Evidence-Based Clinical Review on Cardiovascular Benefits of SGLT2 (Sodium-Glucose Co-Transporter Type 2) Inhibitors in Type 2 Diabetes Mellitus

Cardiovascular (CV) diseases are the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (DM). Therefore, there has been an increasing endorsement from diabetic associations across the globe for the use of anti-diabetic drugs, which not only provide not only glycemic control but also have cardioprotective effects. Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are one class of drugs that have shown evidence of CV benefits in patients with type 2 DM. We reviewed the published literature and found five adequately powered clinical trials that evaluated the CV effects of SGLT2 inhibitors in type 2 DM patients. These trials assessed the CV effect of three SGLT2 inhibitors, namely, empagliflozin, canagliflozin, and dapagliflozin. It was found that all these clinical trials were multi-centric and conducted in and after 2015 across different parts of the World, enrolling type 2 DM patients with varied baseline characteristics in terms of age, BMI, sex, glomerular filtration rate, history of existing renal diseases, etc. In spite of these differences, the SGLT2 drugs were found to be beneficial by significantly reducing all-cause mortality, mortality due to CV causes, and risk of major CV events. All the studies highlighted the cardioprotective effect of SGLT-2 inhibitors, especially empagliflozin, dapagliflozin, and canagliflozin in type 2 DM patients with established CV disease, but the studies could not find significant improvement in 3P-MACE (three-point major adverse CV event) indicators offered by these drugs except empagliflozin. Hence, adequately powered clinical trials with long follow-up durations are the need of the hour to address this issue specifically.