(VP026) COMPARED TO INSULIN GLARGINE, TIRZEPATIDE REDUCES THE PREVALENCE OF THE METABOLIC SYNDROME IN PATIENTS WITH TYPE 2 DIABETES AND HIGH CARDIOVASCULAR RISK: POST-HOC ANALYSIS OF SURPASS-4

Background: The metabolic syndrome (MetS) is a confluence of risk factors that together amplify the risk for major cardiovascular adverse events. Tirzepatide (TZP), a glucose-dependent insulinotropic polypeptide/ glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, reduced individual risk factors of the MetS, for example glycemic control, weight, lipid levels and blood pressure, more than titrated daily insulin glargine (IGlar) in SURPASS-4. We compared effects of TZP and IGlar on the prevalence of MetS.

METHODS AND RESULTS: We assessed MetS in patients with type 2 diabetes and high cardiovascular risk. MetS was defined as having 3 or more of 5 criteria according to the National Cholesterol Education Program. Statistical analysis was based on on-treatment data at 52 weeks from patients taking ≥75% study drug. A logistic regression model with MetS status (Y/N) at 52 weeks as the response variable with MetS status (Y/N) at the baseline visit as an adjustment and randomized treatment as fixed explanatory effect was used in analysis. At baseline, the prevalence of MetS was 83-88% across groups with a significant dose-dependent reduction to 51-60% at 52 weeks in patients treated with TZP compared to no change (82%) with IGlar (p < 0.001; Table 1). All 5 individual risk factors of MetS were also reduced to a greater extent with TZP treatment compared to IGlar. The waist circumference risk factor prevalence at 52 weeks was 58-64% with TZP and 82% with IGlar.

Conclusion: This data supports an improvement in metabolic health with TZP treatment.