Dataset Information

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis.

ABSTRACT:

Introduction

The present study aimed to evaluate the effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on clinical and safety outcomes including glycemic control and cardiometabolic indicators using network meta-analysis.

Methods

MEDLINE, Embase, and Cochrane Library Central Register of Controlled Trials were searched from inception through June 30, 2019. Randomized clinical trials comparing one or more of six eligible GLP-1RAs with placebo or another eligible GLP-1RA were identified. We further screened studies that had 24-30 week follow-up periods and target endpoints. The primary outcome was change in hemoglobin A_1c (HbA_1c). Secondary outcomes included additional glycemic control indicators, cardiometabolic measures, and adverse events. Frequentist random-effect network meta-analyses were conducted for effect comparison.

Results

The NMA synthesized evidence from 54 studies covering 23,209 patients and 18 GLP-1RA regimens. All included GLP-1RA regimens except liraglutide 0.3 mg once weekly (QW) significantly lowered HbA_1c after 24-30 weeks compared with placebo. The pairwise comparison of HbA_1c-lowering effect showed that dulaglutide 0.75 mg QW, dulaglutide 1.5 mg QW, exenatide 2 mg QW, liraglutide 0.9 mg QW, liraglutide 1.2 mg QW, liraglutide 1.8 mg QW, loxenatide 100 µg QW, and loxenatide 200 µg QW were not significantly outperformed by any of the other regimens. The effects on blood pressure, weight, and lipids were relatively mixed. The GLP-1RA regimens had comparable safety profiles with regard to hypoglycemia and adverse events.

Conclusion

Regimens of GLP-1RAs had differential glycemic control and cardiometabolic effectiveness. Policymaking and patient-centric clinical decisions should take into consideration the comparative effectiveness profiles.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC7932945 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis.

Jiang Yawen Y Liu Jia J Chen Xin X Yang Wenying W Jia Weiping W Wu Jing J

Advances in therapy 20210213 3

<h4>Introduction</h4>The present study aimed to evaluate the effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on clinical and safety outcomes including glycemic control and cardiometabolic indicators using network meta-analysis.<h4>Methods</h4>MEDLINE, Embase, and Cochrane Library Central Register of Controlled Trials were searched from inception through June 30, 2019. Randomized clinical trials comparing one or more of six eligible GLP-1RAs with placebo or another eligible GLP-1R ...[more]

PMID: 33582976

Similar Datasets

Project description:BackgroundThe cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA).MethodsMedline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA).ResultsA total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.ConclusionThe GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary.

Project description:ObjectiveTo synthesize current evidence of the impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on hypoglycemia, treatment discontinuation and glycemic level in patients with type 2 diabetes.DesignSystematic review and network meta-analysis.Data sourcesLiterature search (Medline, Embase, the Cochrane library), website of clinical trial, bibliographies of published systematic reviews.Eligibility criteriaRandomized controlled trials with available data comparing GLP-1 RAs with placebo or traditional anti-diabetic drugs in patients with type 2 diabetes.Data synthesisTraditional pairwise meta-analyses within DerSimonian-Laird random effects model and network meta-analysis within a Bayesian framework were performed to calculate odds ratios for the incidence of hypoglycemia, treatment discontinuation, HbA1c<7.0% and HbA1c<6.5%. Ranking probabilities for all treatments were estimated to obtain a treatment hierarchy using the surface under the cumulative ranking curve (SUCRA) and mean ranks.Results78 trials with 13 treatments were included. Overall, all GLP-1 RAs except for albiglutide increased the risk of hypoglycemia when compared to placebo. Reduction in the incidence of hypoglycemia was found for all GLP-1 RAs versus insulin (except for dulaglutide) and sulphonylureas. For the incidence of treatment discontinuation, increase was found for exenatide, liraglutide, lixisenatide and taspoglutide versus placebo, insulin and sitagliptin. For glycemic level, decrease was found for all GLP-1 RAs versus placebo. Dulaglutide, exenatide long-acting release (exe_lar), liraglutide and taspoglutide had significant lowering effect when compared with sitagliptin (HbA1c<7.0%) and insulin (HbA1c<6.5%). Finally, according to SUCRAs, placebo, thiazolidinediones and albiglutide had the best decrease effect on hypoglycemia; sulphanylureas, sitagliptin and insulin decrease the incidence of treatment discontinuation most; exe_lar and dulaglutide had the highest impact on glycemic level among 13 treatments.ConclusionsAmong 13 treatments, GLP-1 RAs had a significant reduction with glycemic level but a slight increase effect on hypoglycemia and treatment discontinuation. While albiglutide had the best decrease effect on hypoglycemia and treatment discontinuation among all GLP-1 RAs. However, further evidence is necessary for more conclusive inferences on mechanisms underlying the rise in hypoglycemia.

