In the SURMOUNT-2 (SM-2) trial, adults with overweight/obesity and type 2 diabetes (T2D) treated with tirzepatide (TZP), which is a once-weekly GIP/GLP-1 receptor agonist, showed significant reduction in body weight when combined with a low-calorie diet and increased physical activity.

The current post-hoc study analyzed those participants who achieved composite endpoints at 72 weeks. The composite endpoint included blood pressure (BP) under 130/80 mm Hg, non-HDL cholesterol under 130 mg/dl, and three HbA1c levels under 7%, 6.5%, and 5.7%. Logistic regression with missing values imputed using a mixed model repeated measures approach assessed participants. This analysis used the efficacy estimand and compared participants who achieved the composite endpoints in the 10mg TZP group (N=312) and the 15mg TZP group (N=311) to the placebo group (N=315).

At baseline, participants had an average body weight 100.7 kg, BMI of 36.1 kg/m², HbA1c of 8.02%, BP of 130.5/79.8 mm Hg, and non-HDL cholesterol of 132.5 mg/dl.

In the 15mg TZP group, 33.8%, 32.8%, and 25.9% of participants met the composite endpoints compared to 7.5%, 3.9%, and 0.7% in the placebo group at 72 weeks (Fig). The 10mg TZP group had similar results to the 15mg group.

Figure: Proportion of participants achieving triple endpoint composite goals; BP goal < 130/80 mmHg, lipid goal non-HDL <130mg/dl and 3 HbA1c goals of <7%, <6.5% and <5.7% at 72 weeks.

Data are proportion (SE) of participants achieving triple endpoint. Abbreviations are TZP = tirzepatide, A1c = HbA1c, BP = Blood Pressure, HDL = High Density Lipoprotein, * indicates p < 0.001, TZP treatment versus PBO, based on the odds ratios for <7% HbA1c, 10mg: OR 5.7 (95% CI, 3.3, -9.7), 15mg: OR 6.8 (95% CI, 4.0, 11.6), <6.5% HbA1c, 10mg: OR 10.3 (95% CI, 5.25, 19.52), 15mg: OR 12.7 (95% CI, 6.60, 24.38), & <5.7% HbA1c, 10mg: OR 25.1 (95% CI, 7.21, 87.50), 15mg: OR 39.2 (95% CI, 11.32, 135.41).

In people with T2D and overweight/obesity, a higher proportion of participants receiving TZP achieved clinically meaningful composite endpoints. These endpoints included blood pressure, lipid levels, and HbA1c goals, compared to those on the placebo. This indicates that in addition to significant weight loss, TZP can help achieve multiple clinical goals, which is important for improving cardiometabolic health.

120-OR: American Diabetes Association (ADA) 84th Scientific Sessions, 2024, 21- 24 June 2024, Orlando, Florida.