Abstract Introduction Key elements in the management of prediabetes include the treatment of obesity and the appropriate management of dyslipidaemia and hypertension. Tirzepatide (TZP) is a once weekly GIP/GLP-1 receptor agonist approved for the treatment of obesity. In the SURMOUNT-1 3-year trial, participants with obesity and prediabetes treated with TZP achieved a mean weight reduction of up to 22.9%, which was accompanied by improvements in cardiometabolic risk factors and 94.5% had reverted to normoglycemia at week 176. Purpose The objective of this post hoc analysis was to evaluate the proportion of participants who met the combined clinically relevant goal of weight reduction 5%, systolic blood pressure (SBP) reduction 5 mmHg and non-HDL cholesterol reduction 10% from baseline to Week 176 in SURMOUNT-1 3-year trial. Methods Post hoc analyses included 568 participants with obesity and prediabetes who completed treatment with TZP (n=454) or placebo (n=114) at Week 176 and had measures for all three outcomes of weight, blood pressure and lipids or had any of the three measurements not meeting the threshold. Comparison of baseline characteristics was based on ANOVA model for continuous data and on Chi-square test for categorical data. Shifts in HbA1c (5.7% and ≥5.7%), BMI (≤27 and 27 kg/m²) and waist to height ratio (WHtR) categories (0.53 and ≥0. 53) from baseline to Week 176 were also calculated for those who met the combined clinical goals. Results A total of 145 (25.5%) participants met the combined goal at Week 176. Participants meeting vs. not meeting the combined goal had higher mean SBP (130.0 vs. 124.4 mmHg), total cholesterol (203.6 vs. 186.1 mg/dL), non-HDL cholesterol (155.4 vs. 138.2 mg/dL), LDL cholesterol (123.0 vs, 108.7 mg/dL), and triglycerides (175.2 vs. 148.8 mg/dL) at baseline. Significantly more TZP-treated participants (n=139, 30.6%) met the combined goal vs. placebo participants (n=6, 5.3%), p0.0001. Moreover, 94.2% (n=131) of TZP participants who met the combined goal also had an HbA1c 5.7% (Figure 1), while 41.0% (n=57) had a BMI ≤27 kg/m² and 28.8% (n=40) had a WHtR 0.53 (Figure 2). Of the six placebo participants who met the combined goal, all also had HbA1c 5.7%, while 1 had a BMI ≤27 kg/m² and 1 had a WHtR of 0.53. Conclusion In this post hoc analysis, treatment with TZP in participants with obesity and prediabetes was associated with significantly more participants achieving a combined clinical goal of weight reduction 5%, SBP reduction 5 mmHg and non-HDL cholesterol reduction 10% compared to placebo. Furthermore, the majority of TZP participants meeting the combined goal also achieved normoglycemia as defined by HbA1c 5.7%, more than 1 in 3 participants met the BMI goal, and 1 in 4 participants met the WHtR goal suggesting a reduction in central adiposity. Outcomes trials are ongoing to further evaluate the cardiometabolic impact of tirzepatide.
Sattar et al. (2025) studied this question.