Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data

It is well established that patients with type 2 diabetes mellitus (T2DM) are at increased risk of cardiovascular (CV) disease [1,2]. In addition to the chronic elevations in plasma glucose that contribute to increased CV risk [3,4], patients with T2DM often have comorbid conditions--such as obesity, hypertension, and dyslipidemia--that further contribute to the development of CV complications. As an example, the National Health and Nutrition Examination Survey (1999-2002) [5] revealed that patients with diabetes had mean body mass index (BMI) of 31.8 kg/m2, more than half reported having hypertension, and more than one third had dyslipidemia. Epidemiologic studies have shown a relationship between increasing levels of glycated hemoglobin (HbA1c) or fasting plasma glucose levels and the increased risk of CV complications, including coronary heart disease, chronic heart failure, and stroke; an association has also been shown between HbA1c levels and all-cause mortality [3,4].Despite these epidemiologic findings, evidence for the benefit of improved glycemic control on CV events and mortality in patients with T2DM remains mixed. The 10 years of primary follow-up from the landmark UK Prospective Diabetes Study (UKPDS) [6] and 3 recent outcome studies (the Action to Control Cardiovascular Risk in Diabetes [ACCORD], Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation [ADVANCE] and Veterans Affairs Diabetes Trial [VADT]) all individually failed to demonstrate that intensive glycemic control reduces CV events and mortality. However, a subsequent meta-analysis increased the statistical power of these studies by combining them with the results of the PROactive trial [7] and was able to show that intensive glycemic control significantly reduces coronary events compared with standard glycemic control, without an increased risk of death [8]. Moreover, an additional 10-year follow-up from the UKPDS demonstrated a benefit of inte