypoglycemic Agents/ (81238)
11 (antidiabetic? or anti-diabetic? or antihyperglyc?emic? or anti-hyperglyc?emic? or hypoglyc?emic? or antidiabetes or anti-diabetes).tw,kw. (89934)
12 Dipeptidyl-Peptidase IV Inhibitors/ (5438)
13 ((DPP4 or DPP 4 or DPP IV) adj1 inhibitor?).tw,kw. (5838)
14 (dipeptidyl-peptidase IV adj2 inhibitor?).tw,kw. (1193)
15 (dipeptidyl-peptidase 4 adj2 inhibitor?).tw,kw. (2749)
16 gliptin?.tw,kw. (406)
17 (alogliptin or nesina or SYR 322 or SYR322 or HSDB 8203 or incresina or vipidia).tw,kw. (800)
18 JHC049LO86.rn. (139)
19 Linagliptin/ (1411)
20 (linagliptin or BI 1356 or ONDERO or tradjenta or trajenta or trayenta or trazenta).tw,kw. (1182)
21 3X29ZEJ4R2.rn. (192)
22 (saxagliptin or BMS 477118 or BMS477118 or HSDB 8199 or Onglyza or OPC 262).tw,kw. (1331)
23 9GB927LAJW.rn. (202)
24 exp Sitagliptin Phosphate/ (6074)
25 (sitagliptin or EC 690-730-1 or Glactiv or HSDB 7516 or januvia or "mk 0431" or mk0431 or mk 431 or ono 5435 or ristaben or sitagliptine or tesabel or tesavel or xelevia).tw,kw. (4518)
26 TS63EW8X6F.rn. (808)
27 Sodium-Glucose Transporter 2/ai (514)
28 (sodium-glucose transporter 2 inhibitor? or sodium-glucose cotransporter 2 inhibitor?).tw,kw. (420)
29 (sodium-glucose transporter 2 inhibitor? or sodium-glucose co-transporter 2 inhibitor?).tw,kw. (392)
30 ((SGLT-2 or SGLT2) adj inhibitor?).tw,kw. (1855)
31 (sodium dependent glucose transporter 2 inhibitor? or sodium dependent glucose cotransporter 2 inhibitor?).tw,kw. (23)
32 (sodium dependent glucose transporter 2 inhibitor? or sodium dependent glucose co-transporter 2 inhibitor?).tw,kw. (14)
33 gliflozin?.tw,kw. (44)
34 Canagliflozin/ (916)
35 (canagliflozin or Invokana or JNJ 24831754* or JNJ 28431754 or TA 7284 or Prominad).tw,kw. (859)
36 0SAC974Z85.rn. (141)
37 (dapagliflozin or BMS 512148 or BMS512148 or edistride or forxiga or farxiga).tw,kw. (1079)
38 1ULL0QJ8UC.rn. (0)
39 (empagliflozin or BI 10773 or BI10773 or Jardiance).tw,kw. (645)
40 HDC1R2M35U.rn. (108)
41 Sulfonylurea Compounds/ (12899)
42 (sulfonylurea? or sulfonurea? or sulfonyl urea? or sulfonylcarbamide? or sulphonurea? or sulphonylurea?).tw,kw. (21551)
43 Chlorpropamide/ (7986)
44 (adiaben or apo-chlorpropamide or apochlorpropamide or abemide or "arodoc c" or asucrol or ascurol or biabenal or bioglumin or BRN 2218363 or catanil or CCRIS 155 or chlomide or chlormide or chlorodiabina or chloropropamide or chlorpromide or clorpropamide or copamide or chloronase or chlorpromide or clorpropamide or chloropropamide or chlorpropamid or chlorpropamide or chlorpropamidum or clorpropamid or clorpropamida).tw,kw. (3523)
45 (dabinese or deavynfar or diabaril or diabechlor or diabeedol or diabemide or diabenal or diabenese or diabeneza or diabet-pages or diabetoral or diabexan or diabiclor or diabines or diabinese or diabitex or diabitol or diamel ex or dibecon or dynalase or EINECS 202-314-5 or eubetin or glicoben or glisema or glucamide or glycemin or glymese or HSDB 2051 or hypomide or insilange or insogen or insulase).tw,kw. (732)
46 (melormin or meldian or melitase or mellinese or millinese or NCI-C01752 or NSC 44634 or NSC 626720 or neo-toltinon or oradian or P 607 or pamidin or prodiaben or pubetin or stabinol or tesmel or "p chlorobenzolsulphonylglycolic acid nitrile" or para chlorobenzenesulfonylglycolic acid nitrile or parachlorobenzene sulfonylglycolic acid nitrile or U-3818 or U-9818).tw,kw. (172)
47 WTM2C3IL2X.rn. (1810)
48 Gliclazide/ (5655)
49 (gliclazide or diaglyk or diaikron or diabrezide or diamicron or BRN 1657836 or EINECS 244-260-5 or gen-gliclazide or gliklazid or gliclazida or gliclazidum or glimicron or glyade or glyclazide or glycazide or nordialex or predian or S 1702 or S 852 or SE 1702).tw,kw. (3352)
50 G4PX8C4HKV.rn. (767)
51 (glimepiride or amaryl or amarel or BRN 5365754 or CCRIS 7083 or endial or euglim or glemax or glimepirid or glimepirida or glimepiridum or glimerid or glorion or HOE 490 or HOE490 or solosa or "s 80 8490").tw,kw. (3176)
52 6KY687524K.rn. (658)
53 Glyburide/ (27473)
54 (adiab or amecladin or apo-glibenclamide or azuglucon or bastiverit or benclamin or betanase or betanese 5 or BRN 2230085 or calabren or clamide or clibenclamide or cytagon or dangbinol or daonil or debtan or diabasan or diabeta or dibelet or duraglucon or EINECS 233-570-6 or euclamin or euglucan or euglucon or euglykon).tw,kw. (1292)
55 (GBN 5 or gen-glybe or gewaglucon or gilemal or glamide or glencamide or gliban or glibeclamid or glibemid or gliben or glibenbeta or glibenclamid or glibenclamida or glibenclamide or glibenclamidum or glibenhexal or glibenil or glibens or glibesyn or glibet or glibetic or glibil or gliboral or glicem or glidiabet or gliformin or glikeyer or glimel or glimide or glimidstada or glisulin or glitisol or glubate or gluben).tw,kw. (17385)
56 (glucobene or glucohexal or glucolon or glucomid or gluconic or glucoremed or glucoven or glukoreduct or glulo or glyamid or glyben or glybencamidum or glybencenamide or glybenclamid or glybenclamide or glybendamine or glybenzyclamide or glybenzcyclamide or glyburide or glycolande or glycomin or glynase or HB 419 or HB 420 or hemi-daonil or hexaglucon or humedia or insol or lederglib or libanil or lisaglucon or locose or lodulce).tw,kw. (6708)
57 (maninil or manoglucon or med-glionil or melix or micronase or miglucan or nadib or neogluconin or norglicem 5 or normoglucon or orabetic or pira or praeciglucon or prodiabet or renabetic or RP-1127 or semi-daonil or semi-euglucon or semi-gliben-puren n or sugril or suraben or tiabet or U 26452 or U-26 452 or UR 606 or yuglucon or xeltic).tw,kw. (680)
58 SX6K58TVWC.rn. (5768)
59 Tolbutamide/ (18758)
60 (abemin or aglicem or aglicid or aglycid or apo-tolbutamide or arcosal or arkozal or artosin or artosina or artozin or beglucin or BRN 1984428 or butamid or butamide or butamidum or CCRIS 592 or "D 860" or diabecid or diaben or diabenyl or diabeton or diabesan or diasulfon or diabetamid or diabetol or diabuton or diatol or dirastan or diasulin or diaval or dolipol or drabet).tw,kw. (630)
61 (EINECS 200-594-3 or fresan or glicemin or glicotron or glycotron or guabeta or glyconon or HLS 831 or HSDB 3393 or hypoglycone or ipoglicone or ipoglucos or mermol or metil glucosulfina or mobenol or NCI-C01763 or NSC 23813 or neo antiglycemikos or neo diabetal or neo norboral or neobellin or neoinsoral).tw,kw. (29)
62 (orabet or oralin or oresan or orezan or orinade or orinase or orinaz or orsinon or osdiabet or oterben or pramidex or proinsul or rastinon or SK-tolbutamide or tarasina or tobutamine or tol ortab or tolbet or tolbugen or tolbusal or tolbutamid or tolbutamida or tolbutamide or tolbutamidum or tolbutone or tolbutamte or tolbutol or tolbutylharnstoff or tolbutylurea or tolglybutamide or tolsiran or tolubetin or toluran or tolurast or tosula or toluina or tolumid or toluvan or tolylsulfonylbutylurea or "U 2043" or willbutamide).tw,kw. (11849)
63 982XCM1FOI.rn. (5177)
64 Thiazolidinediones/ (20146)
65 (thiazolidinedione* or TZD or TZDs).tw,kw. (12397)
66 (pioglitazone* or actos or AD 4833 or piomed or U 72107A or U72 107A or cereluc or glidipion or glita or glitase or glustin or paglitaz or pioglit or sepioglin or zactos).tw,kw. (11333)
67 X4OV71U42S.rn. (2980)
68 (rosiglitazone* or avandia or BRL 49653-C or BRL 49653 or nyracta or rezult or rossini or venvia).tw,kw. (12978)
69 05V02F2KDG.rn. (3774)
70 exp Glucagon-Like Peptide 1/aa (980)
71 ((glucagon-like peptide-1 or GLP-1 or GLP1 or GLP-1R or GLP1R) adj2 analog*).tw,kw. (2996)
72 Glucagon-Like Peptide-1 Receptor/ (3946)
73 ((glucagon-like peptide-1 or GLP-1 or GLP1 or GLP-1R or GLP1R) adj2 (receptor? or protein?)).tw,kw. (7207)
74 Receptors, Glucagon/ag (716)
75 ((glucagon-like peptide-1 or GLP-1 or GLP1 or GLP-1R or GLP1R) adj2 agonist*).tw,kw. (5289)
76 incretin mimetic*.tw,kw. (754)
77 (dulaglutide or LY-2189265 or LY2189265 or trulicity).tw,kw. (315)
78 WTT295HSY5.rn. (34)
79 (AC 2993 or AC 2993A or AC-2993 or AC002993 or AC2993 or AC2993A or baietta or byetta or bydureon or DA 3091 or exenatide or exendin 4 or HSDB 7789 or LY 2148568 or LY2148568 or PT302 or Ex4 peptide or ITCA 650).tw,kw. (7065)
80 9P1872D4OL.rn. (1654)
81 Liraglutide/ (4905)
82 (liraglutida or liraglutide or liraglutidum or HSDB 8205 or NN-2211 or NN2211 or NNC 90-1170 or saxenda or victoza).tw,kw. (3920)
83 839I73S42A.rn. (697)
84 Insulin, Long-Acting/ (4078)
85 ((long-acting or LA or semilente or semi-lente or slow* acting or intermediate-acting) adj (insulin* or analog*)).tw,kw. (3627)
86 Insulin Detemir/ (3156)
87 (detemir or determir or levemir or NN-304 or NN304).tw,kw. (2636)
88 4FT78T86XV.rn. (432)
89 Insulin Glargine/ (8182)
90 (abasaglar or abasria or basaglar or glargine or HOE-901 or HOE901 or lantus or ly 2963016 or ly2963016 or optisulin or toujeo).tw,kw. (6280)
91 2ZM8CX04RZ.rn. (1259)
92 exp Insulin, Short-Acting/ (1999)
93 ((fast-acting or quick-acting or short-acting or rapid* acting) adj (insulin? or analog*)).tw,kw. (3052)
94 (insulin aspart* or (B28 adj1 insulin?) or (B28 adj1 insulin?) or (B28asp* adj1 insulin?) or NovoLog* or NovoMix* or Novo Mix* or NovoRapid*).tw,kw. (3086)
95 D933668QVX.rn. (528)
96 (lispro or lyspro or humalog or liprolog).tw,kw. (3712)
97 (apidra or glulisine).tw,kw. (1017)
98 7XIY785AZD.rn. (132)
99 exp Insulin, Isophane/ (7864)
100 (actraphan? or berlinsulin or "humulin i" or "humulin n" or insulatard or (insulin? adj3 monotard) or isophane or (insulin? adj2 NPH) or (insulin? adj2 protamine) or isofane or isophan or isophane or isophone or mixtard or novolin or nph iletin or nph umuline or orgasuline or protaphan or protaphane or protophane or prozinc or (zinc adj2 insulin?) or (zinc adj1 protamine)).tw,kw. (6799)
101 2ZM8CX04RZ.rn. (1259)
102 exp Insulin/ (461486)
103 (insulin? adj1 regular).tw,kw. (2886)
104 (insulin? adj1 human).tw,kw. (12859)
105 (nph insulin? or humulin or novolin).tw,kw. (4347)
106 ((insulin? adj1 (pork or porcine or pig or pigs)) or hypurin).tw,kw. (2880)
107 (alogliptin adj3 metformin).tw,kw. (27)
108 (metformin adj2 nesina).tw,kw. (0)
109 (kazano or nesimet or nesina or nesinamet or vipdomet).tw,kw. (80)
110 (linagliptin adj2 metformin).tw,kw. (72)
111 (jentadueto or trajenta duo or trajentamet or trayebta duo or trayenta duo).tw,kw. (28)
112 (saxagliptin adj3 metformin).tw,kw. (135)
113 (komboglyze or kombiglyze or comboglyze or duoglyze).tw,kw. (35)
114 "Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination"/ (5)
115 (sitagliptin adj3 metformin).tw,kw. (459)
116 (janumet or efficib or gliptamet or Januet or ristfor or velmetia or mk 0431a).tw,kw. (169)
117 (metformin adj3 dapagliflozin).tw,kw. (70)
118 (ebymect or xigduo).tw,kw. (20)
119 (empagliflozin adj3 metformin).tw,kw. (22)
120 (jardiamet or jardiancemet or synjardy).tw,kw. (3)
121 (metformin adj3 rosiglitazone).tw,kw. (817)
122 (avandamet or interac).tw,kw. (308)
123 Glycoside Hydrolase Inhibitors/ (2932)
124 ((alpha-amylase or alpha-glucosidase or glucosidase or glycoside) adj2 inhibitor?).tw,kw. (6829)
125 Acarbose/ (7337)
126 (acarbose or ag 5421 or ag5421 or alpha ghi or bay g 5421 or bay g5421 or glibose or glicobase or glucobay or gluconase or glucor or glumida or prandase or precise or rebose).tw,kw. (307456)
127 T58MSI464G.rn. (1139)
128 (hb 699 or hb699 or meglitinide?).tw,kw. (642)
129 (actulin or ag ee 388 or ag ee388 or ag ee 623 or ag ee623 or enyglid or gluconorm or novonorm or prandin or rapilan or repaglinide or sestrine).tw,kw. (1882)
130 (a 4166 or a4166 or ay 4166 or ay4166 or djn 608 or djn608 or fasticor or glinate or nateglinide or sdz djn 608 or sdz djn608 or senaglinide or starlix or starsis or trazec or "ym 026").tw,kw. (1413)
131 (bay 1099 or bay m 1099 or bay m1099 or bay1099 or diastabol or glyset or miglitol or plumarol).tw,kw. (855)
132 0V5436JAQW.rn. (194)
133 (ao 128 or ao128 or basen or "en 116 077" or en 116077 or "en116 077" or en116077 or glustat or voglibose).tw,kw. (713)
134 or/9-133 (943368)
135 5 and 134 (232691)
136 (controlled clinical trial or randomized controlled trial).pt. (493183)
137 clinical trials as topic.sh. (175057)
138 (randomi#ed or randomly or RCT$1 or placebo*).tw. (1662366)
139 ((singl* or doubl* or trebl* or tripl*) adj (mask* or blind* or dumm*)).tw. (328932)
140 trial.ti. (349371)
141 or/136-140 (2094448)
142 135 and 141 (27582)
143 exp Animals/ not (exp Animals/ and Humans/) (13903716)
144 142 not 143 (18521)
145 Adolescent/ not (exp Adult/ and Adolescent/) (1002401)
146 exp Child/ not (exp Adult/ and exp Child/) (2892676)
147 exp Infant/ not (exp Adult/ and exp Infant/) (1546227)
148 or/145-147 (3676743)
149 144 not 148 (18221)
150 (comment or editorial or interview or news or newspaper article).pt. (1628874)
151 (letter not (letter and randomized controlled trial)).pt. (1826480)
152 149 not (150 or 151) (17868)
153 152 use prmz (9578)
154 diabetes mellitus/ (557998)
155 non insulin dependent diabetes mellitus/ (266146)
156 lipoatrophic diabetes mellitus/ (434)
157 ((adult or ketosis-resistant or matur* or late or non-insulin depend* or noninsulin depend* or slow or stable or type 2 or type II or lipoatrophic) adj3 diabet*).tw,kw. (275289)
158 (MODY or NIDDM or T2DM).tw,kw. (45223)
159 or/154-158 (845997)
160 non insulin dependent diabetes mellitus/dt (66555)
161 drug combination/ (55587)
162 160 and 161 (550)
163 antidiabetic agent/ (88027)
164 oral antidiabetic agent/ (15334)
165 (antidiabetic? or anti-diabetic? or antihyperglyc?emic? or anti-hyperglyc?emic? or hypoglyc?emic? or antidiabetes or anti-diabetes).tw,kw. (89934)
166 dipeptidyl peptidase IV inhibitor/ (7382)
167 ((DPP4 or DPP 4 or DPP IV) adj1 inhibitor?).tw,kw. (5838)
168 (dipeptidyl-peptidase IV adj2 inhibitor?).tw,kw. (1193)
169 (dipeptidyl-peptidase 4 adj2 inhibitor?).tw,kw. (2749)
170 gliptin?.tw,kw. (406)
171 alogliptin/ (980)
172 (alogliptin or nesina or SYR 322 or SYR322 or HSDB 8203 or incresina or vipidia).tw,kw. (800)
173 850649-62-6.rn. (464)
174 850649-61-5.rn. (838)
175 linagliptin/ (1411)
176 (linagliptin or BI 1356 or ONDERO or tradjenta or trajenta or trayenta or trazenta).tw,kw. (1182)
177 668270-12-0.rn. (938)
178 saxagliptin/ (1825)
179 (saxagliptin or BMS 477118 or BMS477118 or HSDB 8199 or Onglyza or OPC 262).tw,kw. (1331)
180 361442-04-8.rn. (1522)
181 945667-22-1.rn. (1455)
182 sitagliptin/ (6073)
183 (sitagliptin or EC 690-730-1 or Glactiv or HSDB 7516 or januvia or "mk 0431" or mk0431 or mk 431 or ono 5435 or ristaben or sitagliptine or tesabel or tesavel or xelevia).tw,kw. (4518)
184 486460-32-6.rn. (4204)
185 sodium glucose cotransporter 2 inhibitor/ (702)
186 (sodium-glucose transporter 2 inhibitor? or sodium-glucose cotransporter 2 inhibitor?).tw,kw. (420)
187 (sodium-glucose transporter 2 inhibitor? or sodium-glucose co-transporter 2 inhibitor?).tw,kw. (392)
188 ((SGLT-2 or SGLT2) adj inhibitor?).tw,kw. (1855)
189 (sodium dependent glucose transporter 2 inhibitor? or sodium dependent glucose cotransporter 2 inhibitor?).tw,kw. (23)
190 (sodium dependent glucose transporter 2 inhibitor? or sodium dependent glucose co-transporter 2 inhibitor?).tw,kw. (14)
191 gliflozin?.tw,kw. (44)
192 canagliflozin/ (916)
193 (canagliflozin or invokana or JNJ 24831754* or JNJ 28431754 or TA 7284 or prominad).tw,kw. (859)
194 842133-18-0.rn. (540)
195 dapagliflozin/ (1020)
196 (dapagliflozin or BMS 512148 or BMS512148 or edistride or forxiga or farxiga).tw,kw. (1079)
197 461432-26-8.rn. (705)
198 empagliflozin/ (556)
199 (empagliflozin or BI 10773 or BI10773 or jardiance).tw,kw. (645)
200 864070-44-0.rn. (386)
201 sulfonylurea derivative/ (8351)
202 (sulfonylurea? or sulfonurea? or sulfonyl urea? or sulfonylcarbamide? or sulphonurea? or sulphonylurea?).tw,kw. (21551)
203 chlorpropamide/ (7986)
204 (adiaben or apo-chlorpropamide or apochlorpropamide or abemide or "arodoc c" or asucrol or ascurol or biabenal or bioglumin or BRN 2218363 or catanil or CCRIS 155 or chlomide or chlormide or chlorodiabina or chloropropamide or chlorpromide or clorpropamide or copamide or chloronase or chlorpromide or clorpropamide or chloropropamide or chlorpropamid or chlorpropamide or chlorpropamidum or clorpropamid or clorpropamida).tw,kw. (3523)
205 (dabinese or deavynfar or diabaril or diabechlor or diabeedol or diabemide or diabenal or diabenese or diabeneza or diabet-pages or diabetoral or diabexan or diabiclor or diabines or diabinese or diabitex or diabitol or diamel ex or dibecon or dynalase or EINECS 202-314-5 or eubetin or glicoben or glisema or glucamide or glycemin or glymese or HSDB 2051 or hypomide or insilange or insogen or insulase).tw,kw. (732)
206 (melormin or meldian or melitase or mellinese or millinese or NCI-C01752 or NSC 44634 or NSC 626720 or neo-toltinon or oradian or P 607 or pamidin or prodiaben or pubetin or stabinol or tesmel or "p chlorobenzolsulphonylglycolic acid nitrile" or para chlorobenzenesulfonylglycolic acid nitrile or parachlorobenzene sulfonylglycolic acid nitrile or U-3818 or U-9818).tw,kw. (172)
207 94-20-2.rn. (5862)
208 gliclazide/ (5655)
209 (gliclazide or diaglyk or diaikron or diabrezide or diamicron or BRN 1657836 or EINECS 244-260-5 or gen-gliclazide or gliklazid or gliclazida or gliclazidum or glimicron or glyade or glyclazide or glycazide or nordialex or predian or S 1702 or S 852 or SE 1702).tw,kw. (3352)
210 21187-98-4.rn. (4621)
211 glimepiride/ (5332)
212 (glimepiride or amaryl or amarel or BRN 5365754 or CCRIS 7083 or endial or euglim or glemax or glimepirid or glimepirida or glimepiridum or glimerid or glorion or HOE 490 or HOE490 or solosa or "s 80 8490").tw,kw. (3176)
213 93479-97-1.rn. (4884)
214 glibenclamide/ (27473)
215 (adiab or amecladin or apo-glibenclamide or azuglucon or bastiverit or benclamin or betanase or betanese 5 or BRN 2230085 or calabren or clamide or clibenclamide or cytagon or dangbinol or daonil or debtan or diabasan or diabeta or dibelet or duraglucon or EINECS 233-570-6 or euclamin or euglucan or euglucon or euglykon).tw,kw. (1292)
216 (GBN 5 or gen-glybe or gewaglucon or gilemal or glamide or glencamide or gliban or glibeclamid or glibemid or gliben or glibenbeta or glibenclamid or glibenclamida or glibenclamide or glibenclamidum or glibenhexal or glibenil or glibens or glibesyn or glibet or glibetic or glibil or gliboral or glicem or glidiabet or gliformin or glikeyer or glimel or glimide or glimidstada or glisulin or glitisol or glubate or gluben).tw,kw. (17385)
