Diabetes Trial Files: Tirzepatide for Obesity + Prediabetes, Tirzepatide in HF + Obesity, and Switching from Dulaglutide to Tirzepatide
Tirzepatide for Obesity Treatment and Diabetes Prevention
Jastreboff AM et al. NEJM (November 2024)
Bottom Line: This phase 3, double-blind, randomized, controlled trial evaluated the efficacy and safety of tirzepatide in 2539 participants with obesity, including 1032 with prediabetes, over a total of 193 weeks. Participants were assigned to receive tirzepatide at doses of 5 mg, 10 mg, or 15 mg, or placebo. The primary outcomes included percent change in body weight and onset of type 2 diabetes, with tirzepatide showing weight reductions of -12.3%, -18.7%, and -19.7% compared to -1.3% for placebo, and a significantly lower incidence of type 2 diabetes. Safety results indicated mild to moderate gastrointestinal adverse events, with no new safety signals identified.
Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity
Zile MR et al. Circulation (November 2024)
Bottom Line: This double-blind randomized clinical trial evaluated the efficacy of tirzepatide (titrated up to 15 mg SC weekly) versus placebo in 731 patients with class II to IV heart failure and obesity over a median duration of 104 weeks. The primary outcomes included the reduction in cardiovascular death or worsening heart failure and improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. Results showed a significant increase in Kansas City Cardiomyopathy Questionnaire score by 6.9 points (95% CI, 3.3-10.6) and 6-minute walk distance by 18.3 meters (95% CI, 9.9-26.7) for the tirzepatide group. The study concluded that tirzepatide led to meaningful improvements in heart failure management.
Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide
Billings LK et al. Annals of Internal Medicine (April 2025)
Bottom Line: This multicenter, randomized, open-label, phase 4 trial (SURPASS-SWITCH) evaluated the efficacy and safety of switching from dulaglutide to tirzepatide in adults with inadequately controlled type 2 diabetes. A total of 282 adults were enrolled, with 139 receiving tirzepatide (15 mg or MTD) and 143 receiving dulaglutide (4.5 mg or MTD). The primary outcome was change in HbA1c at week 40, showing a reduction of -1.44% with tirzepatide and -0.67% with dulaglutide, resulting in an estimated treatment difference of -0.77% (P < 0.001). Safety results indicated similar rates of serious adverse events between groups, with nausea and diarrhea being the most common.
Diabetes Trial Files Issue #DIA-2025-05
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