Dapagliflozin Reduces Diabetes and Heart Failure Risk Post-MI, Especially in Prediabetic and Obese Patients: Study

The DAPA-MI trial had previously established the cardiometabolic benefits of dapagliflozin in individuals who had suffered a heart attack and did not have type 2 diabetes at baseline. In this detailed subanalysis led by Professor Robert F. Storey and colleagues from the University of Sheffield, researchers aimed to explore whether initial glycemic status and BMI influenced the efficacy.

Out of 4,017 original participants, 3,425 met eligibility criteria for the subanalysis. These individuals were grouped according to their hemoglobin A1c levels—classified as normoglycemic (A1c <5.7%) or prediabetic (A1c between 5.7% and 6.5%)—and by BMI categories: normal weight, overweight, and obese.

The study revealed the following notable findings:

• Among individuals with normal blood sugar at baseline, 0.6% of those on dapagliflozin developed type 2 diabetes, compared to 1.6% in the placebo group
• In the prediabetic group, 10.1% of patients on dapagliflozin developed diabetes, versus 13.1% on placebo.
• This reflected a 26% relative risk reduction in diabetes onset among prediabetic individuals.
• Dapagliflozin reduced the occurrence of NYHA class III–IV heart failure symptoms, especially in those with prediabetes.
• In participants with both prediabetes and obesity, the absolute risk reduction for severe heart failure symptoms over one year was 10%
• The drug also supported weight loss, independent of glycemic status or BMI category.

These findings suggest that initiating sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as dapagliflozin, soon after a heart attack may offer substantial protective benefits—even in individuals without pre-existing diabetes or chronic heart failure. This is particularly relevant for patients with borderline blood sugar levels or excess weight.

While the results are promising, the authors acknowledge certain limitations. These include the post-hoc subgroup definitions, short follow-up duration, and low event rates, which may limit the generalizability of findings related to long-term cardiovascular outcomes.

"The subanalysis reinforces the potential of dapagliflozin as an early intervention to curb the onset of diabetes and reduce heart failure burden after myocardial infarction—especially in high-risk individuals with metabolic vulnerabilities," the authors concluded.

Reference:

Storey RF, Deanfield J, James S, Ajjan RA, Eriksson N, Erlinge D, de Belder M, Gale CP, Zaman A, Hofmann R, Mellbin L, Andersen K, Jiang Y, Johansson PA, Ridderstråle W, Langkilde AM, Parvaresh Rizi E, Oldgren J, McGuire DK. Impact of Dapagliflozin on Cardiometabolic Outcomes After Acute Myocardial Infarction According to Baseline Glycemic Status and Body Mass Index: Subanalyses of the DAPA-MI Trial. J Am Heart Assoc. 2025 Aug 5;14(15):e040327. doi: 10.1161/JAHA.124.040327. Epub 2025 Jul 29. PMID: 40728174.