An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials

Expert Opin Investig Drugs. 2019 Sep;28(9):811-820. doi: 10.1080/13543784.2019.1655539. Epub 2019 Aug 22.

Abstract

Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the anti-diabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2, and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated hemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis, and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.

Keywords: SGLT1; SGLT2 inhibitors; clinical trials; type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Development / methods
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors*
  • Sodium-Glucose Transporter 1 / metabolism
  • Sodium-Glucose Transporter 2 / drug effects
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • SLC5A1 protein, human
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors