84-LB: Efficacy and Safety of Tirzepatide vs. Semaglutide Once-Weekly as Add-On Therapy to Metformin in People with Type 2 Diabetes (SURPASS-2)

• Published in: Diabetes (New York, N.Y.) Vol. 70; no. Supplement_1
• Main Authors: FRIAS, JUAN PABLO, DAVIES, MELANIE J., ROSENSTOCK, JULIO, PEREZ MANGHI, FEDERICO C., LANDO, LAURA FERNANDEZ, BERGMAN, BRANDON, LIU, BING, CUI, XUEWEI, BROWN, KATELYN
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-06-2021
• Subjects: Antidiabetics; Body weight; Body weight loss; Diabetes; Diabetes mellitus (non-insulin dependent); GIP protein; Glucagon; Glucagon-like peptide 1; Glucose; Hypoglycemia; Metformin
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db21-84-LB

The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide (TZP) is in development for type 2 diabetes (T2D). Efficacy and safety of once weekly TZP vs. semaglutide (SEMA) was assessed in people with T2D on background metformin. In this open-label, 40-wk Phase 3 study, people with T2D (N=1879; mean baseline [BL] HbA1c 8.28%; age 56.6 y; T2D duration 8.6 y; BMI 34.2 kg/m2) were randomized (1:1:1:1) to TZP (5, 10, 15 mg) or SEMA (1 mg). Primary efficacy objective was noninferiority of TZP 10 and/or 15 mg vs. SEMA for mean change in HbA1c from BL at 40 wk. Secondary objectives included noninferiority (TZP 5 mg) for HbA1c change and superiority (all TZP doses) for change in HbA1c, body weight (BW) and fasting serum glucose (FSG), and proportion of patients with HbA1c <7%, ≤6.5% and <5.7% (except TZP 5 mg) and BW loss ≥5%, ≥10%, ≥15% at 40 wk. All TZP doses were superior to SEMA for change from BL in mean HbA1c, FSG, BW and in achieving all HbA1c and BW loss targets at 40 wk (Table). The most common AEs were gastrointestinal and mostly mild to moderate in severity. Clinically significant (blood glucose <54 mg/dL) or severe hypoglycemia events were low. In conclusion, all TZP doses demonstrated superior and clinically meaningful improvement in glycemic control and substantial weight loss vs. SEMA 1 mg in people with T2D treated with metformin.