5-year risk of progression to type 2 diabetes in patients with myocardial infarction and overweight or obesity: a cohort study of the preventive potential of semaglutide treatment

Abstract Background Semaglutide has demonstrated the ability to reduce the risk of progression to type 2 diabetes (T2D) and major adverse cardiovascular events (MACE) in patients with myocardial infarction (MI) and overweight or obesity without diabetes. However, implementation of semaglutide treatment in daily clinical care is challenging due to costs and limited supply. Thus, it is essential to identify patients who are most likely to benefit from this treatment. Purpose To investigate the 5-year risk of progression to T2D and MACE in patients with MI and overweight or obesity without diabetes, and to explore the preventive potential of semaglutide on reducing progression to T2D in daily clinical care. Methods This cohort study included patients with first-time MI and a body mass index (BMI) ≥27 kg/m2 without diabetes from the Western Denmark Heart Registry who met the eligibility criteria of the Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial. The cohort was grouped by glycemic status at baseline based on HbA1c: prediabetes 42-47 mmol/mol, prediabetes 39-47 mmol/mol, or normoglycemia (39 mmol/mol). Progression to T2D was defined as a first measured HbA1c ≥48 mmol/mol, a first redemption of a prescription for any diabetes medication, or a first hospital diagnosis of diabetes. MACE were defined as a composite of MI, ischemic stroke, and cardiovascular death. We used Cox regression to adjust for sex, age, hypertension, and smoking. The 5-year number-needed-to-treat (NNT5) by semaglutide treatment was estimated using the diabetes risk reduction observed in the SELECT trial. Results The cohort comprised 7,398 patients with a median follow-up of 4.7 years (Q1-Q3 2.8-5.0). At baseline, 1,385 (19%) patients had prediabetes 42-47 mmol/mol, 3,751 (51%) had prediabetes 39-47 mmol/mol, and 3,647 (49%) had normoglycemia. The median BMI was very similar at 30 kg/m2 (Q1-Q3 28-33), 30 kg/m2 (Q1-Q3 28-32), and 29 kg/m2(Q1-Q3 28-31), respectively. The 5-year risks of progression to T2D were 54% for patients with prediabetes 42-47 mmol/mol, 30% for those with prediabetes 39-47 mmol/mol, and 5% for those with normoglycemia (Table, Figure). Prediabetes 42-47 mmol/mol and 39-47 mmol/mol were associated with 18-fold and 8-fold higher rates of progression to T2D compared with normoglycemia (Table). NNT5 to prevent one case of T2D was 2.7 (95% CI: 2.5-2.8) for those with prediabetes 42-47 mmol/mol. The 5-year risks of MACE were similar at 11%, 11% and 9%, respectively (Table). Conclusions In patients with recent MI and overweight or obesity without diabetes, prediabetes 42-47 mmol/mol was strongly associated with progression to T2D, while the risk of MACE was not significantly elevated. Consequently, patients with prediabetes 42-47 mmol/mol represent a subgroup of the SELECT-eligible population, where the potential reduction of T2D makes semaglutide treatment more advantageous from a cost-benefit point of view.