Project description:IntroductionThe cardiovascular efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) are well documented; however, the differences in cardiovascular efficacy among subpopulations remain unknown. This systematic review and meta-analysis aimed to explore the differences in cardiovascular efficacy of long-acting GLP-1RAs among subpopulations of patients with T2DM and to assess the drug safety.MethodsRelevant studies up to March 31, 2020 were searched for in six electronic databases, namely PubMed, Cochrane Library, Embase, Clinical Trials, Science Direct, and Web of Science. The primary outcome was three-point major adverse cardiovascular events (including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke). Subpopulations were defined using ten selected influential factors, and the differences in cardiovascular efficacy in subpopulations stratified by different influential factors were accessed by synthesizing studies with random-effects models one by one.ResultsA total of six cardiovascular outcome trials of long-acting GLP-1RAs, comprising 49,936 participants, were included. Among stratified subpopulations, no significant differences in the cardiovascular efficacy of long-acting GLP-1RAs were observed across the ten characteristics of subjects (all P for interaction > 0.05). Favorable trends were observed in the subpopulation with established cardiovascular disease (CVD) compared to that without (P = 0.171). With regards to safety, long-acting GLP-1RAs did not significantly increase the risk of retinopathy (OR 1.09; 95% CI 0.92-1.29; P = 0.316), but increase the risk of serious gastrointestinal events (OR 1.37; 95% CI 1.02-1.83; P = 0.037). Long-acting GLP-1RAs did not significantly increase the risk of serious adverse events (OR 0.92; 95% CI 0.85-1.00; P = 0.039).ConclusionsOur analysis suggested no subpopulation differences in the cardiovascular efficacy of long-acting GLP-1RAs among stratified subpopulations, and favorable trends were only observed in the subpopulation with established CVD. These findings may have implications for the management of long-acting GLP-1RAs across subpopulations of patients with T2DM.

Project description:Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy. Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo. Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

Project description:BackgroundGlucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin, a gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety.ObjectivesTo assess the effects of glucagon-like peptide analogues in patients with type 2 diabetes mellitus.Search strategyStudies were obtained from electronic searches of The Cochrane Library (last search issue 1, 2011), MEDLINE (last search March 2011), EMBASE (last search March 2011), Web of Science (last search March 2011) and databases of ongoing trials.Selection criteriaStudies were included if they were randomised controlled trials of a minimum duration of eight weeks comparing a GLP-1 analogue with placebo, insulin, an oral anti-diabetic agent, or another GLP-1 analogue in people with type 2 diabetes.Data collection and analysisData extraction and quality assessment of studies were done by one reviewer and checked by a second. Data were analysed by type of GLP-1 agonist and comparison treatment. Where appropriate, data were summarised in a meta-analysis (mean differences and risk ratios summarised using a random-effects model).Main resultsSeventeen randomised controlled trials including relevant analyses for 6899 participants were included in the analysis. Studies were mostly of short duration, usually 26 weeks.In comparison with placebo, all GLP-1 agonists reduced glycosylated haemoglobin A1c (HbA1c) levels by about 1%. Exenatide 2 mg once weekly and liraglutide 1.8 mg reduced it by 0.20% and 0.24% respectively more than insulin glargine. Exenatide 2 mg once weekly reduced HbA1c more than exenatide 10 μg twice daily, sitagliptin and pioglitazone. Liraglutide 1.8 mg reduced HbA1c by 0.33% more than exenatide 10 μg twice daily. Liraglutide led to similar improvements in HbA1c compared to sulphonylureas but reduced it more than sitagliptin and rosiglitazone.Both exenatide and liraglutide led to greater weight loss than most active comparators, including in participants not experiencing nausea. Hypoglycaemia occurred more frequently in participants taking concomitant sulphonylurea. GLP-1 agonists caused gastrointestinal adverse effects, mainly nausea. These adverse events were strongest at the beginning and then subsided. Beta-cell function was improved with GLP-1 agonists but the effect did not persist after cessation of treatment.None of the studies was long enough to assess long-term positive or negative effects.Authors' conclusionsGLP-1 agonists are effective in improving glycaemic control.

Project description:BackgroundGlucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs.MethodsMEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events.ResultsStudies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 ?g twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily.Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped.ConclusionsGLP-1 agonists are effective in improving glycaemic control and promoting weight loss.

Dataset Information

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis.

Introduction

Methods

Results

Conclusion

Publications

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets