Sitagliptin improves beta-cell function in patients with acute coronary syndromes and newly diagnosed glucose abnormalities-the BEGAMI study

Hage C, Brismar K, Efendic S, Lundman P, Ryden L, Mellbin L (Department of Medicine, Karolinska Institutet; Department of Molecular Medicine and Surgery, Karolinska Institutet; Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden). Sitagliptin improves beta-cell function in patients with acute coronary syndromes and newly diagnosed glucose abnormalities-the BEGAMI study. J Intern Med 2013; 273: 410-421. Background Newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) are common in patients with acute coronary syndrome (ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta-cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase-4 inhibitor initiated soon after a coronary event improves beta-cell function. Methods Acute coronary syndromeACS patients with IGT or T2DM (n=71), screened by oral glucose tolerance test (OGTT) 423days (median 6days) after hospital admission, were randomly assigned to sitagliptin 100mg (n=34) or placebo (n=37) and treated for a duration of 12weeks. All patients received lifestyle advice but no glucose-lowering agents other than the study drug. The study end-point was beta-cell function assessed using the insulinogenic index (IGI=Insulin30/Glucose30), derived from an OGTT, and acute insulin response to glucose (AIRg) assessed by a frequently sampled intravenous glucose tolerance test. Results The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4pmolmmol1 and 1394 vs. 1106pmol L1min1 respectively). After 12weeks, the IGI was 85.0 in the sitagliptin and 58.1pmol/mmol in the placebo group (P=0.013) and AIRg was 1909 and 1043pmolL1min1 (P<0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1mmolL1 in sitagliptin-treated patients and 6.0mmolL1 in those who received placebo compared with 5.8 and 5.9mmolL1 respectively, after 12weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin-treated patients compared with the placebo group (P=0.003). Sitagliptin was well tolerated. Conclusion Sitagliptin improved beta-cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances.