Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis

Jul 7, 2023Medicine

Comparing how well and how safely different glucagon-like peptide 1 drugs treat type 2 diabetes

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Abstract

Evidence from 12 studies involving 6213 patients indicates varying efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control.

Once-weekly GLP-1 receptor agonists significantly reduced hemoglobin A1c levels compared to placebo.
Semaglutide 2.0mg demonstrated the greatest glucose-lowering effect among the GLP-1RA regimens.
Other effective regimens included Semaglutide 1.0mg, Dulaglutide 4.5mg, and several lower doses of Semaglutide and Dulaglutide.
The GLP-1RA treatments showed a comparable safety profile regarding hypoglycemia.
All long-acting GLP-1RAs, except PEX168, had lower rates of gastrointestinal events like diarrhea, nausea, and vomiting compared to placebo.

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INTRODUCTION: This study aimed to evaluate the clinical efficacy and safety of 4 weekly formulations of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control, including glycemic control, by using a network meta-analysis (NMA).

METHODS: PubMed, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched from inception until June 10, 2022. Randomized clinical trials (RCTs) enrolling participants with diabetes mellitus type 2 and a follow-up of at least 12 weeks were included, for which 4 eligible GLP-1RAs Exenatide, Dulaglutide, Semaglutide, Loxenatide were compared with either each other or placebo. The primary outcome is the change of hemoglobin A1c level. Secondary outcomes including additional glycemic control indicators and adverse events (AE). Frequentist random-effect NMA were conducted for effect comparison. This meta-analysis was registered on PROSPERO, CRD42022342241.

RESULTS: The NMA synthesized evidence from 12 studies covering 6213 patients and 10 GLP-1RA regimens. A pairwise comparison of glycosylated hemoglobin type A1C () lowering effects showed that once-weekly GLP-1 receptor agonists were significantly better than placebo, and their glucose-lowering intensity was Semaglutide 2.0mg, Semaglutide 1.0mg, Dulaglutide 4.5mg, and Semaglutide 0.5mg, Dulaglutide 3.0mg, PEX168 200ug, Dulaglutide 1.5mg, PEX168 100ug and Dulaglutide 0.75mg. The GLP-1RA regimen has a comparable safety profile for hypoglycemia. And with the exception of PEX168, all other long-acting GLP-1RA drugs had lower rates of diarrhea, nausea and vomiting than placebo.

CONCLUSION: Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance.

Key numbers

−0.74%

Reduction with Semaglutide 2.0 mg

Standardized mean difference compared to placebo.

−5.51 kg

Weight Loss with Semaglutide 2.0 mg

Standardized mean difference compared to placebo.

3.91

Incidence of Hypoglycemia

Odds ratio compared to placebo.

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Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis

Abstract

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