Tirzepatide in Adults with Type 1 Diabetes– A Phase 2 Randomized Placebo-Controlled Clinical Trial

<p dir="ltr">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 co-agonist, 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 body mass index greater than 30 kg/m2. Participants were randomized to once-weekly subcutaneous tirzepatide (2.5mg for 4 weeks, 5.0mg for 8 weeks) or placebo. The primary endpoint 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% confidence interval [CI],-12.8 to -7.7kg) in the tirzepatide group and -0.7 kg (95%CI, -1.4 to 2.8kg) 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 greater than 5% and 10% respectively, compared to 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 (-24.2units/day tirzepatide and -0.3units/day placebo [difference -35.1% from baseline vs placebo, 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.</p>