Effects of Tirzepatide in Type 2 Diabetes: Individual Variation and Relationship to Cardiometabolic Outcomes.

BACKGROUND

Tirzepatide-a dual GIP/GLP-1 receptor agonist-exerts pleiotropic effects on cardiometabolic health.

OBJECTIVES

The authors sought to investigate the efficacy of tirzepatide in improving different cardiometabolic risk factors across individuals and subpopulations.

METHODS

Using an independent, global data-sharing and analytics platform, we performed an individual participant data meta-analysis by pooling data from 7 Phase 3 randomized clinical trials that compared tirzepatide with placebo or standard antihyperglycemic agents in individuals with type 2 diabetes. The study outcomes were the presence of a range of cardiometabolic abnormalities, representing components of metabolic syndrome (MetS) (elevated waist circumference, triglycerides, blood pressure, and fasting blood glucose, and decreased high-density lipoprotein cholesterol), as well as elevated body mass index and MetS (≥3 cardiometabolic abnormalities). Outcomes were modeled using mixed-effects models, with inverse probability weighting to account for study design differences.

RESULTS

We included 7,805 participants with a weighted median age of 59 years (Q1-Q3: 51-66 years) and 43.2% women. Over a weighted median treatment duration of 41.0 weeks, tirzepatide reduced the odds of all cardiometabolic abnormalities, ranging from 34% reduction for the odds of decreased high-density lipoprotein cholesterol (OR: 0.66 [95% CI: 0.52-0.84]) to 96% reduction in the odds of elevated body mass index (OR: 0.04 [95% CI:0.02-0.08]), and 72% reduction for the odds of MetS (OR: 0.28 [95% CI: 0.24-0.33]). Tirzepatide's superior efficacy in resolving MetS was consistent across demographic and clinical subpopulations, with higher efficacy in age <65 years vs ≥65 years, and in individuals without vs with baseline use of sodium-glucose cotransporter 2 inhibitors (P for interaction = 0.008 and 0.009, respectively).

CONCLUSIONS

This pooled analysis suggests that tirzepatide may improve cardiometabolic abnormalities and resolve MetS in individuals with type 2 diabetes.