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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

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Witkowski, Michal, Wilkinson, Lars, Webb, Neil, Weids, Alan, Glah, Divina, Vrazic, Hrvoje·2018·Diabetes Therapy
DOI 10.1007/s13300-018-0428-yPMC PMC5984931
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Abstract

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. 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. 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. 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. Novo Nordisk.

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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 HbA1c, weight, and FPG, the proportions of patients with HbA1c < 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. 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 HbA1c, weight, and FPG, the proportions of patients with HbA1c < 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-dailyCC BY-NC · PubMed Central
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 HbA1c, b proportion of patients achieving target HbA1c < 7% or c HbA1c ≤ 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, HbA1c 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 HbA1c, b proportion of patients achieving target HbA1c < 7% or c HbA1c ≤ 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, HbA1c glycated hemoglobin, LIRA liraglutide, LIXI lixisenatide, NMA network meta-analysis, QD once-daily, QW once-weeklyCC BY-NC · PubMed Central

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Metadata

Authors
Witkowski, M., Wilkinson, L., Webb, N., Weids, A., Glah, D., & Vrazic, H.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Novo Nordisk (United Kingdom) (GB)
Corresponding author
Webb, Neil
ORCID
Venue
Diabetes Therapy
Publisher
Springer Science and Business Media LLC
Published
2018-04-30
Volume
9
Issue
3
Pages
1233-1251
ISSN
  • 1869-6953 (ISSN-L)
  • 1869-6961
DOI
10.1007/s13300-018-0428-y
PMC
PMC5984931
OpenAlex
W2799276912
Cited by
18
References
7
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1
FWCI
0.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Therapy (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Novo Nordisk
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
Keywords
GLP-1 receptor agonists, type 2 diabetes, basal insulin, adjunctive therapy, HbA1c, HbA1c reduction, body weight, systolic blood pressure, nausea, liraglutide, drug comparison, dose comparison, glycemic control, adverse events

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