Dataset Information

Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research.

ABSTRACT:

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety.

Objective

Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed.

Methods

A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D.

Results

Of the 1303 papers identified, 57 met the prespecified criteria for a high-quality clinical trial or retrospective study. The efficacy and tolerability of approved GLP-1RAs (exenatide twice daily or once weekly, dulaglutide, liraglutide, lixisenatide, and albiglutide) were compared with insulin products (23 prospective studies + seven retrospective studies), dipeptidyl peptidase-4 inhibitors (11 prospective studies + three retrospective studies), sulfonylureas (nine prospective studies + one retrospective study), thiazolidinediones (five prospective studies), and metformin (two prospective studies). GLP-1RAs are effective as a second-line therapy in improving glycemic parameters in patients with T2D. Reductions in glycated hemoglobin from baseline with GLP-1RAs tended to be greater or similar compared with insulin therapy. GLP-1RAs were consistently more effective in reducing body weight than most oral glucose-lowering drugs and insulin and were associated with lower hypoglycemia risk versus insulin or sulfonylureas. GLP-1RAs improved cardiovascular risk factors, and preliminary data suggest they improve cardiovascular outcomes in patients with T2D compared with oral glucose-lowering drugs. However, results from ongoing studies are awaited to confirm these early findings.

Conclusion

This systematic review found that GLP-1RAs are an effective class of glucose-lowering drugs for T2D.

SUBMITTER: Levin PA

PROVIDER: S-EPMC5389657 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research.

Levin Philip A PA Nguyen Hiep H Wittbrodt Eric T ET Kim Seoyoung C SC

Diabetes, metabolic syndrome and obesity : targets and therapy 20170404

<h4>Background</h4>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety.<h4>Objective</h4>Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed.<h4>Methods</h4>A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering ...[more]

PMID: 28435305

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Project description:BackgroundGlucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.PurposeThe purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.Data sourcesThe PubMed and EMBASE databases were searched up to November, 1st 2023.Study selectionWe selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.Data extractionTwo authors independently extracted the data.Data synthesisTwenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced Cmax and delayed tmax of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.LimitationsThe major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).ConclusionsTo conclude, reduced Cmax and delayed tmax of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .

Project description:BackgroundTo date, no studies have addressed the comparative efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) therapy on body composition and anthropometric indices among adult overweight or obese patients with or without type 2 diabetes. To provide evidence-based recommendations, we will conduct a traditional pairwise and network meta-analysis of all available randomized clinical trials that evaluated the effects of GLP1-RAs interventions for adult overweight or obese patients with or without type 2 diabetes.Methods and designElectronic databases, including Medline, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, and CINAHL, will be searched from inception without language restriction. Grey literature will be searched, including Google Scholar, ongoing clinical trial registries, and preprint reports. Reference lists of included trials, relevant major endocrinology scientific meetings, and manual hand searches from key general medicine and obesity and endocrinology journals will also be browsed. Two authors will screen, select, extract, appraise the risk of bias, and rate the evidence findings. Any disagreement will be resolved through team discussion. Based on a random-effects model, we will employ a two-step approach of traditional pairwise meta-analysis and network meta-analysis for quantitative synthesis. The pooled effect estimates using a frequentist approach with 95% confidence intervals for continuous endpoints will be expressed as the standardized mean difference, whereas odds ratios will be used for categorical endpoints. The quality of included trials will be evaluated using the Cochrane risk-of-bias version 2 assessment tool. Certainty of evidence for each outcome will be assessed using the modified confidence in network meta-analysis approach and the Grading of Recommended Assessment, Development, and Evaluation approach. The magnitude of the effect size, prediction intervals, surface under the cumulative ranking curve values, and certainty of evidence will be incorporated to draw evidence-based conclusions.ConclusionThis systematic review and network meta-analysis will summarize the comparative efficacy of GLP1-RAs therapy on body composition and anthropometric indices. Evidence identified from this review will promote the rational use of interventions for adult overweight or obese patients with or without type 2 diabetes and will serve as an important step for evidence-based practice within this area.Trial registrationPROSPERO registration number: CRD42023458228.

Project description:BackgroundPrevious meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications.MethodsWe searched PubMed, Scopus, and clinicaltrials.gov (inception-July 2019) for randomized controlled trials ≥ 52 weeks' duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506).ResultsForty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80-0.90), macrovascular complications (including stroke, RR 0.86, 0.78-0.95), and mortality (RR 0.89, 0.84-0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons.DiscussionGLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.

Dataset Information

Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research.

Background

Objective

Methods

Results

Conclusion

Publications

Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research.

Similar Datasets

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