Effect of Dapagliflozin on the Progression From Prediabetes to T2DM in Subjects With Myocardial Infarction

The term prediabetes has been coined to describe an intermediate stage in the transition in glucose tolerance from normal glucose tolerance to overt diabetes. According to the ADA criteria, prediabetes include subjects with impaired fasting glucose (FPG=100-125 mg/dl) and/or impaired glucose tolerance (IGT, 2h-hour plasma glucose after 75 glucose load=140-199 mg/dl). Subjects with prediabetes manifest greater risk of progression to T2DM. The annual conversion rate from prediabetes (IFG/IGT) to T2DM varies among various ethnic groups and ranges between 7-15% . The worldwide estimated prevalence of prediabetes is 25-30% of adult population. The high prevalence of prediabetes and the high rate of progression from prediabetes to T2DM is the principal factor which fuels the worldwide diabetes epidemic.

The strong association between T2DM and risk of cardiovascular disease (CVD) is very well established. T2DM patients without established CVD manifest similar risk of acute myocardial infarction (MI) and death to non-diabetic patients with established CVD . Many epidemiologic studies have demonstrated that the close association between CVD risk and glucose intolerance extends to the prediabetic range. Thus, subjects with prediabetes manifest greater CVD risk than NGT. Since the deterioration in glucose tolerance from NGT, to prediabetes and T2DM is a continuum, the greater risk of CVD in subjects with prediabetes is no surprise. Indeed, numerous studies have documented progressive increase in CVD risk with the increase in the 2-hour plasma glucose concentration. In a meta analysis of 20 studies which included 95,783 patients followed for a mean of 12.4 years, an exponential correlation between CV risk and 2-hour plasma glucose concentration existed, and this relationship extended to the NGT range of 2-hour plasma glucose concentration. When patients were dichotomized based upon the 2h plasma glucose concentration to NGT (2h PG<140 mg/dl) and IGT (2h PG=140-199 mg/dl), IGT subjects consistently manifested greater risk of CVD. The increase in CVD risk in IGT subjects varied in different ethnic groups and ranged from 25-122%. These results collectively suggest a strong relationship between T2DM, prediabetes and CVD risk.

Study Aims and Goals:

The primary aim of the study is to examine the impact of SGLT2 inhibitor on T2DM and cardiovascular risk in patients with prediabetes and cardiovascular disease.

Objectives of this study: