Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

Int J Mol Sci. 2021 Mar 17;22(6):3062. doi: 10.3390/ijms22063062.

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic β-cell function and insulin sensitivity. SGLT2 inhibitors ameliorate fatty liver and reduce visceral fat mass. Furthermore, it has been noted that SGLT2 inhibitors have cardio-protective and renal protective effects in addition to their glucose-lowering effect. In addition, several kinds of SGLT2 inhibitors are used in patients with type 1 diabetes mellitus as an adjuvant therapy to insulin. Taken together, SGLT2 inhibitors have amazing multifaceted effects that are far beyond prediction like some emerging magical medicine. Thereby, SGLT2 inhibitors are very promising as relatively new anti-diabetic drugs and are being paid attention in various aspects. It is noted, however, that SGLT2 inhibitors have several side effects such as urinary tract infection or genital infection. In addition, we should bear in mind the possibility of diabetic ketoacidosis, especially when we use SGLT2 inhibitors in patients with poor insulin secretory capacity.

Keywords: cardio-protection; fatty liver; insulin resistance; pancreatic β-cells; renal protection.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / pathology
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*

Substances

  • Cardiotonic Agents
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors