Trial results for a heart disease study of oral semaglutide in patients with type 2 diabetes were posted on ClinicalTrials.gov on 2025-09-22. The study showed that participants receiving oral semaglutide experienced fewer major adverse cardiovascular events (MACE) compared to placebo, with 579 events versus 668, corresponding to a Hazard Ratio of 0.86 (p-value 0.0028).
Background
Semaglutide is a medication used in patients with Type 2 Diabetes Mellitus. This study investigated whether oral semaglutide could have a positive effect on heart disease outcomes in this patient population.
Trial design
The study (NCT03914326), titled 'A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes,' was a Phase 3 trial that enrolled 9651 participants. The trial investigated oral semaglutide tablets against a placebo in patients diagnosed with Type 2 Diabetes Mellitus. Participants were instructed to take one tablet daily on an empty stomach. The study duration was approximately 3.5-5 years.
Key results
The trial results indicated a reduction in major adverse cardiovascular events (MACE) with oral semaglutide. For the outcome of 'Number of Participants From Randomization to First Occurrence of a Major Adverse Cardiovascular Event (MACE), a Composite Endpoint Consisting of: Cardiovascular (CV) Death/Non-fatal Myocardial Infarction/Non-fatal Stroke':
- Participants in the Oral Semaglutide group experienced 579 events.
- Participants in the Placebo group experienced 668 events.
A Cox Regression analysis for this outcome yielded a Hazard Ratio (HR) of 0.86 (95.0% CI: 0.77 to 0.96) with a p-value of 0.0028.
Other key measurements also showed fewer events in the oral semaglutide group compared to placebo:
- For the composite endpoint of CV Death; Renal Death; Onset of Persistent ≥50% Reduction in eGFR; Onset of Persistent eGFR <15 mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy: 403 participants in the Oral Semaglutide group vs. 435 in the Placebo group.
- For CV Death: 301 participants in the Oral Semaglutide group vs. 320 in the Placebo group.
- For Major Adverse Limb Events (MALE): 71 participants in the Oral Semaglutide group vs. 99 in the Placebo group.
- For an Expanded MACE Composite Endpoint (CV Death/Non-fatal Myocardial Infarction/Non-fatal Stroke/Coronary Revascularisation/Unstable Angina Pectoris Requiring Hospitalisation): 670 participants in the Oral Semaglutide group vs. 777 in the Placebo group.
- For a Composite Endpoint of All-cause Death/Non-fatal MI/Non-fatal Stroke: 779 participants in the Oral Semaglutide group vs. 902 in the Placebo group.
What this means
The results of this Phase 3 study suggest that oral semaglutide significantly reduces the risk of major adverse cardiovascular events in patients with Type 2 Diabetes Mellitus. The consistent reduction across various cardiovascular and renal endpoints, including CV death and major adverse limb events, indicates a potential benefit of oral semaglutide beyond glycemic control for this patient population. These findings are important for clinicians managing cardiovascular risk in individuals with type 2 diabetes.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03914326, titled 'A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes,' were posted on 2025-09-22 on clinicaltrials.gov.