217 (glucobene or glucohexal or glucolon or glucomid or gluconic or glucoremed or glucoven or glukoreduct or glulo or glyamid or glyben or glybencamidum or glybencenamide or glybenclamid or glybenclamide or glybendamine or glybenzyclamide or glybenzcyclamide or glyburide or glycolande or glycomin or glynase or HB 419 or HB 420 or hemi-daonil or hexaglucon or humedia or insol or lederglib or libanil or lisaglucon or locose or lodulce).tw,kw. (6708)
218 (maninil or manoglucon or med-glionil or melix or micronase or miglucan or nadib or neogluconin or norglicem 5 or normoglucon or orabetic or pira or praeciglucon or prodiabet or renabetic or RP-1127 or semi-daonil or semi-euglucon or semi-gliben-puren n or sugril or suraben or tiabet or U 26452 or U-26 452 or UR 606 or yuglucon or xeltic).tw,kw. (680)
219 10238-21-8.rn. (20454)
220 tolbutamide/ (18758)
221 (abemin or aglicem or aglicid or aglycid or apo-tolbutamide or arcosal or arkozal or artosin or artosina or artozin or beglucin or BRN 1984428 or butamid or butamide or butamidum or CCRIS 592 or "D 860" or diabecid or diaben or diabenyl or diabeton or diabesan or diasulfon or diabetamid or diabetol or diabuton or diatol or dirastan or diasulin or diaval or dolipol or drabet).tw,kw. (630)
222 (EINECS 200-594-3 or fresan or glicemin or glicotron or glycotron or guabeta or glyconon or HLS 831 or HSDB 3393 or hypoglycone or ipoglicone or ipoglucos or mermol or metil glucosulfina or mobenol or NCI-C01763 or NSC 23813 or neo antiglycemikos or neo diabetal or neo norboral or neobellin or neoinsoral).tw,kw. (29)
223 (orabet or oralin or oresan or orezan or orinade or orinase or orinaz or orsinon or osdiabet or oterben or pramidex or proinsul or rastinon or SK-tolbutamide or tarasina or tobutamine or tol ortab or tolbet or tolbugen or tolbusal or tolbutamid or tolbutamida or tolbutamide or tolbutamidum or tolbutone or tolbutamte or tolbutol or tolbutylharnstoff or tolbutylurea or tolglybutamide or tolsiran or tolubetin or toluran or tolurast or tosula or toluina or tolumid or toluvan or tolylsulfonylbutylurea or "U 2043" or willbutamide).tw,kw. (11849)
224 64-77-7.rn. (12174)
225 2,4 thiazolidinedione derivative/ (10823)
226 (thiazolidinedione* or TZD or TZDs).tw,kw. (12397)
227 pioglitazone/ (14830)
228 (pioglitazone* or actos or AD 4833 or piomed or U 72107A or U72 107A or cereluc or glidipion or glita or glitase or glustin or paglitaz or pioglit or sepioglin or zactos).tw,kw. (11333)
229 112529-15-4.rn. (0)
230 rosiglitazone/ (15989)
231 (rosiglitazone* or avandia or BRL 49653-C or BRL 49653 or nyracta or rezult or rossini or venvia).tw,kw. (12978)
232 155141-29-0.rn. (14702)
233 glucagon like peptide 1 receptor agonist/ (2110)
234 ((glucagon-like peptide-1 or GLP-1 or GLP1 or GLP-1R or GLP1R) adj2 analog*).tw,kw. (2996)
235 ((glucagon-like peptide-1 or GLP-1 or GLP1 or GLP-1R or GLP1R) adj2 (receptor? or protein?)).tw,kw. (7207)
236 ((glucagon-like peptide-1 or GLP-1 or GLP1 or GLP-1R or GLP1R) adj2 agonist*).tw,kw. (5289)
237 incretin mimetic*.tw,kw. (754)
238 dulaglutide/ (307)
239 (dulaglutide or LY-2189265 or LY2189265 or trulicity).tw,kw. (315)
240 923950-08-7.rn. (211)
241 exendin 4/ (7217)
242 (AC 2993 or AC 2993A or AC-2993 or AC002993 or AC2993 or AC2993A or baietta or byetta or bydureon or DA 3091 or exenatide or exendin 4 or HSDB 7789 or LY 2148568 or LY2148568 or PT302 or Ex4 peptide or ITCA 650).tw,kw. (7065)
243 141758-74-9.rn. (5627)
244 liraglutide/ (4905)
245 (liraglutida or liraglutide or liraglutidum or HSDB 8205 or NN-2211 or NN2211 or NNC 90-1170 or saxenda or victoza).tw,kw. (3920)
246 204656-20-2.rn. (3097)
247 long acting insulin/ (4078)
248 ((long-acting or LA or semilente or semi-lente or slow* acting or intermediate-acting) adj (insulin* or analog*)).tw,kw. (3627)
249 insulin detemir/ (3156)
250 (detemir or determir or levemir or NN-304 or NN304).tw,kw. (2636)
251 169148-63-4.rn. (2341)
252 insulin glargine/ (8182)
253 (abasaglar or abasria or basaglar or glargine or HOE-901 or HOE901 or lantus or ly 2963016 or ly2963016 or optisulin or toujeo).tw,kw. (6280)
254 160337-95-1.rn. (5715)
255 short acting insulin/ (820)
256 ((fast-acting or quick-acting or short-acting or rapid* acting) adj (insulin? or analog*)).tw,kw. (3052)
257 insulin aspart/ (4398)
258 (insulin aspart* or (B28 adj1 insulin?) or (B28 adj1 insulin?) or (B28asp* adj1 insulin?) or NovoLog* or NovoMix* or Novo Mix* or NovoRapid*).tw,kw. (3086)
259 116094-23-6.rn. (3429)
260 insulin lispro/ (5176)
261 (lispro or lyspro or humalog or liprolog or ly 275585 or ly275585).tw,kw. (3714)
262 133107-64-9.rn. (4016)
263 isophane insulin/ (7863)
264 (actraphan? or berlinsulin or "humulin i" or "humulin n" or insulatard or (insulin? adj3 monotard) or isophane or (insulin? adj2 NPH) or (insulin? adj2 protamine) or isofane or isophan or isophane or isophone or mixtard or novolin or nph iletin or nph umuline or orgasuline or protaphan or protaphane or protophane or prozinc or (zinc adj2 insulin?) or (zinc adj1 protamine)).tw,kw. (6799)
265 9004-17-5.rn. (6246)
266 (insulin? adj1 regular).tw,kw. (2886)
267 human insulin/ (4542)
268 (insulin? adj1 human).tw,kw. (12859)
269 (h tronin or humulin or nazlin).tw,kw. (1813)
270 pig insulin/ (1396)
271 ((insulin? adj1 (pork or porcine or pig or pigs)) or hypurin).tw,kw. (2880)
272 alogliptin plus metformin/ (25)
273 (alogliptin adj3 metformin).tw,kw. (27)
274 (metformin adj2 nesina).tw,kw. (0)
275 (kazano or nesimet or nesina or nesinamet or vipdomet).tw,kw. (80)
276 linagliptin plus metformin/ (41)
277 (linagliptin adj2 metformin).tw,kw. (72)
278 (jentadueto or trajenta duo or trajentamet or trayebta duo or trayenta duo).tw,kw. (28)
279 metformin plus saxagliptin/ (71)
280 (saxagliptin adj3 metformin).tw,kw. (135)
281 (komboglyze or kombiglyze or comboglyze or duoglyze).tw,kw. (35)
282 metformin plus sitagliptin/ (271)
283 (sitagliptin adj3 metformin).tw,kw. (459)
284 (janumet or efficib or gliptamet or Januet or ristfor or velmetia or mk 0431a).tw,kw. (169)
285 dapagliflozin plus metformin/ (19)
286 (metformin adj3 dapagliflozin).tw,kw. (70)
287 (ebymect or Xigduo).tw,kw. (20)
288 empagliflozin plus metformin/ (3)
289 (empagliflozin adj3 metformin).tw,kw. (22)
290 (jardiamet or jardiancemet or synjardy).tw,kw. (3)
291 metformin plus rosiglitazone/ (427)
292 (metformin adj3 rosiglitazone).tw,kw. (817)
293 (avandamet or interac).tw,kw. (308)
294 622402-70-4.rn. (0)
295 glycosidase inhibitor/ (1164)
296 ((alpha-amylase or alpha-glucosidase or glucosidase or glycoside) adj2 inhibitor?).tw,kw. (6829)
297 acarbose/ (7337)
298 (acarbose or ag 5421 or ag5421 or alpha ghi or bay g 5421 or bay g5421 or glibose or glicobase or glucobay or gluconase or glucor or glumida or prandase or precise or rebose).tw,kw. (307456)
299 56180-94-0.rn. (5929)
300 meglitinide/ (1388)
301 (hb 699 or hb699 or meglitinide?).tw,kw. (642)
302 repaglinide/ (3158)
303 (actulin or ag ee 388 or ag ee388 or ag ee 623 or ag ee623 or enyglid or gluconorm or novonorm or prandin or rapilan or repaglinide or sestrine).tw,kw. (1882)
304 135062-02-1.rn. (3031)
305 nateglinide/ (2352)
306 (a 4166 or a4166 or ay 4166 or ay4166 or djn 608 or djn608 or fasticor or glinate or nateglinide or sdz djn 608 or sdz djn608 or senaglinide or starlix or starsis or trazec or "ym 026").tw,kw. (1413)
307 105816-04-4.rn. (2291)
308 miglitol/ (1309)
309 (bay 1099 or bay m 1099 or bay m1099 or bay1099 or diastabol or glyset or miglitol or plumarol).tw,kw. (855)
310 72432-03-2.rn. (1271)
311 voglibose/ (928)
312 (ao 128 or ao128 or basen or "en 116 077" or en 116077 or "en116 077" or en116077 or glustat or voglibose).tw,kw. (713)
313 83480-29-9.rn. (1011)
314 or/162-313 (587197)
315 159 and 314 (138063)
316 randomized controlled trial/ or controlled clinical trial/ (1029931)
317 exp "clinical trial (topic)"/ (183028)
318 (randomi#ed or randomly or RCT$1 or placebo*).tw. (1662366)
319 ((singl* or doubl* or trebl* or tripl*) adj (mask* or blind* or dumm*)).tw. (328932)
320 trial.ti. (349371)
321 or/316-320 (2287790)
322 315 and 321 (24744)
323 exp animal experimentation/ or exp models animal/ or exp animal experiment/ or nonhuman/ or exp vertebrate/ (42125725)
324 exp human/ or exp human experimentation/ or exp human experiment/ (32720153)
325 323 not 324 (9407230)
326 322 not 325 (23943)
327 exp Juvenile/ not (exp Adult/ and exp Juvenile/) (2103525)
328 326 not 327 (23758)
329 editorial.pt. (896572)
330 letter.pt. not (letter.pt. and randomized controlled trial/) (1822001)
331 328 not (329 or 330) (23398)
332 331 use emczd (16259)
333 153 or 332 (25837)
334 limit 333 to yr="2014-2016" (5544)
335 remove duplicates from 334 (4459)
336 limit 333 to yr="2012-2013" (4826)
337 remove duplicates from 336 (3926)
338 limit 333 to yr="2009-2011" (5440)
339 remove duplicates from 338 (4300)
340 limit 333 to yr="2002-2008" (5814)
341 remove duplicates from 340 (4233)
342 limit 333 to yr="1800-2001" (4211)
343 remove duplicates from 342 (3246)
344 335 or 337 or 339 or 341 or 343 (20164) [TOTAL UNIQUE RECORDS]
345 344 use prmz (9490) [MEDLINE UNIQUE RECORDS]
346 344 use emczd (10674) [EMBASE UNIQUE RECORDS]

