Achieving glycemic targets is challenging, and responsiveness to therapy may diminish over time in T2D. Semaglutide, a new once-weekly GLP-1 analog for T2D treatment, showed superior reductions in HbA1c and body weight (BW) in SUSTAIN 1-5 and 7 clinical trials vs. placebo or active comparators. This meta-analysis assessed the efficacy and safety of semaglutide 0.5 mg and 1.0 mg according to diabetes duration.
Pooled efficacy data in 3,066 subjects were analyzed by T2D duration (≤5 [1,174], >5 to ≤10 [988] and >10 years [904]). Semaglutide consistently reduced HbA1c (1.4-1.8%) and BW (3.8-5.8 kg) from baseline comparably across subgroups (Figure).
The proportion of subjects on semaglutide (both doses) vs. comparators reporting AEs was 69.6% (≤5 years), 69.9% (>5 to ≤10 years) and 73.5% (>10 years) vs. 65.9, 70.8 and 69.0%. Serious AEs were reported by 6.2, 7.2 and 8.3% vs. 6.6, 6.0 and 6.3% respectively. Nausea was reported by 20.5, 20.7 and 20.1% vs. 9.3, 9.1 and 9.5%; vomiting by 9.4, 7.2 and 8.7% vs. 4.5, 4.2 and 4.3% subjects receiving semaglutide vs. comparators, respectively. Premature treatment discontinuation due to AEs was reported by 7.7, 7.9 and 8.5% vs. 3.6, 3.6 and 4.6% with semaglutide vs. comparators.
In conclusion, semaglutide consistently reduced HbA1c and BW, regardless of diabetes duration. AE reporting with semaglutide was unaffected by diabetes duration.
J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. L.B. Chaykin: Advisory Panel; Self; Intarcia Therapeutics, Inc. J. Luedemann: Other Relationship; Self; Novo Nordisk Inc., Eli Lilly and Company. S. Madsbad: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Eli Lilly and Company. Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi-Aventis, Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. J.F. Larsen: Employee; Self; Novo Nordisk A/S. E. Yildirim: Employee; Self; Novo Nordisk A/S. S.C. Bain: Research Support; Self; Novo Nordisk Inc., AstraZeneca.