May 1, 2026Diabetes and Vascular Disease Research0 citationsOpen Access

Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study

AQAbdul QadeerRawalpindi Medical University MKMarwah Bintay KhalidRawalpindi Medical University RSRidwan SyedThe University of Texas Medical Branch at Galveston

Structured PICO

Does tirzepatide reduce MACE and all-cause mortality compared to semaglutide in patients with obesity and type 2 diabetes?

Population

95,608 patients aged > 40 years or with obesity (BMI ≥ 30 kg/m2) and type 2 diabetes (HbA1c ≥ 6.5% or fasting glucose ≥ 125 mg/dL), mean age 75 years, 45% male, 74% white.

Intervention

Tirzepatide (at least three prescriptions, no prior exposure to comparator or other GLP-1 receptor agonists)

Comparator

Semaglutide (at least three prescriptions, no prior exposure to comparator or other GLP-1 receptor agonists)

Outcome

MACE and all-cause mortality within a 1-year windowcomposite

In a real-world cohort of patients with obesity and type 2 diabetes, tirzepatide was associated with lower risks of MACE, all-cause mortality, and better glycemic control compared to semaglutide over 1 year.

Abstract

BackgroundWith the increasing use of GLP-1 receptor agonists and dual GIP/GLP-1 agonists for managing obesity and type 2 diabetes, understanding their real-world effectiveness and safety is essential. This TriNetX analysis directly compares clinical outcomes among patients treated with tirzepatide vs semaglutide.MethodWe utilized data from the TriNetX Research Network, identifying patients aged > 40 years or with obesity ("BMI ≥ 30 kg/m2") and type 2 diabetes (HbA1c ≥ 6.5% or fasting glucose.≥ 125 mg/dL). Qualifying events were restricted to May 1, 2022, through November 21, 2024. We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists. The index date was defined as the first co-occurrence of the obesity/diabetes criteria and the respective drug prescription. To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort. Outcomes, including all-cause mortality, MACE, heart failure exacerbation, ischemic stroke/TIA, hospitalization/ED use, dementia, UTI, adverse Gastrointestinal (GI) effects, and changes in HbA1c, were assessed within a 1-year window after the index date.ResultsOur matched cohort had a mean age of 75 years, with 45% male patients and 74% identified as white. Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978). All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562). The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up. There was no significant difference in heart failure exacerbation or UTI incidence. GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997), while hospitalization or emergency visits were comparable between the two groups.ConclusionIn this propensity matched cohort of patients with obesity and type 2 diabetes, tirzepatide demonstrated improved cardiometabolic outcomes compared to semaglutide, including lower all-cause mortality and lower HbA1c. These findings support the cardiovascular safety and efficacy of tirzapetide and highlight the need for further studies to evaluate its effectiveness in broader clinical populations.

Ask AI

Helpful

Bookmark

View Full Paper