***************************

Cochrane Library

Search Name: Type 2 Diabetes - Hypoglycemic Agents
Date Run:        05/03/16 13:35:59.364
Description:     2016 Mar 5 - Ottawa Heart Institute - Final

ID Search Hits
#1 [mh "Diabetes Mellitus, Type 2"]      10494
#2 [mh ^"Diabetes Mellitus"]      2731
#3 ((adult or "ketosis-resistant" or matur* or late or ("non-insulin" next depend*) or (noninsulin next depend*) or slow or stable or "type 2" or "type II" or lipoatrophic) near/3 diabet*):ti,ab,kw      19979
#4 (MODY or NIDDM or T2DM):ti,ab,kw      2925
#5 [or #1-#4]      22212
#6 [mh "Diabetes Mellitus, Type 2"/DT]      4793
#7 [mh "Drug Combinations"]      11668
#8 [mh ^"Drug Therapy, Combination"]      27341
#9 #6 and (#7 or #8)      1080
#10  [mh "Hypoglycemic Agents"]      6208
#11 (antidiabetic* or (anti next diabetic*) or antihyperglycemic* or antihyperglycaemic* or (anti next hyperglycemic*) or (anti next hyperglycaemic*) or hypoglycemic* or hypoglycaemic* or antidiabetes or (anti next diabetes)):ti,ab,kw      8917
#12 [mh "Dipeptidyl-Peptidase IV Inhibitors"]      387
#13 ((DPP4 or "DPP 4" or "DPP IV") near/1 inhibitor*):ti,ab,kw      379
#14 ("dipeptidyl-peptidase IV" near/2 inhibitor*):ti,ab,kw      592
#15 ("dipeptidyl-peptidase 4" near/2 inhibitor*):ti,ab,kw      281
#16 (gliptin or gliptins):ti,ab,kw      9
#17 (alogliptin or nesina or "SYR 322" or SYR322 or "HSDB 8203" or incresina or vipidia):ti,ab,kw      87
#18 [mh Linagliptin]      52
#19 (linagliptin or "BI 1356" or ONDERO or tradjenta or trajenta or trayenta or trazenta):ti,ab,kw      154
#20  (saxagliptin or "BMS 477118" or BMS477118 or "HSDB 8199" or Onglyza or "OPC 262"):ti,ab,kw      163
#21 [mh "Sitagliptin Phosphate"]      206
#22 (sitagliptin or "EC 690-730-1" or Glactiv or "HSDB 7516" or januvia or "mk 0431" or mk0431 or "mk 431" or "ono 5435" or ristaben or sitagliptine or tesabel or tesavel or xelevia):ti,ab,kw      533
#23 [mh "Sodium-Glucose Transporter 2"/AI]      85
#24 (("sodium-glucose transporter 2" or "sodium-glucose cotransporter 2") next inhibitor*):ti,ab,kw      95
#25 (("sodium-glucose transporter 2" or "sodium-glucose co-transporter 2") next inhibitor*):ti,ab,kw      66
#26  (("SGLT-2" or SGLT2) next inhibitor*):ti,ab,kw      171
#27  (("sodium dependent glucose transporter 2" or "sodium dependent glucose cotransporter 2") next inhibitor*):ti,ab,kw      2
#28 (("sodium dependent glucose transporter 2" or "sodium dependent glucose co-transporter 2") next inhibitor*):ti,ab,kw      1
#29 (gliflozin or gliflozins):ti,ab,kw      1
#30 [mh Canagliflozin]      44
#31 (canagliflozin or Invokana or (JNJ next 24831754*) or "JNJ 28431754" or "TA 7284" or Prominad):ti,ab,kw      115
#32  (dapagliflozin or "BMS 512148" or BMS512148 or edistride or forxiga or farxiga):ti,ab,kw      173
#33 (empagliflozin or "BI 10773" or BI10773 or Jardiance):ti,ab,kw      138
#34 [mh ^"Sulfonylurea Compounds"]      649
#35 (sulfonylurea* or sulfonurea* or (sulfonyl next urea*) or sulfonylcarbamide* or sulphonurea* or sulphonylurea*):ti,ab,kw      1858
#36  [mh Chlorpropamide]      74
#37  (adiaben or "apo-chlorpropamide" or apochlorpropamide or abemide or "arodoc c" or asucrol or ascurol or biabenal or bioglumin or "BRN 2218363" or catanil or "CCRIS 155" or chlomide or chlormide or chlorodiabina or chloropropamide or chlorpromide or clorpropamide or copamide or chloronase or chlorpromide or clorpropamide or chloropropamide or chlorpropamid or chlorpropamide or chlorpropamidum or clorpropamid or clorpropamida):ti,ab,kw      126
#38 (dabinese or deavynfar or diabaril or diabechlor or diabeedol or diabemide or diabenal or diabenese or diabeneza or "diabet-pages" or diabetoral or diabexan or diabiclor or diabines or diabinese or diabitex or diabitol or "diamel ex" or dibecon or dynalase or "EINECS 202-314-5" or eubetin or glicoben or glisema or glucamide or glycemin or glymese or "HSDB 2051" or hypomide or insilange or insogen or insulase):ti,ab,kw      3
#39 (melormin or meldian or melitase or mellinese or millinese or "NCI-C01752" or "NSC 44634" or "NSC 626720" or "neo-toltinon" or oradian or "P 607" or pamidin or prodiaben or pubetin or stabinol or tesmel or "p chlorobenzolsulphonylglycolic acid nitrile" or "para chlorobenzenesulfonylglycolic acid nitrile" or "parachlorobenzene sulfonylglycolic acid nitrile" or "U-3818" or "U-9818"):ti,ab,kw      7
#40 [mh Gliclazide]      154
#41 (gliclazide or diaglyk or diaikron or diabrezide or diamicron or "BRN 1657836" or "EINECS 244-260-5" or "gen-gliclazide" or gliklazid or gliclazida or gliclazidum or glimicron or glyade or glyclazide or glycazide or nordialex or predian or "S 1702" or "S 852" or "SE 1702"):ti,ab,kw      368
#42  (glimepiride or amaryl or amarel or "BRN 5365754" or "CCRIS 7083" or endial or euglim or glemax or glimepirid or glimepirida or glimepiridum or glimerid or glorion or "HOE 490" or HOE490 or solosa or "s 80 8490"):ti,ab,kw      537
#43 [mh Glyburide]      506
#44 (adiab or amecladin or "apo-glibenclamide" or azuglucon or bastiverit or benclamin or betanase or "betanese 5" or "BRN 2230085" or calabren or clamide or clibenclamide or cytagon or dangbinol or daonil or debtan or diabasan or diabeta or dibelet or duraglucon or "EINECS 233-570-6" or euclamin or euglucan or euglucon or euglykon):ti,ab,kw      33
#45 ("GBN 5" or "gen-glybe" or gewaglucon or gilemal or glamide or glencamide or gliban or glibeclamid or glibemid or gliben or glibenbeta or glibenclamid or glibenclamida or glibenclamide or glibenclamidum or glibenhexal or glibenil or glibens or glibesyn or glibet or glibetic or glibil or gliboral or glicem or glidiabet or gliformin or glikeyer or glimel or glimide or glimidstada or glisulin or glitisol or glubate or gluben):ti,ab,kw      763
#46 (glucobene or glucohexal or glucolon or glucomid or gluconic or glucoremed or glucoven or glukoreduct or glulo or glyamid or glyben or glybencamidum or glybencenamide or glybenclamid or glybenclamide or glybendamine or glybenzyclamide or glybenzcyclamide or glyburide or glycolande or glycomin or glynase or "HB 419" or "HB 420" or "hemi-daonil" or hexaglucon or humedia or insol or lederglib or libanil or lisaglucon or locose or lodulce):ti,ab,kw      632
#47 (maninil or manoglucon or "med-glionil" or melix or micronase or miglucan or nadib or neogluconin or "norglicem 5" or normoglucon or orabetic or pira or praeciglucon or prodiabet or renabetic or "RP-1127" or "semi-daonil" or "semi-euglucon" or "semi-gliben-puren n" or sugril or suraben or tiabet or "U 26452" or "U-26 452" or "UR 606" or yuglucon or xeltic):ti,ab,kw      14
#48 [mh Tolbutamide]      135
#49 (abemin or aglicem or aglicid or aglycid or "apo-tolbutamide" or arcosal or arkozal or artosin or artosina or artozin or beglucin or "BRN 1984428" or butamid or butamide or butamidum or "CCRIS 592" or "D 860" or diabecid or diaben or diabenyl or diabeton or diabesan or diasulfon or diabetamid or diabetol or diabuton or diatol or dirastan or diasulin or diaval or dolipol or drabet):ti,ab,kw      0
#50 ("EINECS 200-594-3" or fresan or glicemin or glicotron or glycotron or guabeta or glyconon or "HLS 831" or "HSDB 3393" or hypoglycone or ipoglicone or ipoglucos or mermol or "metil glucosulfina" or mobenol or "NCI-C01763" or "NSC 23813" or "neo antiglycemikos" or "neo diabetal" or "neo norboral" or neobellin or neoinsoral):ti,ab,kw      0
#51 (orabet or oralin or oresan or orezan or orinade or orinase or orinaz or orsinon or osdiabet or oterben or pramidex or proinsul or rastinon or "SK-tolbutamide" or tarasina or tobutamine or tol ortab or tolbet or tolbugen or tolbusal or tolbutamid or tolbutamida or tolbutamide or tolbutamidum or tolbutone or tolbutamte or tolbutol or tolbutylharnstoff or tolbutylurea or tolglybutamide or tolsiran or tolubetin or toluran or tolurast or tosula or toluina or tolumid or toluvan or tolylsulfonylbutylurea or "U 2043" or willbutamide):ti,ab,kw      230
#52 [mh Thiazolidinediones]      1248
#53 (thiazolidinedione* or TZD or TZDs):ti,ab,kw      1554
#54 (pioglitazone* or actos or "AD 4833" or piomed or "U 72107A" or "U72 107A" or cereluc or glidipion or glita or glitase or glustin or paglitaz or pioglit or sepioglin or zactos):ti,ab,kw      1224
#55 (rosiglitazone* or avandia or "BRL 49653-C" or "BRL 49653" or nyracta or rezult or rossini or venvia):ti,ab,kw      817
#56 [mh "Glucagon-Like Peptide 1"/AA]      147
#57 (("glucagon-like peptide-1" or "GLP-1" or GLP1 or "GLP-1R" or GLP1R) near/2 analog*):ti,ab,kw      170
#58  [mh "Glucagon-Like Peptide-1 Receptor"]      48
#59 (("glucagon-like peptide-1" or "GLP-1" or GLP1 or "GLP-1R" or GLP1R) near/2 (receptor* or protein*)):ti,ab,kw      344
#60  [mh "Receptors, Glucagon"/AG]      47
#61 (("glucagon-like peptide-1" or "GLP-1" or GLP1 or "GLP-1R" or GLP1R) near/2 agonist*):ti,ab,kw      309
#62 (incretin next mimetic*):ti,ab,kw      23
#63 (dulaglutide or "LY-2189265" or LY2189265 or trulicity):ti,ab,kw      62
#64 ("AC 2993" or "AC 2993A" or "AC-2993" or AC002993 or AC2993 or AC2993A or baietta or byetta or bydureon or "DA 3091" or exenatide or "exendin 4" or "HSDB 7789" or "LY 2148568" or "LY2148568" or PT302 or "Ex4 peptide" or "ITCA 650"):ti,ab,kw      421
#65 [mh Liraglutide]      106
#66 (liraglutida or liraglutide or liraglutidum or "HSDB 8205" or "NN-2211" or NN2211 or "NNC 90-1170" or saxenda or victoza):ti,ab,kw      378
#67 [mh "Insulin, Long-Acting"]      776
#68 (("long-acting" or LA or semilente or semi-lente or (slow* next acting) or "intermediate-acting") next (insulin* or analog*)):ti,ab,kw      290
#69 [mh "Insulin Detemir"]      103
#70 (detemir or determir or levemir or "NN-304" or NN304):ti,ab,kw      297
#71 [mh "Insulin Glargine"]      368
#72 (abasaglar or abasria or basaglar or glargine or "HOE-901" or HOE901 or lantus or "ly 2963016" or ly2963016 or optisulin or toujeo):ti,ab,kw      935
#73 [mh "Insulin, Short-Acting"]      488
#74 (("fast-acting" or "quick-acting" or "short-acting" or (rapid* next acting)) next (insulin* or analog*)):ti,ab,kw      374
#75 ((insulin next aspart*) or (B28 near/1 insulin*) or (B28 near/1 insulin*) or (B28asp* near/1 insulin*) or NovoLog* or NovoMix* or (Novo next Mix*) or NovoRapid*):ti,ab,kw      534
#77  (apidra or glulisine):ti,ab,kw      125
#78 [mh "Insulin, Isophane"]      304
#79 (actraphan* or berlinsulin or "humulin i" or "humulin n" or insulatard or (insulin* near/3 monotard) or isophane or (insulin* near/2 NPH) or (insulin* near/2 protamine) or isofane or isophan or isophane or isophone or mixtard or novolin or "nph iletin" or "nph umuline" or orgasuline or protaphan or protaphane or protophane or prozinc or (zinc near/2 insulin*) or (zinc near/1 protamine)):ti,ab,kw      829
#80 [mh Insulin]      9438
#81 (insulin* near/1 regular):ti,ab,kw      403
#82 (insulin* near/1 human):ti,ab,kw      2565
#83 ((nph next insulin*) or humulin or novolin):ti,ab,kw      428
#84 ((insulin* near/1 (pork or porcine or pig or pigs)) or hypurin):ti,ab,kw      167
#85 (alogliptin near/3 metformin):ti,ab,kw      8
#86  (metformin near/2 nesina):ti,ab,kw      0
#87 (kazano or nesimet or nesina or nesinamet or vipdomet):ti,ab,kw      1
#88 (linagliptin near/2 metformin):ti,ab,kw      42
#89 (jentadueto or "trajenta duo" trajentamet or "trayebta duo" or "trayenta duo"):ti,ab,kw      2
#90 (saxagliptin near/3 metformin):ti,ab,kw      52
#91 (komboglyze or kombiglyze or comboglyze or duoglyze):ti,ab,kw      2
#92 [mh "Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination"]      1
#93 (sitagliptin near/3 metformin):ti,ab,kw      119
#94 (janumet or efficib or gliptamet or Januet or ristfor or velmetia or "mk 0431a"):ti,ab,kw      2
#95  (metformin near/3 dapagliflozin):ti,ab,kw      43
#96 (ebymect or xigduo):ti,ab,kw      0
#97 (empagliflozin near/3 metformin):ti,ab,kw      25
#98 (jardiamet or jardiancemet or synjardy):ti,ab,kw      0
#99 (metformin near/3 rosiglitazone):ti,ab,kw      185
#100 (avandamet or interac):ti,ab,kw      8
#101 [mh "Glycoside Hydrolase Inhibitors"]      137
#102 (("alpha-amylase" or "alpha-glucosidase" or glucosidase or glycoside) near/2 inhibitor*)      438
#103 [mh Acarbose]      238
#104 (acarbose or "ag 5421" or ag5421 or "alpha ghi" or "bay g 5421" or "bay g5421" or glibose or glicobase or glucobay or gluconase or glucor or glumida or prandase or precise or rebose):ti,ab,kw      2642
#105 ("hb 699" or hb699 or meglitinide*):ti,ab,kw      38
#106 (actulin or "ag ee 388" or "ag ee388" or "ag ee 623" or "ag ee623" or enyglid or gluconorm or novonorm or prandin or rapilan or repaglinide or sestrine):ti,ab,kw       207
#107  ("a 4166" or a4166 or "ay 4166" or ay4166 or "djn 608" or djn608 or fasticor or glinate or nateglinide or "sdz djn 608" or "sdz djn608" or senaglinide or starlix or starsis or trazec or "ym 026"):ti,ab,kw      172
#108 ("bay 1099" or "bay m 1099" or "bay m1099" or bay1099 or diastabol or glyset or miglitol or plumarol):ti,ab,kw      127
#109 ("ao 128" or ao128 or basen or "en 116 077" or "en 116077" or "en116 077" or en116077 or glustat or voglibose):ti,ab,kw      120
#110 [or #9-#109]      22251
#111 #5 and #110      10283

 

CENTRAL – 9573

PubMed
2016 Mar 17
Most recent and publisher-supplied records only

Search Query Items found
#90 Search #88 AND #89 53
#89 Search publisher[sb] OR 2016/03/01:2016/03/17 487139
#88 Search #85 NOT (#86 OR #87) 11953
#87 Search letter[pt] NOT (letter[pt] AND randomized controlled trial[pt]) 903578
#86 Search comment[pt] OR editorial[pt] OR interview[pt] OR news[pt] OR newspaper article[pt] 1128869
#85 Search #80 NOT #84 12435
#84 Search #81 OR #82 OR #83 1621786
#83 Search Infant[mesh] not (Adult[mesh] and Infant[mesh]) 735164
#82 Search Child[mesh] not (Adult[mesh] and Child[mesh]) 1037160
#81 Search Adolescent[mesh] not (Adult[mesh] and Adolescent[mesh]) 508484
#80 Search #78 NOT #79 12561
#79 Search Animals[mesh] NOT (Animals[mesh] AND humans[mesh]) 4187523
#78 Search (#76 AND #77) 12808
#77 Search (#4 AND #69) 75398
#76 Search #71 or #72 or #73 OR #74 OR #75 1115734
#75 Search trial [ti] 149291
#74 Search single blind*[tw] OR single mask*[tw] OR single dumm*[tw] OR double blind*[tw] OR double mask*[tw] OR double dumm*[tw] OR triple blind*[tw] OR triple mask*[tw] OR triple dumm*[tw] OR treble blind*[tw] OR treble mask*[tw] OR treble dumm*[tw] 193913
#73 Search randomised[tw] OR randomized[tw] OR randomly[tw] or RCT[tw] OR RCTs[tw] OR placebo*[tw] 870866
#72 Search "clinical trials as topic"[mesh] 287364
#71 Search controlled clinical trial[pt] OR randomized controlled trial[pt] 492381
#69 Search #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 2755452
#68 Search "ao 128"[tw] OR ao128[tw] OR basen[tw] OR "en 116 077"[tw] OR "en 116077"[tw] OR "en116 077"[tw] OR en116077[tw] OR glustat[tw] OR voglibose[tw] 274
#67 Search "hb 699"[tw] OR hb699[tw] OR meglitinide*[tw] OR actulin[tw] OR "ag ee 388"[tw] OR "ag ee388"[tw] OR "ag ee 623"[tw] OR "ag ee623"[tw] OR enyglid[tw] OR gluconorm[tw] OR novonorm[tw] OR prandin[tw] OR rapilan[tw] OR repaglinide[tw] OR sestrine[tw] OR "a 4166"[tw] OR a4166[tw] OR "ay 4166"[tw] OR ay4166[tw] OR "djn 608"[tw] OR djn608[tw] OR fasticor[tw] OR glinate[tw] OR nateglinide[tw] OR sdz djn 608[tw] OR sdz djn608[tw] OR senaglinide[tw] OR starlix[tw] OR starsis[tw] OR trazec[tw] OR "ym 026"[tw] OR "bay 1099"[tw] OR "bay m 1099"[tw] OR "bay m1099"[tw] OR bay1099[tw] OR diastabol[tw] OR glyset[tw] OR miglitol[tw] OR plumarol[tw] OR 0V5436JAQW[EC/RN Number] 1507
#66 Search acarbose[tw] OR "ag 5421"[tw] OR ag5421[tw] OR "alpha ghi"[tw] OR "bay g 5421"[tw] OR "bay g5421"[tw] OR glibose[tw] OR glicobase[tw] OR glucobay[tw] OR gluconase[tw] OR glucor[tw] OR glumida[tw] OR prandase[tw] OR precise[tw] OR rebose[tw] OR T58MSI464G[EC/RN Number] 135060
#65 Search Acarbose[mesh] 1140
#64 Search alpha-amylase inhibitor*[tw] OR alpha-glucosidase inhibitor*[tw] OR glucosidase inhibitor*[tw] OR glycoside inhibitor*[tw] 2631
#63 Search Glycoside Hydrolase Inhibitors[mesh] 1776
#62 Search (sitagliptin[tw] AND metformin[tw]) OR janumet[tw] OR efficib[tw] OR gliptamet[tw] OR Januet[tw] OR ristfor[tw] OR velmetia[tw] OR "mk 0431a"[tw] OR (metformin[tw] AND dapagliflozin[tw]) OR ebymect[tw] OR xigduo[tw] OR (empagliflozin[tw] AND metformin[tw]) OR jardiamet[tw] OR jardiancemet[tw] OR synjardy[tw] OR (metformin[tw] AND rosiglitazone[tw]) OR avandamet[tw] OR interac[tw] 1283
#61 Search "Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination"[mesh] 5
#60 Search (alogliptin[tw] AND metformin[tw]) OR (nesina[tw] AND metformin[tw]) OR kazano[tw] OR nesimet[tw] OR nesina[tw] OR nesinamet[tw] OR vipdomet[tw] OR (linagliptin[tw] AND metformin[tw]) OR jentadueto[tw] OR trajenta duo[tw] OR trajentamet[tw] OR trayebta duo[tw] OR trayenta duo[tw] OR (saxagliptin[tw] AND metformin[tw]) OR komboglyze[tw] OR kombiglyze[tw] OR comboglyze[tw] OR duoglyze[tw] 1313
#59 Search pork insulin*[tw] OR porcine insulin*[tw] OR pig insulin*[tw] OR pigs insulin*[tw] OR hypurin[tw] 7723
#58 Search regular insulin*[tw] OR human insulin*[tw] OR nph insulin*[tw] OR humulin[tw] OR novolin[tw] 7626
#57 Search Insulin [mesh] 165022
#56 Search actraphan*[tw] OR berlinsulin[tw] OR "humulin i"[tw] OR "humulin n"[tw] OR insulatard[tw] OR (insulin*[tw] AND monotard[tw]) OR isophane[tw] OR (insulin*[tw] AND NPH[tw]) OR (insulin*[tw] AND protamine[tw]) OR isofane[tw] OR isophan[tw] OR isophane[tw] OR isophone[tw] OR mixtard[tw] OR novolin[tw] OR “nph iletin”[tw] OR nph umuline[tw] OR orgasuline[tw] OR protaphan[tw] OR protaphane[tw] OR protophane[tw] OR prozinc[tw] OR zinc insulin*[tw] OR zinc protamine[tw] OR protamine zinc[tw] OR 2ZM8CX04RZ[EC/RN Number] 3436
#55 Search Insulin, Isophane[mesh] 917
#54 Search lispro[tw] OR lyspro[tw] OR humalog[tw] OR liprolog[tw] OR apidra[tw] OR glulisine[tw] OR 7XIY785AZD[EC/RN Number] 1309
#53 Search fast-acting insulin*[tw] OR quick-acting insulin*[tw] OR short-acting insulin*[tw] OR rapid acting insulin*[tw] OR rapidly acting insulin*[tw] OR fast-acting analog*[tw] OR quick-acting analog*[tw] OR short-acting analog*[tw] OR rapid acting analog*[tw] OR rapidly acting analog*[tw] OR insulin aspart*[tw] OR B28 insulin*[tw] OR B28 insulin*[tw] OR B28asp insulin*[tw] OR NovoLog*[tw] OR NovoMix*[tw] OR Novo Mix*[tw] OR NovoRapid*[tw] OR D933668QVX[EC/RN Number] 3630
#52 Search Insulin, Short-Acting[mesh] 1250
#51 Search abasaglar[tw] OR abasria[tw] OR basaglar[tw] OR glargine[tw] OR "HOE-901"[tw] OR HOE901[tw] OR lantus[tw] OR ly 2963016[tw] OR ly2963016[tw] OR optisulin[tw] OR toujeo[tw] OR 2ZM8CX04RZ[EC/RN Number] 2026
#50 Search Insulin Glargine[mesh] 1261
#49 Search detemir[tw] OR determir[tw] OR levemir[tw] OR "NN-304"[tw] OR NN304[tw] OR 4FT78T86XV[EC/RN Number] 820
#48 Search Insulin Detemir[mesh] 433
#47 Search long-acting insulin*[tw] OR LA insulin*[tw] OR semilente insulin*[tw] OR semi-lente insulin*[tw] OR slow acting insulin*[tw] OR slower acting insulin*[tw] OR intermediate-acting insulin*[tw] OR long-acting analog*[tw] OR LA analog*[tw] OR semilente analog*[tw] OR semi-lente analog*[tw] OR slow acting analog*[tw] OR slower acting analog*[tw] OR intermediate-acting analogn*[tw] 10580
#46 Search Insulin, Long-Acting[mh:noexp] 2528
#45 Search liraglutida[tw] OR liraglutide[tw] OR liraglutidum[tw] OR "HSDB 8205"[tw] OR "NN-2211"[tw] OR NN2211[tw] OR "NNC 90-1170"[tw] OR saxenda[tw] OR victoza[tw] OR 839I73S42A[EC/RN Number] 1286
#44 Search Liraglutide[mesh] 705
#43 Search "AC 2993"[tw] OR "AC 2993A"[tw] OR "AC-2993"[tw] OR AC002993[tw] OR AC2993[tw] OR AC2993A[tw] OR baietta[tw] OR byetta[tw] OR bydureon[tw] OR "DA 3091"[tw] OR exenatide[tw] OR "exendin 4"[tw] OR "HSDB 7789"[tw] OR LY 2148568[tw] OR LY2148568[tw] OR PT302[tw] OR "Ex4 peptide"[tw] OR "ITCA 650"[tw] OR 9P1872D4OL[EC/RN Number] 2536
#42 Search glucagon-like peptide-1 agonist*[tw] OR GLP-1 agonist*[tw] OR GLP1 agonist*[tw] OR GLP-1R agonist*[tw] OR GLP1R agonist*[tw] OR incretin mimetic*[tw] OR dulaglutide[tw] OR LY-2189265[tw] OR LY2189265[tw] OR trulicity[tw] OR WTT295HSY5[EC/RN Number] 1012
#41 Search "receptors, glucagon/agonists"[MeSH Terms] 710
#40 Search glucagon-like peptide-1 receptor*[tw] OR GLP-1 receptor*[tw] OR GLP1 receptor*[tw] OR GLP-1R receptor*[tw] OR GLP1R receptor*[tw] OR glucagon-like peptide-1 protein*[tw] OR GLP- protein*[tw] OR GLP1 protein*[tw] OR GLP-1R protein*[tw] OR GLP1R protein*[tw] 5630
#39 Search Glucagon-Like Peptide-1 Receptor[mesh] 1542
#38 Search glucagon-like peptide-1 analog*[tw] OR GLP-1 analog*[tw] OR GLP1 analog*[tw] OR GLP-1R analog*[tw] OR GLP1R analog*[tw] 1261
#37 Search "glucagon like peptide 1/analogs and derivatives"[MeSH] 977
#36 Search rosiglitazone*[tw] OR avandia[tw] OR "BRL 49653-C"[tw] OR "BRL 49653"[tw] OR nyracta[tw] OR rezult[tw] OR rossini[tw] OR venvia[tw] OR 05V02F2KDG[EC/RN Number] 5549
#35 Search thiazolidinedione*[tw] OR TZD[tw] OR TZDs[tw] OR pioglitazone*[tw] OR actos[tw] OR "AD 4833"[tw] OR piomed[tw] OR "U 72107A"[tw] OR "U72 107A"[tw] OR cereluc[tw] OR glidipion[tw] OR glita[tw] OR glitase[tw] OR glustin[tw] OR paglitaz[tw] OR pioglit[tw] OR sepioglin[tw] OR zactos[tw] OR X4OV71U42S[EC/RN Number] 12847
#34 Search Thiazolidinediones[mesh] 9929
