A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving Basal Insulin

Abstract

Introduction: Once-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin.

Methods: A systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA_1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework.

Results: In total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA_1c (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA_1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators.

Conclusion: Once-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA_1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs.

Funding: Novo Nordisk.

Keywords: Basal insulin; GLP-1 receptor agonist; Glycemic control; HbA1c; Network meta-analysis; Semaglutide; Systematic review; Systolic blood pressure; Type 2 diabetes; Weight.

Fig. 1

Evidence networks for all outcomes. Blue nodes indicate a primary intervention of interest, orange nodes indicate a primary comparator of interest, and gray nodes indicate a secondary comparator. a The evidence network for the change from baseline in HbA_1c, weight, and FPG, the proportions of patients with HbA_1c < 7% or ≤ 6.5%, and the incidence of nausea, vomiting, and diarrhea. b The evidence network for the change from baseline in SBP. c The evidence network for the proportion of patients with ≥ 5% weight loss. ALBI albiglutide, BID twice-daily, DULA dulaglutide, EXE exenatide, IGlu insulin glulisine, ILispro insulin lispro, LIRA liraglutide, LIXI lixisenatide, QD once-daily, QW once-weekly, SEMA semaglutide, TID thrice-daily

Fig. 2

Forest plots of the NMA results—once-weekly semaglutide 0.5 or 1.0 mg vs comparator. Treatment differences are considered significant when the 95% CrI excludes the null value. Odds ratios are considered significant when the 95% CrI excludes 1. The NMA results are presented as Forest plots for a change from baseline in HbA_1c, b proportion of patients achieving target HbA_1c < 7% or c HbA_1c ≤ 6.5%, d change from baseline in FPG, e change from baseline in weight, and the incidence of f nausea, g vomiting, and h diarrhea. ALBI albiglutide, BID twice-daily, CrI credible interval, DULA dulaglutide, EXE exenatide, FPG fasting plasma glucose, HbA_1c glycated hemoglobin, LIRA liraglutide, LIXI lixisenatide, NMA network meta-analysis, QD once-daily, QW once-weekly

Fig. 2

Forest plots of the NMA results—once-weekly semaglutide 0.5 or 1.0 mg vs comparator. Treatment differences are considered significant when the 95% CrI excludes the null value. Odds ratios are considered significant when the 95% CrI excludes 1. The NMA results are presented as Forest plots for a change from baseline in HbA_1c, b proportion of patients achieving target HbA_1c < 7% or c HbA_1c ≤ 6.5%, d change from baseline in FPG, e change from baseline in weight, and the incidence of f nausea, g vomiting, and h diarrhea. ALBI albiglutide, BID twice-daily, CrI credible interval, DULA dulaglutide, EXE exenatide, FPG fasting plasma glucose, HbA_1c glycated hemoglobin, LIRA liraglutide, LIXI lixisenatide, NMA network meta-analysis, QD once-daily, QW once-weekly

Fig. 2

Forest plots of the NMA results—once-weekly semaglutide 0.5 or 1.0 mg vs comparator. Treatment differences are considered significant when the 95% CrI excludes the null value. Odds ratios are considered significant when the 95% CrI excludes 1. The NMA results are presented as Forest plots for a change from baseline in HbA_1c, b proportion of patients achieving target HbA_1c < 7% or c HbA_1c ≤ 6.5%, d change from baseline in FPG, e change from baseline in weight, and the incidence of f nausea, g vomiting, and h diarrhea. ALBI albiglutide, BID twice-daily, CrI credible interval, DULA dulaglutide, EXE exenatide, FPG fasting plasma glucose, HbA_1c glycated hemoglobin, LIRA liraglutide, LIXI lixisenatide, NMA network meta-analysis, QD once-daily, QW once-weekly