Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis

Abstract

Objective: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin.

Methods: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA_1c, weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (±4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity.

Results: Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0 mg and 0.5 mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA_1c for once-weekly semaglutide 1.0 mg vs SGLT-2is ranged from −0.66% for canagliflozin 300 mg (95% Credible Intervals [CrI]: −0.82, −0.50%) to −1.11% for dapagliflozin 5 mg (95% CrI: −1.37, −0.85%). Once-weekly semaglutide 1.0 mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data.

Conclusion: Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy.

Keywords:

• Once-weekly semaglutide
• type 2 diabetes
• glucagon-like peptide-1 analog
• GLP-1
• SUSTAIN 2
• SUSTAIN 7
• SGLT-2 inhibitors

Transparency

Declaration of funding

This publication was supported by Novo Nordisk A/S.

Declaration of financial/other interests

LW, HV, and SL are employees of Novo Nordisk. RS, EP, ED, and SK report funding was provided by Novo Nordisk to Precision Xtract, where they are employees. A CMRO peer reviewer on this manuscript declares they have been a trial investigator in Semaglutide studies. A CMRO peer reviewers on this manuscript declares they have received fees from Novo Nordisk for talks, advisory boards, and clinical trials, and have received research support from Novo Nordisk. All peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

We would like to thank Ziyu Zhang and Robyn Kendall for their contributions in the systematic literature review.