Long-term efficacy and safety of early sitagliptin initiation in individuals with type 2 diabetes: an extension of the SPIKE study.

Aims/instruction: We previously demonstrated that sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, slowed down the progression of carotid atherosclerosis in type 2 diabetes participants who were treated with insulin and had no history of cardiovascular disease in the Sitagliptin Preventive study of Intima-Media Thickness Evaluation (SPIKE) trial. This was an extension of the SPIKE trial that examined if early sitagliptin initiation improved long-term cardiovascular outcomes. Materials and methods: In the SPIKE trial, 282 participants were randomized to either sitagliptin or conventional treatment to examine the effects of sitagliptin on carotid atherosclerosis. All participants who completed the SPIKE trial were recruited to this prospective, observational, cohort study and followed for up to 520 weeks. The primary endpoint was the first occurrence of a major cardiovascular event, which included acute myocardial infarction, stroke, or total mortality. Results: Events of composite primary outcome occurred in only a few participants in each group (15 [12.6%] in the sitagliptin group and eight in the conventional treatment group [6.7%]). The incidence rate of the primary outcome did not differ significantly between two groups. In post hoc Poisson regression analysis, there were no significant between-group differences in the incidence rates of composite recurrence events for the same outcomes as the primary endpoint. Conclusions: Early initiation of sitagliptin as add-on therapy to insulin was not linked to reduced risk of composite cardiovascular disease. This may be due to low event numbers in both groups and/or relatively lower continuation rates of DPP-4 inhibitors in the sitagliptin group during the follow-up period. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00786-7.