Dataset Information

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis.

ABSTRACT:

Aims

To determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes mellitus.

Methods

Electronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and a mean body mass index ? 25 kg/m2. Pair-wise meta-analyses and mixed treatment comparisons were conducted to examine the difference in weight change at six months between the glucagon-like peptide-1 receptor agonists and each comparator.

Results

In the mixed treatment comparison (27 trials), the glucagon-like peptide-1 receptor agonists were the most successful in terms of weight loss; exenatide 2 mg/week: -1.62 kg (95% CrI: -2.95 kg, -0.30 kg), exenatide 20 ?g: -1.37 kg (95% CI: -222 kg, -0.52 kg), liraglutide 1.2 mg: -1.01 kg (95%CrI: -2.41 kg, 0.38 kg) and liraglutide 1.8 mg: -1.51 kg (95% CI: -2.67 kg, -0.37 kg) compared with placebo. There were no differences between the GLP-1 receptor agonists in terms of weight loss.

Conclusions

This review provides evidence that glucagon-like peptide-1 receptor agonist therapies are associated with weight loss in overweight or obese patients with type 2 diabetes with no difference in weight loss seen between the different types of GLP-1 receptor agonists assessed.

SUBMITTER: Potts JE

PROVIDER: S-EPMC4487255 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis.

Potts Jessica E JE Gray Laura J LJ Brady Emer M EM Khunti Kamlesh K Davies Melanie J MJ Bodicoat Danielle H DH

PloS one 20150629 6

<h4>Aims</h4>To determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes mellitus.<h4>Methods</h4>Electronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and ...[more]

PMID: 26121478

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Project description:BackgroundComparative effectiveness of 7 glucagon-like peptide 1 (GLP-1) agents on weight loss (WL) in obesity remains unknown.MethodsWe performed a systematic review, network meta-analysis (NMA) utilizing the following data sources: MEDLINE, EMBASE, Scopus, Cochrane Central and clinical trial registries, from inception to March 2, 2021. The prespecified criteria for study inclusion were randomized clinical trials (RCTs) of ≥12 weeks' duration. The data appraisal and extraction were performed by two investigators independently, using the published reports. The main outcomes and statistical methods were weight loss over placebo (WLOP) and adverse events (AEs) among GLP-1 agents using random-effects NMA (frequentist approach); relative ranking using surface under the cumulative ranking (SUCRA) method and certainty of evidence using grading of recommendations, assessment, development and evaluations (GRADE).Findings64 RCTs (from 2004 to 2021) included 27018 patients (median of age, 55.1 years old; 57.4% women; baseline weight 94.8kg and BMI 33.0kg/m2; trial duration 26 weeks). Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide ≥1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide ≤1.8mg; -4.49kg (-5.26 to -3.72) with liraglutide >1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ <2.4mg; -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg; -2.73kg (-4.81 to -0.65) with semaglutide oral; and -1.71kg (-2.64 to -0.78) with taspoglutide. Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg (SUCRAs 100, 86.1, 82.8 respectively). Highest SUCRAs for discontinuation due to AEs were with taspoglutide and liraglutide >1.8mg. Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%). Heterogeneity (I2 >50%) in WL and AEs reflected magnitude, not direction of effect.

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:Aims/introductionGlucagon-like peptide-1 receptor agonists (GLP-1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP-1Ras on fat distribution.Materials and methodsPubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP-1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis.ResultsA total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP-1Ras groups showed reductions in VAT (standard mean difference -0.54, 95% confidence interval [CI] -0.92, -0.17, I2 = 79%, P = 0.005) and SAT (standard mean difference -0.44, 95% CI -0.60, -0.27, I2 = 44%, P < 0.00001). In addition, bodyweight (weighted mean difference -3.59, 95% CI -4.30, -2.88, I2 = 0%, P < 0.00001), waist circumference (weighted mean difference -3.09, 95% CI -4.66, -1.52, I2 = 70%, P = 0.0001) and body mass index (weighted mean difference -1.11, 95% CI -1.35, -0.86, I2 = 47%, P < 0.00001) were significantly decreased. According to the Grades of Recommendation, Assessment, Development and Evaluation approach, the level of evidence was low or moderate.ConclusionThis study highlights that GLP-1Ras, especially liraglutide and exenatide, might play an active role in fat distribution in patients with type 2 diabetes. After treatment with GLP-1Ras, both VAT and SAT decreased, and the decrease of VAT was numerically greater than that of SAT.

Dataset Information

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis.

Aims

Methods

Results

Conclusions

Publications

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis.

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