Predicted 10-Year Cardiovascular Disease Risk Reduction with Tirzepatide Use Over Three Years for Primary Prevention of Cardiovascular Disease in Obesity

A post hoc analysis of SURMOUNT-1 found that tirzepatide, compared with placebo, lowered predicted 10-year cardiovascular disease risk over 176 weeks in adults with overweight/obesity and prediabetes, with the benefit persisting at 3 years. The Framingham-based risk-model estimate matched observed event reduction in the REWIND trial, but actual cardiovascular outcome data for tirzepatide are still awaited.

Journal article — post hoc analysis of phase 3 double-blind RCT. Population: Individuals with obesity/overweight and prediabetes from the SURMOUNT-1 trial. Sample size: 2,539 randomised; 962 in post hoc analysis. Follow-up: 176 weeks. Interventions: Tirzepatide (5 mg, 10 mg, 15 mg).

In 962 analysed participants, tirzepatide 15 mg was associated with a 10-year predicted CVD risk reduction at week 72 (ARR -1.92%), while placebo was associated with an absolute risk increase of 1.10% (p < 0.001; HR = 0.73). At week 176, tirzepatide was associated with an ARR of -1.31% and placebo with an ARI of 3.84% from baseline (p < 0.001; HR = 0.62). In REWIND, the HR for dulaglutide versus placebo from risk prediction was 0.83, consistent with the HR from observed cardiovascular events of 0.85. The authors concluded that tirzepatide was associated with a lower predicted 10-year CVD risk versus placebo over 3 years.

For researchers working on Tirzepatide, this paper suggests that tirzepatide's predicted 10-year CVD risk benefit is durable and that Framingham-based risk equations may approximate its effect on cardiovascular events. It does not establish actual cardiovascular event reduction; that requires ongoing event-driven trials such as SURMOUNT-MMO.

Key findings

• Tirzepatide 15 mg was associated with an absolute risk reduction of 1.92% in predicted 10-year CVD risk at week 72, while placebo was associated with an absolute risk increase of 1.10% (HR = 0.73).
• At week 176, tirzepatide-treated participants had an absolute risk reduction of 1.31%, whereas placebo had an absolute risk increase of 3.84% from baseline (HR = 0.62).
• In the REWIND trial, the model-derived HR for dulaglutide versus placebo was 0.83, consistent with the HR based on observed cardiovascular events of 0.85.
• The post hoc analysis included 962 SURMOUNT-1 participants with baseline and post-baseline predicted CVD risk scores, from 2,539 randomised participants.

Limitations

• Post hoc analysis of SURMOUNT-1 rather than a prespecified outcome.
• Predicted risk from the Framingham Heart Study equation, not recorded cardiovascular events.
• Includes only participants with prediabetes and without pre-existing CVD; results may not generalise.
• Confirmation in event-based cardiovascular outcomes trials such as SURMOUNT-MMO is still needed.

The record

• Journal: European journal of preventive cardiology: zwag408
• Published: 2026-08-10
• PMID: 42572119 — DOI: 10.1093/eurjpc/zwag408

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

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