Benefits of SGLT2 Inhibitors Beyond Glycemic Control – A Focus on Metabolic, Cardiovascular and Renal Outcomes

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of Type 2 Diabetes Mellitus (T2DM). Objective: To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. Methods: A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin. A review of literature citations provided further references. The search identified 17 clinical trials and 2 meta-analyses with outcomes of weight loss and blood pressure reduction with dapagliflozin, canagliflozin, or empagliflozin. Three randomized trials focused on either empagliflozin or canagliflozin and reduction of cardiovascular disease and progression of renal disease. Results: SGLT2 inhibitors have a beneficial profile in the treatment of T2DM. They have evidence of reducing weight between 2.9 kilograms when used as monotherapy to 4.7 kilograms when used in combination with metformin, and reducing systolic blood pressure between 3 to 5 mmHg and reducing diastolic blood pressure approximately 2 mmHg. To date, reduction of cardiovascular events was seen specifically with empagliflozin in patients with T2DM and a history of cardiovascular disease. In the same population, empagliflozin was associated with slowing the progression of kidney disease. Moreover, patients with increased risk of cardiovascular disease treated with canagliflozin have decreased risk of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. Data regarding these outcomes with dapagliflozin are underway. Conclusion: SGLT2 inhibitors demonstrate some positive metabolic effects. In addition, empagliflozin specifically has demonstrated reduction in cardiovascular events and delay in the progression of kidney disease in patients with T2DM and a history of cardiovascular disease. Further data is needed to assess if this is a class effect.