Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Nonglycemic Outcomes in Patients with Type 2 Diabetes

Abstract

The efficacy of the sodium‐glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal‐protecting benefits. Furthermore, during the landmark Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA‐REG OUTCOME) trial, a substantial reduction in major adverse cardiovascular outcomes was demonstrated with empagliflozin therapy. In view of the complex pathogenesis of cardiovascular disease in patients with diabetes, a pharmacologic intervention for type 2 diabetes that produces a multifaceted reduction in cardiovascular disease risk, separate from glycemic control alone, would be advantageous. Although SGLT2 inhibitors are generally well tolerated, they are associated with an increased risk of genital mycotic infections, as well as the potential risk for serious adverse events such as dehydration, development of diabetic ketoacidosis, serious urinary tract infections, and bone fractures. The findings of ongoing research will help to determine the magnitude and clinical importance of these adverse events and whether the findings of EMPA‐REG OUTCOME represent a class effect for SGLT2 inhibition or are specific to empagliflozin and will further elucidate the future role of SGLT2 inhibitors in the individualized management of patients with type 2 diabetes. In this article, we discuss the nonglycemic outcomes associated with SGLT2 inhibitor therapy in patients with type 2 diabetes as well as the clinical implications of these agents.

Effects of sodium‐glucose cotransporter 2 inhibitors on hypoglycaemia in brittle diabetic patients with decreased endogenous insulin secretion

“…The levels of serum total cholesterol and serum high‐density lipoprotein cholesterol also rose slightly but significantly. However, these were variations within the normal ranges, so their therapeutic significances were unclear . The changes in eGFR, however, suggest that hyperfiltration had been corrected.…”

“…There were also seven subjects with hyperthyroidism and three with hypothyroidism, but their symptoms were all being controlled to euthyroid status. In consideration of the characteristics of SGLT2Is, patients with an eGFR of <60 mL/min/1.73 m 2 were excluded from the study …”

“…In consideration of the characteristics of SGLT2Is, patients with an eGFR of <60 mL/min/1.73 m 2 were excluded from the study. 22 We decided not to change the amount of insulin until the end However, two withdrew their informed consent, six had insufficient data [had missing values for self-monitoring of blood glucose (SMBG)], and two discontinued medication (one did so because of frequent occurrence of serious hypoglycaemia, and one temporarily withdrew the drug because of cystitis). In the end, thirty individuals were recruited as analysis subjects.…”

Initiating therapy in patients newly diagnosed with type 2 diabetes: Combination therapy vs a stepwise approach

“…glucagon‐like peptide‐1 receptor agonists [GLP‐1RAs]) have multiple mechanisms of action while others (e.g. sodium‐glucose co‐transporter‐2 [SGLT2] inhibitors) are associated with novel mechanisms of action . In addition, a number of studies have shown potential beneficial effects of antihyperglycaemic drugs on the preservation of β‐cell function and mass, including incretin‐based therapies (e.g.…”

“…[SGLT2] inhibitors) are associated with novel mechanisms of action. 35 In addition, a number of studies have shown potential beneficial effects of antihyperglycaemic drugs on the preservation of β-cell function and mass, including incretin-based therapies (e.g. GLP-1RAs, dipeptidyl peptidase-4 [DPP-4] inhibitors), as well as thiazolidinediones (TZDs).…”