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 1–2 Oral Anti-Diabetic Drugs

Abstract

IntroductionOnce-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1–2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1–2 OADs.MethodsA systematic literature review (SLR) was conducted in order to identify trials of GLP-1 RAs in patients inadequately controlled on 1–2 OADs. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in a NMA), which included the key outcomes of change from baseline in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and weight, as well as discontinuation due to adverse events (AEs). Data were synthesized using a NMA and a Bayesian framework.ResultsIn total, 26 studies were included across the base case analyses. Once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c and weight vs all GLP-1 RA comparators. Once-weekly semaglutide 0.5 mg also achieved significantly greater reductions in HbA1c and weight compared with the majority of other GLP-1 RAs. Both doses of once-weekly semaglutide were associated with similar odds of discontinuation due to AEs compared with other GLP-1 RAs.ConclusionOverall, once-weekly semaglutide 1.0 mg as an add-on to 1–2 OADs is the most efficacious GLP-1 RA in terms of the reduction of HbA1c and weight from baseline after 6 months of treatment. In addition, the analysis suggests that once-weekly semaglutide is well tolerated and not associated with an increase in discontinuations due to AEs compared with other GLP-1 RAs.FundingNovo Nordisk.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0424-2) contains supplementary material, which is available to authorized users.

Semaglutide for type 2 diabetes mellitus: A systematic review and meta‐analysis

“…To our knowledge, this is the first systematic review and meta‐analysis to assess the totality of the available evidence base supporting use of semaglutide in everyday clinical practice. In line with our findings, an isolated industry‐funded network meta‐analysis, with a narrower scope, recently compared semaglutide to other GLP‐1 RAs and showed that semaglutide was superior in terms of HbA1c lowering and body weight reduction, with a similar risk of adverse effects . Similarly, an industry‐funded pooled analysis summarized existing evidence from a subset of SUSTAIN trials .…”

Evaluation of the long‐term cost‐effectiveness of once‐weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK

“…The SUSTAIN 8 trial (NCT03136484) will provide a head‐to‐head comparison of once‐weekly semaglutide with SGLT‐2 inhibitors (canagliflozin 300 mg). As well as in the SUSTAIN 7 trial (NCT02648204), once‐weekly semaglutide was compared with other GLP‐1 receptor agonists in the SUSTAIN 3 trial (exenatide extended‐release, NCT01885208) and in an NMA (liraglutide, dulaglutide, exenatide twice‐daily, exenatide extended‐release, lixisenatide and albiglutide) in which once‐weekly semaglutide was associated with greater reductions in HbA1c and body weight in all comparisons . Once‐weekly semaglutide was compared with basal insulin in the SUSTAIN 4 trial (NCT02128932) and was associated with significant improvements in HbA1c and body weight .…”

“…As well as in the SUSTAIN 7 trial (NCT02648204), once-weekly semaglutide was compared with other GLP-1 receptor agonists in the SUSTAIN 3 trial (exenatide extended-release, NCT01885208) and in an NMA (liraglutide, dulaglutide, exenatide twice-daily, exenatide extended-release, lixisenatide and albiglutide) in which once-weekly semaglutide was associated with greater reductions in HbA1c and body weight in all comparisons. 19,21 Once-weekly semaglutide was compared with basal insulin in the SUSTAIN 4 trial (NCT02128932) and was associated with significant improvements in HbA1c and body weight. 59 Additionally, sub-group analyses based on baseline HbA1c and BMI have shown that once-weekly semaglutide is consistently more efficacious than other treatment options included in the SUSTAIN trial programme in all sub-groups, rather than simply in groups with a high BMI at baseline.…”

“…The SUSTAIN clinical trial programme found that once‐weekly semaglutide was more efficacious in terms of both HbA1c and weight reduction than exenatide extended‐release and dulaglutide, with a similar side‐effect profile, in head‐to‐head studies . Additionally, a network meta‐analysis (NMA) has shown that once‐weekly semaglutide is more efficacious than other GLP‐1 receptor agonists …”

“…19,20 Additionally, a network meta-analysis (NMA) has shown that once-weekly semaglutide is more efficacious than other GLP-1 receptor agonists. 21 The SUSTAIN 7 clinical trial assessed the efficacy and safety of once-weekly semaglutide vs dulaglutide. 20 The SUSTAIN 7 trial was a 40-week, randomized, open-label trial comparing once-weekly semaglutide 0.5 mg with dulaglutide 0.75 mg, and comparing once-weekly semaglutide 1 mg with dulaglutide 1.5 mg.…”