Diabetes and hypertension are chronic diseases. They often coincide in the same patients and enhance the risk of cardiovascular and renal complications in a multiplicative manner. As one of the main regulators in glucose homeostasis, sodium glucose cotransporter 2 (SGLT2) is expressed in the proximal tubule of the nephron and facilitates glucose reabsorption from glomerulus along the nephron. Based on this function, several SGLT2 inhibitors (SGLT2i) were developed as a novel class of antidiabetic drugs, including empagliflozin, dapagliflozin, catagliflozin, ertugliflozin, and sotagliflozin. By far, totaled 10 RCTs involving 68,916 patients have been performed that tested the long-term outcomes associated with SGLT2i use. In five RCTs where all the patients enrolled had heart failure history (n = 21947), 87.9% were hypertensive and 76.3% were diabetic. Following a median of 0.8 to 2.3 years of treatment, HRs were 0.72 (0.67, 0.78) for first hospitalization for heart failure, 0.87 (0.79, 0.95) for cardiovascular death, and 0.92 (0.86, 0.99) for all-cause death. In another meta-analysis on five RCTs (n = 43467) that mainly recruited type 2 diabetic patients with uncontrolled hyperglycemia, more than 87% were hypertensive. After a median of 1.5 to 4.2 years of follow up, HRs were 0.87 (0.82, 0.93) for major adverse cardiovascular endpoints (MACE), 0.68 (0.62, 0.75) for heart failure, 0.82 (0.72, 0.93) for cardiovascular death, 0.87 (0.79, 0.96) for myocardial infarction, and 0.61 (0.56, 0.67) for worsening chronic kidney disease. The risk of heart failure and chronic kidney disease, but not MACE, decreased with more blood pressure lowering. Nevertheless, stricter glycemic control was associated with higher heart failure risk, but unrelated to MACE or chronic kidney disease. When dissecting the dosage effects of catagliflozin on lipid profiles, the results of a meta-analysis using 12 RCTs indicated that canagliflozin 100 mg or 300 mg significantly reduced systolic and diastolic blood pressure, but increased LDL and HDL cholesterol in a dose-dependent effect. Taken together, SGLT2i could reduce cardiovascular risk in diabetic and non-diabetic patients. The impact of SGLT2i on metabolic traits needs further investigation.
