Weekly Semaglutide vs. Liraglutide Efficacy Profile: A Network Meta-Analysis

Abstract

Introduction: Glucagon-like peptide 1 receptor agonist (GLP-1 RA) is a class of hypoglycemic medications. Semaglutide once-weekly (QW) and liraglutide once-daily (OD) significantly improved glycemic control compared to placebo. To date, no long-term phase III trials directly comparing semaglutide and liraglutide are available. This network meta-analysis (NMA) aims to compare the long-term efficacy of semaglutide and liraglutide.

Methods: PubMed, Embase, and Cochrane Library were searched from inception until June 2019 to identify relevant articles. Nine long-term randomized controlled trials comparing once-weekly semaglutide or liraglutide with placebo or other active comparisons were identified. The outcomes of interest were changes in HbA1c and weight after 52 weeks. A Bayesian framework and NMA were used for data synthesis. This is a sub-study of the protocol registered in PROSPERO (number CRD42018091598).

Results: The data showed significant superiority in HbA1c reduction of semaglutide 1 mg QW over liraglutide 1.2 and 1.8 mg with a treatment difference of 0.47% and 0.3%, respectively. Semaglutide 0.5 mg QW was found to be significantly superior to liraglutide 1.2 mg in HbA1c reduction with a treatment difference of 0.17%. Regarding weight reduction analysis, semaglutide 0.5 and 1 mg QW were significantly associated with a greater reduction than liraglutide 0.6 mg with a treatment difference of 2.42 and 3.06 kg, respectively. However, no significant reduction was found in comparison to liraglutide 1.2 and 1.8 mg.

Conclusions: Semaglutide improved the control of blood glucose and body weight. The capacity of long-term glycemic control and body weight control of semaglutide appears to be more effective than other GLP-1 RAs, including liraglutide. However, considering the number of included studies and potential limitations, more large-scale, head-to-head, well-designed randomized-controlled trials (RCTs) are needed to confirm these findings.

Keywords: GLP-1; GLP-1 RA; Glucagon-like peptide; HbA1c; diabetes mellitus; glycemic control; liraglutide; network meta-analysis; semaglutide; weight.

Figure 1

Flowchart of studies considered for inclusion.

Figure 2

Evidence network of included studies for HbA1c analysis. Semaglutide 1 = Semaglutide 1 mg once-weekly (QW), Semaglutide 0.5 = Semaglutide 0.5 mg QW, Semaglutide 14 = oral semaglutide 14 mg, Glimpiride 4 = Glimepiride 4 mg, Glimpiride 8 = Glimepiride 8 mg, Liraglutide 0.6 = Liraglutide 0.6 mg once-daily (OD), Liraglutide 1.2 = Liraglutide 1.2 mg OD, Liraglutide 1.8 = Liraglutide 1.8 mg OD, Liraglutide 3 = Liraglutide 3 mg OD, OAD = Oral anti-diabetic drugs, Exenatide = Exenatide 2 mg, Sitagliptin = Sitagliptin 100 mg, HbA1c = glycated hemoglobin, Green: Low risk of bias, Yellow: Unclear risk of bias, Red: High risk of bias.

Figure 3

Evidence network of included studies for weight analysis. Semaglutide 1 = Semaglutide 1 mg once-weekly (QW), Semaglutide 0.5 = Semaglutide 0.5 mg QW, Glimpiride 4 = Glimepiride 4 mg, Glimpiride 8 = Glimepiride 8 mg, Liraglutide 0.6 = Liraglutide 0.6 mg once-daily (OD), Liraglutide 1.2 = Liraglutide 1.2 mg OD, Liraglutide 1.8 = Liraglutide 1.8 mg OD, Liraglutide 3 = Liraglutide 3 mg OD, OAD = Oral anti-diabetic drugs, Exenatide = Exenatide 2 mg, Sitagliptin = Sitagliptin 100 mg, Green: Low risk of bias, Yellow: Unclear risk of bias, Red: High risk of bias.

Figure 4

Forest plots of the NMA results: HbA1c outcomes for the primary comparators. The NMA results are presented as forest plots for a change from baseline in HbA1c. OR = treatment difference, LCL and UCL = lower and upper credible intervals (95% Crl) for mean treatment effect. Treatment differences are considered significant when the 95% CrI excludes 0. HbA1c = glycated hemoglobin, NMA = network meta-analysis.

Figure 5

Forest plots of the NMA results: weight outcomes for primary comparators. The NMA results are presented as forest plots for a change from baseline in weight. OR = treatment difference, LCL and UCL = lower and upper credible intervals (95% Crl) for mean treatment effect. Treatment differences are considered significant when the 95% CrI excludes 0. NMA = network meta-analysis.