#33 Search abemin[tw] OR aglicem[tw] OR aglicid[tw] OR aglycid[tw] OR apo-tolbutamide[tw] OR arcosal[tw] OR arkozal[tw] OR artosin[tw] OR artosina[tw] OR artozin[tw] OR beglucin[tw] OR "BRN 1984428"[tw] OR butamid[tw] OR butamide[tw] OR butamidum[tw] OR "CCRIS 592"[tw] OR "D 860"[tw] OR diabecid[tw] OR diaben[tw] OR diabenyl[tw] OR diabeton[tw] OR diabesan[tw] OR diasulfon[tw] OR diabetamid[tw] OR diabetol[tw] OR diabuton[tw] OR diatol[tw] OR dirastan[tw] OR diasulin[tw] OR diaval[tw] OR dolipol[tw] OR drabbet[tw] OR EINECS 200-594-3[tw] OR fresan[tw] OR glicemin[tw] OR glicotron[tw] OR glycotron[tw] OR guabeta[tw] OR glyconon[tw] OR "HLS 831"[tw] OR "HSDB 3393"[tw] OR hypoglycone[tw] OR ipoglicone[tw] OR ipoglucos[tw] OR mermol[tw] OR metil glucosulfina[tw] OR mobenol[tw] OR NCI-C01763[tw] OR NSC 23813[tw] OR neo antiglycemikos[tw] OR neo diabetal[tw] OR neo norboral[tw] OR neobellin[tw] OR neoinsoral[tw] OR orabet[tw] OR oralin[tw] OR oresan[tw] OR orezan[tw] OR orinade[tw] OR orinase[tw] OR orinaz[tw] OR orsinon[tw] OR osdiabet[tw] OR oterben[tw] OR pramidex[tw] OR proinsul[tw] OR rastinon[tw] OR SK-tolbutamide[tw] OR tarasina[tw] OR tobutamine[tw] OR tol ortab[tw] OR tolbet[tw] OR tolbugen[tw] OR tolbusal[tw] OR tolbutamid[tw] OR tolbutamida[tw] OR tolbutamide[tw] OR tolbutamidum[tw] OR tolbutone[tw] OR tolbutamte[tw] OR tolbutol[tw] OR tolbutylharnstoff[tw] OR tolbutylurea[tw] OR tolglybutamide[tw] OR tolsiran[tw] OR tolubetin[tw] OR toluran[tw] OR tolurast[tw] OR tosula[tw] OR toluina[tw] OR tolumid[tw] OR toluvan[tw] OR tolylsulfonylbutylurea[tw] OR "U 2043"[tw] OR willbutamide[tw] OR 982XCM1FOI[EC/RN Number] 6637
#32 Search Tolbutamide[mesh] 5173
#31 Search glucobene[tw] OR glucohexal[tw] OR glucolon[tw] OR glucomid[tw] OR gluconic[tw] OR glucoremed[tw] OR glucoven[tw] OR glukoreduct[tw] OR glulo[tw] OR glyamid[tw] OR glyben[tw] OR glybencamidum[tw] OR glybencenamide[tw] OR glybenclamid[tw] OR glybenclamide[tw] OR glybendamine[tw] OR glybenzyclamide[tw] OR glybenzcyclamide[tw] OR glyburide[tw] OR glycolande[tw] OR glycomin[tw] OR glynase[tw] OR "HB 419"[tw] OR "HB 420"[tw] OR hemi-daonil[tw] OR hexaglucon[tw] OR humedia[tw] OR insol[tw] OR lederglib[tw] OR libanil[tw] OR lisaglucon[tw] OR locose[tw] OR lodulce[tw] OR maninil[tw] OR manoglucon[tw] OR med-glionil[tw] OR melix[tw] OR micronase[tw] OR miglucan[tw] OR nadib[tw] OR neogluconin[tw] OR "norglicem 5"[tw] OR normoglucon[tw] OR orabetic[tw] OR pira[tw] OR praeciglucon[tw] OR prodiabet[tw] OR renabetic[tw] OR "RP-1127"[tw] OR semi-daonil[tw] OR semi-euglucon[tw] OR semi-gliben-puren n[tw] OR sugril[tw] OR suraben[tw] OR tiabet[tw] OR "U 26452"[tw] OR "U-26 452"[tw] OR "UR 606"[tw] OR yuglucon[tw] OR xeltic[tw] OR SX6K58TVWC[EC/RN Number] 2434824
#30 Search adiab[tw] OR amecladin[tw] OR apo-glibenclamide[tw] OR azuglucon[tw] OR bastiverit[tw] OR benclamin[tw] OR betanase[tw] OR "betanese 5"[tw] OR "BRN 2230085"[tw] OR calabren[tw] OR clamide[tw] OR clibenclamide[tw] OR cytagon[tw] OR dangbinol[tw] OR daonil[tw] OR debtan[tw] OR diabasan[tw] OR diabeta[tw] OR dibelet[tw] OR duraglucon[tw] OR EINECS 233-570-6[tw] OR euclamin[tw] OR euglucan[tw] OR euglucon[tw] OR euglykon[tw] OR "GBN 5"[tw] OR gen-glybe[tw] OR gewaglucon[tw] OR gilemal[tw] OR glamide[tw] OR glencamide[tw] OR gliban[tw] OR glibeclamid[tw] OR glibemid[tw] OR gliben[tw] OR glibenbeta[tw] OR glibenclamid[tw] OR glibenclamida[tw] OR glibenclamide[tw] OR glibenclamidum[tw] OR glibenhexal[tw] OR glibenil[tw] OR glibens[tw] OR glibesyn[tw] OR glibet[tw] OR glibetic[tw] OR glibil[tw] OR gliboral[tw] OR glicem[tw] OR glidiabet[tw] OR gliformin[tw] OR glikeyer[tw] OR glimel[tw] OR glimide[tw] OR glimidstada[tw] OR glisulin[tw] OR glitisol[tw] OR glubate[tw] OR gluben[tw] 7433
#29 Search Glyburide[mesh] 5752
#28 Search glimepiride[tw] OR amaryl[tw] OR amarel[tw] OR "BRN 5365754" [tw] OR "CCRIS 7083" [tw] OR endial[tw] OR euglim[tw] OR glemax[tw] OR glimepirid[tw] OR glimepirida[tw] OR glimepiridum[tw] OR glimerid[tw] OR glorion[tw] OR "HOE 490" [tw] OR HOE490[tw] OR solosa[tw] OR "s 80 8490"[tw] OR 6KY687524K[EC/RN Number] 1092
#27 Search gliclazide[tw] OR diaglyk[tw] OR diaikron[tw] OR diabrezide[tw] OR diamicron[tw] OR "BRN 1657836"[tw] OR EINECS 244-260-5[tw] OR gen-gliclazide[tw] OR gliklazid[tw] OR gliclazida[tw] OR gliclazidum[tw] OR glimicron[tw] OR glyade[tw] OR glyclazide[tw] OR glycazide[tw] OR nordialex[tw] OR predian[tw] OR "S 1702"[tw] OR "S 852"[tw] OR "SE 1702"[tw] OR G4PX8C4HKV[EC/RN Number] 1210
#26 Search Gliclazide[mesh] 767
#25 Search melormin[tw] OR meldian[tw] OR melitase[tw] OR mellinese[tw] OR millinese[tw] OR NCI-C01752[tw] OR "NSC 44634"[tw] OR "NSC 626720"[tw] OR neo-toltinon[tw] OR oradian[tw] OR "P 607"[tw] OR pamidin[tw] OR prodiaben[tw] OR pubetin[tw] OR stabinol[tw] OR tesmel[tw] OR "p chlorobenzolsulphonylglycolic acid nitrile"[tw] OR para chlorobenzenesulfonylglycolic acid nitrile[tw] OR parachlorobenzene sulfonylglycolic acid nitrile[tw] OR "U-3818"[tw] OR "U-9818"[tw] OR WTM2C3IL2X[EC/RN Number] 1843
#24 Search adiaben[tw] OR apo-chlorpropamide[tw] OR apochlorpropamide[tw] OR abemide[tw] OR "arodoc c"[tw] OR asucrol[tw] OR ascurol[tw] OR biabenal[tw] OR bioglumin[tw] OR BRN 2218363[tw] OR catanil[tw] OR "CCRIS 155"[tw] OR chlomide[tw] OR chlormide[tw] OR chlorodiabina[tw] OR chloropropamide[tw] OR chlorpromide[tw] OR clorpropamide[tw] OR copamide[tw] OR chloronase[tw] OR chlorpromide[tw] OR clorpropamide[tw] OR chloropropamide[tw] ORchlorpropamid[tw] OR chlorpropamide[tw] OR chlorpropamidum[tw] OR clorpropamid[tw] OR clorpropamida[tw] OR dabinese[tw] OR deavynfar[tw] OR diabaril[tw] OR diabechlor[tw] OR diabeedol[tw] OR diabemide[tw] OR diabenal[tw] OR diabenese[tw] OR diabeneza[tw] OR diabet-pages[tw] OR diabetoral[tw] OR diabexan[tw] OR diabiclor[tw] OR diabines[tw] OR diabinese[tw] OR diabitex[tw] OR diabitol[tw] OR diamel ex[tw] OR dibecon[tw] OR dynalase[tw] OR EINECS 202-314-5[tw] OR eubetin[tw] OR glicoben[tw] OR glisema[tw] OR glucamide[tw] OR glycemin[tw] OR glymese[tw] OR HSDB 2051[tw] OR hypomide[tw] OR insilange[tw] OR insogen[tw] OR insulase[tw] 2067
#23 Search Chlorpropamide[mesh] 1809
#22 Search sulfonylurea*[tw] OR sulfonurea*[tw] OR sulfonyl urea*[tw] OR sulfonylcarbamide*[tw] OR sulphonurea*[tw] OR sulphonylurea*[tw] 11088
#21 Search Sulfonylurea Compounds[mh:noexp] 5254
#20 Search empagliflozin[tw] OR "BI 10773"[tw] OR BI10773[tw] OR Jardiance[tw] OR HDC1R2M35U[EC/RN Number] 236
#19 Search dapagliflozin[tw] OR "BMS 512148"[tw] OR BMS512148[tw] OR edistride[tw] OR forxiga[tw] OR farxiga[tw] OR 1ULL0QJ8UC[EC/RN Number] 320
#18 Search canagliflozin[tw] OR Invokana[tw] OR JNJ 24831754*[tw] OR "JNJ 28431754"[tw] OR TA 7284[tw] OR Prominad[tw] OR 0SAC974Z85[EC/RN Number] 301
#17 Search Canagliflozin[mesh] 144
#16 Search sodium-glucose transporter 2 inhibitor*[tw] OR sodium-glucose cotransporter 2 inhibitor*[tw] OR sodium-glucose co-transporter 2 inhibitor*[tw] OR sodium-glucose co-transporter 2 inhibitor*[tw] OR SGLT-2 inhibitor*[tw] OR SGLT2 inhibitor*[tw] OR sodium dependent glucose transporter 2 inhibitor*[tw] OR sodium dependent glucose cotransporter 2 inhibitor*[tw] OR sodium dependent glucose transporter 2 inhibitor*[tw] OR sodium dependent glucose co-transporter 2 inhibitor*[tw] OR gliflozin[tw] OR gliflozins[tw] 890
#15 Search "sodium glucose transporter 2/antagonists and inhibitors"[MeSH Terms] 515
#14 Search sitagliptin[tw] OR "EC 690-730-1"[tw] OR Glactiv[tw] OR "HSDB 7516"[tw] OR januvia or "mk 0431"[tw] OR mk0431[tw] OR "mk 431"[tw] OR "ono 5435"[tw] OR ristaben[tw] OR sitagliptine[tw] OR tesabel[tw] OR tesavel[tw] OR xelevia[tw] OR TS63EW8X6F[EC/RN Number] 1464
#13 Search Sitagliptin Phosphate[mesh] 812
#12 Search saxagliptin[tw] OR BMS 477118[tw] OR BMS477118[tw] OR HSDB 8199[tw] OR Onglyza[tw] OR "OPC 262"[tw] OR 9GB927LAJW[EC/RN Number] 410
#11 Search linagliptin[tw] OR "BI 1356"[tw] OR ONDERO[tw] OR tradjenta[tw] OR trajenta[tw] OR trayenta[tw] OR trazenta[tw] OR 3X29ZEJ4R2[EC/RN Number] 374
#10 Search Linagliptin[mesh] 194
#9 Search DPP4 inhibitor*[tw] OR DPP 4 inhibitor*[tw] OR DPP IV inhibitor*[tw] OR dipeptidyl-peptidase IV inhibitor*[tw] OR dipeptidyl-peptidase 4 inhibitor*[tw] OR gliptin[tw] OR gliptins[tw] OR alogliptin[tw] OR nesina[tw] OR "SYR 322"[tw] OR SYR322[tw] OR "HSDB 8203"[tw] OR incresina[tw] OR vipidia[tw] OR JHC049LO86[EC/RN Number] 3682
#8 Search Dipeptidyl-Peptidase IV Inhibitors[mesh] 2171
#7 Search antidiabetic*[tw] OR anti-diabetic*[tw] OR antihyperglycemic*[tw] OR antihyperglycaemic*[tw]OR anti-hyperglycemic*[tw] OR anti-hyperglycaemic*[tw] OR hypoglycemic*[tw] OR hypoglycaemic*[tw] OR antidiabetes*[tw] OR anti-diabetes*[tw] 67826
#6 Search Hypoglycemic Agents[mesh] 50724
#5 Search "diabetes mellitus, type 2/drug therapy"[MeSH] AND (Drug Combinations[mh:noexp] OR Drug Therapy, Combination[mh:noexp]) 3005
#4 Search #1 OR #2 OR #3 195943
#3 Search MODY[tw] OR NIDDM[tw] OR T2DM[tw] 17648
#2 Search (adult[tw] OR ketosis-resistant[tw] OR matur*[tw] OR late[tw] OR non-insulin depend*[tw] OR noninsulin depend*[tw] OR slow[tw] OR stable[tw] OR "type 2"[tw] OR "type II"[tw] lipoatrophic[tw]) AND diabet*[tw] 158
#1 Search ("Diabetes Mellitus, Type 2" [mesh] OR Diabetes Mellitus [mh:noexp]) 191490

Type 2 DM – Metformin/Canagliflozin, Albiglutide
Strategy
2016 Mar 31

OVID Multifile

Database: Embase Classic+Embase <1947 to 2016 March 30>, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1946 to Present>
Search Strategy:

--------------------------------------------------------------------------------

1 exp Diabetes Mellitus, Type 2/ (268256)
2 Diabetes Mellitus/ (561448)
3 ((adult or ketosis-resistant or matur* or late or non-insulin depend* or noninsulin depend* or slow or stable or type 2 or type II or lipoatrophic) adj3 diabet*).tw,kw. (277265)
4 (MODY or NIDDM or T2DM).tw,kw. (45587)
5 or/1-4 (851545)
6 (metformin adj3 canagliflozin).tw,kw. (30)
7 (invokamet or vokanamet).tw,kw. (12)
8 (albiglutide or albugon or (albumin adj1 GLP 1) or (albumin adj1 glucagon like peptide 1) or eperzan or "gsk 716155" or "gsk 716155a" or gsk716155 or gsk716155a or naliglutide or syncria or tanzeum).tw,kw. (336)
9 or/6-8 (375)
10 5 and 9 (337)
11 (controlled clinical trial or randomized controlled trial).pt. (496201)
12 clinical trials as topic.sh. (175547)
13 (randomi#ed or randomly or RCT$1 or placebo*).tw. (1673008)
14 ((singl* or doubl* or trebl* or tripl*) adj (mask* or blind* or dumm*)).tw. (330353)
15 trial.ti. (352103)
16 or/11-15 (2106806)
17 10 and 16 (146)
18 exp Animals/ not (exp Animals/ and Humans/) (14033037)
19 17 not 18 (60)
20 Adolescent/ not (exp Adult/ and Adolescent/) (1005985)
21 exp Child/ not (exp Adult/ and exp Child/) (2902402)
22 exp Infant/ not (exp Adult/ and exp Infant/) (1551113)
23 or/20-22 (3688845)
24 19 not 23 (60)
25 (comment or editorial or interview or news or newspaper article).pt. (1635966)
26 (letter not (letter and randomized controlled trial)).pt. (1832764)
27 24 not (25 or 26) (60)
28 27 use prmz (34)
29 diabetes mellitus/ (561448)
30 non insulin dependent diabetes mellitus/ (268072)
31 lipoatrophic diabetes mellitus/ (434)
32 ((adult or ketosis-resistant or matur* or late or non-insulin depend* or noninsulin depend* or slow or stable or type 2 or type II or lipoatrophic) adj3 diabet*).tw,kw. (277265)
33 (MODY or NIDDM or T2DM).tw,kw. (45587)
34 or/29-33 (851605)
35 canagliflozin plus metformin/ (11)
36 (invokamet or vokanamet).tw,kw. (12)
37 (invokamet or vokanamet).tw,kw. (12)
38 albiglutide/ (426)
39 (albiglutide or albugon or (albumin adj1 GLP 1) or (albumin adj1 glucagon like peptide 1) or eperzan or "gsk 716155" or "gsk 716155a" or gsk716155 or gsk716155a or naliglutide or syncria or tanzeum).tw,kw. (336)
40 782500-75-8.rn. (349)
41 or/35-40 (590)
42 34 and 41 (539)
43 randomized controlled trial/ or controlled clinical trial/ (1035110)
44 exp "clinical trial (topic)"/ (186130)
45 (randomi#ed or randomly or RCT$1 or placebo*).tw. (1673008)
46 ((singl* or doubl* or trebl* or tripl*) adj (mask* or blind* or dumm*)).tw. (330353)
47 trial.ti. (352103)
48 or/43-47 (2302324)
49 42 and 48 (259)
50 exp animal experimentation/ or exp models animal/ or exp animal experiment/ or nonhuman/ or exp vertebrate/ (42337113)
51 exp human/ or exp human experimentation/ or exp human experiment/ (32897478)
52 51 not 51 (0)
53 49 not 52 (259)
54 exp Juvenile/ not (exp Adult/ and exp Juvenile/) (2109989)
55 53 not 54 (259)
56 editorial.pt. (900764)
57 letter.pt. not (letter.pt. and randomized controlled trial/) (1828274)
58 55 not (56 or 57) (255)
59 58 use emczd (222)
60 28 or 59 (256)
61 remove duplicates from 60 (225) [TOTAL UNIQUE RECORDS]
62 61 use prmz (34) [MEDLINE UNIQUE RECORDS]
63 61 use emczd (191) [EMBASE UNIQUE RECORDS]

***************************

Cochrane Library

Search Name: Type 2 Diabetes - New Drugs
Date Run:        31/03/16 15:25:06.757
Description:     2016 Mar 31 - Ottawa Heart Institute

ID Search Hits
#1 [mh "Diabetes Mellitus, Type 2"]      10503
#2 [mh ^"Diabetes Mellitus"]      2731
#3 ((adult or "ketosis-resistant" or matur* or late or ("non-insulin" next depend*) or (noninsulin next depend*) or slow or stable or "type 2" or "type II" or lipoatrophic) near/3 diabet*):ti,ab,kw      20075
#4 (MODY or NIDDM or T2DM):ti,ab,kw      2938
#5 [or #1-#4]      22308
#6  (metformin near/3 canagliflozin):ti,ab,kw      14
#7 (invokamet or vokanamet):ti,ab,kw      0
#8 (albiglutide or albugon or (albumin near/1 GLP 1) or (albumin near/1 "glucagon like peptide 1") or eperzan or "gsk 716155" or "gsk 716155a" or gsk716155 or gsk716155a or naliglutide or syncria or tanzeum):ti,ab,kw      44
#9 [or #6-#8]      58
#10 #5 and #9        56

CENTRAL - 53

 

Research Team

George A. Wells, PhD1,2

Shannon Kelly, MSc1

Li Chen, MSc1

Ronald J. Sigal, MD, MPH, FRCPC3

Amy Johnston, MSc1

Shuching Hsieh, PhD1

Annie Bai, MD, MSc1

Jesse Elliott, MSc1

Wenfei Liu, BSc. DDS1

Becky Skidmore, MLIS4

1 Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, ON
2 University of Ottawa, Ottawa, ON
3 Julia McFarlane Diabetes Research Centre, Division of Endocrinology and Metabolism, University of Calgary, Calgary, AB
4 Independent Systematic Reviews Information Specialist, Ottawa, ON

 

About this Document

Cite as: Drugs for type 2 diabetes – project protocol. Ottawa: CADTH; 2016 Aug. (CADTH therapeutic review; vol.4, no.1a).

This report is prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). The report contains a comprehensive review of the existing public literature, studies, materials, and other information and documentation (collectively the “source documentation”) available to CADTH at the time of report preparation.

The information in this report is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this document to ensure that its contents are accurate, complete, and up to date as of the date of publication, CADTH does not make any guarantee to that effect. CADTH is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document or in any of the source documentation.

This document and the information provided are prepared and intended for use in the context of the Canadian health care system. Other health care systems are different; the issues and information related to the subject matter of this document may be different in other jurisdictions and, if used outside of Canada, it is at the user’s risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.

CADTH takes sole responsibility for the final form and content of this document, subject to the limitations noted above. The statements and conclusions in this document are those of CADTH and not of its advisory committees and reviewers. The statements, conclusions, and views expressed herein do not necessarily represent the views of Health Canada or any Canadian provincial or territorial government. Production of this document is made possible by financial contributions from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Prince Edward Island, Saskatchewan, and Yukon.

Copyright © 2016 CADTH. This report may be reproduced for non-commercial purposes only and provided that appropriate credit is given to CADTH.

ISSN: 1929-7440

PROSPERO REGISTRATION: CRD42016038144