Cardiovascular Effects of Sodium Glucose Co-transporter-2 Inhibitors in Patients with Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM), the leading type of diabetes, has a typical association with coronary heart disease. In India, patients with diabetes are at an increased risk of developing coronary disease as compared to people without diabetes and this suggests the requirement of intensive treatment of cardiovascular (CV) risk factors. Consequently, there is a need for an intervention that could target CV risk factors in multiple paths beyond hyperglycemic control alone. Although metformin is the mainstay of treatment in most of the patients with T2DM, a second line of treatment with anti-hyperglycemic agent is warranted in patients with T2DM in the management of CV risk factors beyond glycemic control. Sodium glucose co-transporter-2 (SGLT-2) inhibitors, the oral hypoglycemic drug, that act independent of insulin secretion are associated with a reduced risk of hypoglycemia which is associated with the increased risk of CV events. Moreover, it has been observed that the use of SGLT-2 inhibitors in patients with T2DM is associated with reductions in blood pressure and body weight beyond improved glycemic control. In this article, the clinical efficacy, safety, and tolerability of SGLT-2 inhibitors on glycemic, nonglycemic parameters, and CV outcome including data from the EMPA-REG OUTCOME study are discussed. The EMPA-REG OUTCOME study is the first CV outcome study that demonstrated the association of a glucose lowering agent with the reduced CV mortality and all-cause mortality, and reduced hospitalization for heart failure in patients with T2DM at high risk of CV events. Although the mode of action associated with the CV benefits remains unknown, data from ongoing trials including DECLARE-TIMI (Dapagliflozin Effect on CV Events) and CANVAS (Canagliflozin CV Assessment Study) trials potentially can validate the class-effect for SGLT-2 inhibitors regarding the CV outcomes.

Keywords: Cardiovascular benefits; sodium glucose co-transporter-2 inhibitors; type 2 diabetes mellitus.

Figure 1

Asian Indian phenotype that predispose to develop diabetes and coronary heart disease

Figure 2

Potential cardiovascular effects of sodium glucose co-transporter-2 inhibitors

Figure 3

Renal glucose reabsorption before and after sodium glucose co-transporter-2 inhibition

Figure 4

β-cell glucose sensitivity before and after treatment with dapagliflozin

Figure 5

Better three -item composite endpoint of clinical benefit (glycemia, weight and SBP) with Dapagliflozn compared to placebo