Dataset Information

A Network Meta-Analysis Comparing Semaglutide Once-Weekly with Other GLP-1 Receptor Agonists in Japanese Patients with Type 2 Diabetes.

ABSTRACT:

Introduction

Semaglutide once-weekly (QW) is a novel glucagon-like peptide-1 (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to-head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs) in a Japanese population, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of semaglutide QW vs GLP-1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on the comparison between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW.

Methods

A systematic review (SR) and supplementary Japanese searches were conducted to identify trials of GLP-1 RAs in Japanese patients on diet and exercise, who have previously received 0-1 oral antidiabetic drugs (OADs). Data at 52-56 weeks were extracted for the following outcomes (feasible for analysis in an NMA): glycated hemoglobin (HbA_1c), fasting plasma glucose (FPG), weight, systolic blood pressure (SBP), and overall hypoglycemia. The data were synthesized using an NMA and a Bayesian framework.

Results

Four trials, identified from the SR and Japanese-specific searches, were relevant for inclusion in the NMA. When compared to dulaglutide 0.75 mg QW, semaglutide 0.5 mg QW was shown to provide significant reductions in HbA_1c [- 0.61% (12.3 mmol/mol)], weight (- 1.45 kg), SBP (- 5.03 mmHg), and FPG (- 1.26 mmol/L). No significant differences in the proportion of patients achieving a HbA_1c level < 7% (53 mmol/mol) or the risk of overall hypoglycemia were observed between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW.

Conclusion

Overall, semaglutide 0.5 mg QW was associated with significant reductions from baseline in HbA_1c, weight, SBP, and FPG compared with dulaglutide 0.75 mg QW in Japanese patients with T2DM. These data may provide valuable evidence for clinical decision-making, cost-effectiveness analyses, and health technology appraisal (HTA) requirements.

Funding

Novo Nordisk Pharma Ltd.

SUBMITTER: Webb N

PROVIDER: S-EPMC5984907 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionOnce-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.MethodsA 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 (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework.ResultsIn 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 HbA1c (- 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 HbA1c 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.ConclusionOnce-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c 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.FundingNovo Nordisk.

Project description:AimsTo assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).MethodsIn this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks.ResultsOverall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001).ConclusionsIn Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

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