Tirzepatide in Adults With Type 1 Diabetes: A Phase 2 Randomized Placebo-Controlled Clinical Trial.

OBJECTIVE: Overweight and obesity are prevalent in type 1 diabetes and contribute to cardiovascular risk. Tirzepatide, a gastric inhibitory polypeptide and glucagon-like peptide 1 receptor coagonist, has not been studied in type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a 12-week, phase 2, double-blind, placebo-controlled trial in adults with type 1 diabetes and BMI >30 kg/m2. Participants were randomized to once-weekly subcutaneous tirzepatide (2.5 mg for 4 weeks, 5.0 mg for 8 weeks) or placebo. The primary end point was change in body weight at 12 weeks. RESULTS: Twenty-two of 24 adults with type 1 diabetes completed the study. After 12 weeks, the mean change in weight was -10.3 kg (95% CI -12.8 to -7.7 kg) in the tirzepatide group and -0.7 kg (95% CI -1.4 to 2.8 kg) in the placebo group, with an estimated treatment difference of -8.7 kg (95% CI -12.0 to -5.5 kg; P < 0.0001), representing 8.8% weight loss. In the tirzepatide group, 100% and 45% of participants experienced weight loss of ≥5% and ≥10% respectively, compared with 9% and 0% in the placebo group. Tirzepatide improved HbA1c (mean difference -0.4% [95% CI -0.7 to 0.0%] vs. placebo; P = 0.05) and reduced total daily insulin dose (-24.2 units/day tirzepatide and -0.3 units/day placebo; difference from baseline vs. placebo -35.1% [95% CI -46.5 to -21.3%; P = 0.0002]). There were no significant adverse events in either group. CONCLUSIONS: Among adults with type 1 diabetes and obesity, tirzepatide was superior to placebo for weight loss over 12 weeks.