The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic, complex metabolic disease characterized by chronic hyperglycemia causing from insufficient insulin signaling because of insulin resistance or defective insulin secretion, and may induce severe complications and premature death. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are oral drugs used to reduce hyperglycemia in patients with T2DM, including empagliflozin, ertugliflozin, dapagliflozin and canagliflozin. The primary objective of this article is to examine the clinical benefit, safety, and tolerability of the four SGLT2 inhibitors approved by the US FDA. SGLT2 inhibitors increase urinary glucose excretion via inhibiting SGLT2 to decrease renal reabsorption of filtered glucose and reduce the renal threshold for glucose. Rather than stimulating insulin release, SGLT2 inhibitors improve β-cell function by improving glucotoxicity, as well as reduce insulin resistance and increase insulin sensitivity. Early clinical trials have confirmed the beneficial effects of SGLT2 in T2DM with acceptable safety and excellent tolerability. In recent years, SGLT2 inhibitors has been successively approved by the FDA to decrease cardiovascular death and decrease the risk of stroke and cardiac attack in T2DM adults who have been diagnosed with cardiovascular disease, treating heart failure (HF) with reduced ejection fraction and HF with preserved ejection fraction, and treat diabetic kidney disease (DKD), decrease the risk of hospitalization for HF in T2DM and DKD patients. SGLT2 inhibitors are expected to be an effective treatment for T2DM patients with non alcoholic fatty liver disease. SGLT2 inhibitors have a similar safety profile to placebo or other active control groups, with major adverse events such as Ketoacidosis or hypotension and genital or urinary tract infections.

The Effects of Cardioprotective Antidiabetic Therapy on Microbiota in Patients with Type 2 Diabetes Mellitus—A Systematic Review

“…The SGLT-2i class inhibits glucose reabsorption in the proximal convoluted tubule of the nephron, leading to glycosuria and concomitant natriuresis [ 49 ]. In addition to its well-established effects on glucose control in patients with T2DM [ 4 , 50 ], multiple conditions have been demonstrated to be improved in patients treated with SGLT-2i agents, such as NAFLD [ 51 , 52 ], atherosclerotic cardiovascular disease [ 53 ], and chronic kidney disease [ 54 ], with a possible interaction of SGLT-2i on microbiota with cardio-renal and metabolic outcomes.…”

SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose

“…Although diabetes is detected in only a few cases in the present study, elevated fasting blood glucose was a common phenomenon at admission; however, the underlying mechanisms are yet unknown. Moreover, the effect of hypoglycemic agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, on COVID-19 remains an interesting issue worth exploration [ 30 ].…”

A Case of SGLT2 Inhibitor-Induced Euglycemic Diabetic Ketoacidosis

“…SGLT2i are a newer antidiabetic drug class that are recommended as second-line medications for type 2 diabetes mellitus as they enhance excretion and prevent reabsorption of filtered glucose molecules from the proximal renal tubules [1,2]. In recent times, their usage has significantly increased as many large trials have shown significant cardiovascular protective effects [1,3]. In recent guidelines, SGLT2i have also been incorporated as guideline-directed medical therapy for patients with heart failure [4].…”