Key result
BMI <27 with prediabetes post-MI linked to ~20% higher MACE risk vs BMI ≥27 with normoglycemia.
Why the study?
In patients with a recent MI without diabetes, data on the prevalence of BMI <27 kg/m2 combined with prediabetes and its impact on progression to T2D and MACE are lacking.
Does BMI <27 kg/m2 combined with prediabetes increase the risk of progression to T2D and MACE in patients with a recent MI without diabetes compared to BMI ≥27 kg/m2 and normoglycemia?
Cohort (n=14,919)
Does BMI <27 kg/m2 combined with prediabetes increase the risk of progression to T2D and MACE in patients with a recent MI without diabetes compared to BMI ≥27 kg/m2 and normoglycemia?
Patients with a recent MI, BMI <27 kg/m2, and prediabetes have a significantly higher risk of developing T2D and MACE compared to those with BMI ≥27 kg/m2 and normoglycemia, highlighting a high-risk subgroup not currently recommended for semaglutide.
Identifies high-risk post-MI subgroup with low BMI plus prediabetes; leaves open whether semaglutide benefits extend beyond current BMI ≥27 criteria.
Background In the Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial, semaglutide reduced progression to type 2 diabetes (T2D) and major adverse cardiovascular events (MACE) in patients with a recent myocardial infarction (MI), a body mass index (BMI) ≥27 kg/m2, and without diabetes. However, in similar patients with a BMI <27 kg/m2, semaglutide is not recommended according to guidelines. Although 67% of patients in the SELECT trial had prediabetes, its prevalence and impact in clinical care patients remain unknown. Further, data on the prevalence of BMI <27 kg/m2 combined with prediabetes and the impact on the T2D and MACE risk following a recent MI are lacking. Purpose To investigate the prevalence of BMI <27 kg/m2 combined with prediabetes and the 5-year risk of progression to T2D and MACE in a cohort of patients with a recent MI without diabetes. Methods This cohort study included patients without diabetes who underwent coronary angiography due to a first-time MI between January 1, 2010 and December 31, 2021. Apart from not all having BMI ≥27 kg/m2, the patients met the SELECT trial eligibility criteria. Patients were stratified by BMI into <27 kg/m2 (lowest: 20 kg/m2) or ≥27 kg/m2, and by glycemic status based on HbA1c levels: <39 mmol/mol (normoglycemia) or 39-47 mmol/mol (prediabetes). Progression to T2D was defined as meeting any of these criteria during follow-up: a hospital diagnosis of diabetes, a HbA1c ≥48 mmol/mol, or redemption of a prescription for any diabetes medication. MACE were defined as a composite of MI, ischemic stroke, and cardiac death. Adjusted hazard ratios (aHRs) with 95% confidence interval (95% CI) were computed using Cox regression. Results The cohort comprised 14,919 patients with a median follow-up of 4.8 years (Q1-Q3: 2.8-5.0). Median BMI was 24 kg/m2 among those with a BMI <27 kg/m2, and 29 kg/m2 for those with a BMI ≥27 kg/m2. The prevalence of prediabetes was 44% among patients with a BMI <27 kg/m2 and 51% among those with a BMI ≥27 kg/m2 (Table). The 5-year risk of progression to T2D ranged from 2.1% to 30.0%, being highest in those with prediabetes, while the risk of MACE ranged from 8.9% (BMI ≥27 kg/m2 and normoglycemia) to 13.9% (BMI <27 kg/m2 and prediabetes; Table and Figure). BMI <27 kg/m2 combined with prediabetes (semaglutide currently not recommended) was associated with a four-fold higher rate of progression to T2D (aHR 4.33, 95% CI 3.57-5.25) and a 20% increased rate of MACE (aHR 1.20, 95% CI 1.02-1.41), compared with patients with BMI ≥27 kg/m2 and normoglycemia (semaglutide recommended). Conclusion In patients with a recent MI without diabetes, BMI <27 kg/m2 combined with prediabetes is highly prevalent and a strong predictor of progression to T2D and risk of MACE when compared with patients having BMI ≥27 kg/m2 and normoglycemia. The optimal treatment strategy for this novel, high-risk subgroup warrants further investigation.
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Tonnesen et al. (2025) conducted a cohort in Recent myocardial infarction without diabetes (n=14,919). BMI <27 kg/m2 combined with prediabetes vs. BMI ≥27 kg/m2 and normoglycemia was evaluated on Major adverse cardiovascular events (composite of MI, ischemic stroke, and cardiac death) (HR 1.20, 95% CI 1.02-1.41). In patients with a recent MI without diabetes, BMI <27 kg/m2 combined with prediabetes was associated with a higher rate of MACE compared with BMI ≥27 kg/m2 and normoglycemia (HR 1.20; 95% CI 1.02-1.41).
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