SGLT inhibitor adjunct therapy in type 1 diabetes

Diabetologia. 2018 Oct;61(10):2126-2133. doi: 10.1007/s00125-018-4671-6. Epub 2018 Aug 22.

Abstract

Non-insulin adjunct therapies in type 1 diabetes have been proposed as a means of improving glycaemic control and reducing risk of hypoglycaemia. Evidence to support this approach is, however, scant and few pharmacological agents have proved effective enough to become part of routine clinical care. Recent short-term Phase II trials and 24 week Phase III trials provide initial support for the use of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes. Two international, multicentre, randomised, controlled clinical trials, Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-1) and inTandem3, have reported that SGLT inhibition with dapagliflozin and sotagliflozin, respectively, confer additional benefits in terms of a 5-6 mmol/mol (0.4-0.5%) reduction in HbA1c accompanied by weight loss and reductions in total daily insulin doses. The reduction in HbA1c does not come with a significantly increased risk of hypoglycaemia but does carry an increased risk of diabetic ketoacidosis and mycotic infections. These results suggest that SGLT inhibition will have a place in the management of type 1 diabetes. Longer-term clinical trials (≥52 weeks) and observational cohort studies are needed to determine any additional benefits or adverse effects of this adjunct therapy and to determine which group of patients may benefit most from this approach. In addition, use of SGLT inhibitors in routine type 1 diabetes care will require specific patient and healthcare professional educational packages to ensure patient safety and to minimise risk.

Keywords: Clinical trials; Diabetic ketoacidosis; GLP-1 receptor agonist; HbA1c; Hypoglycaemia; Insulin; Review; Sodium–glucose cotransporter inhibitors; Type 1 diabetes; Weight.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Benzhydryl Compounds / pharmacology
  • Blood Glucose / drug effects
  • Body Weight
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Ketoacidosis / therapy
  • Glucosides / pharmacology
  • Glycosides / pharmacology
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • International Cooperation
  • Multicenter Studies as Topic
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors*

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycosides
  • Hypoglycemic Agents
  • SLC5A1 protein, human
  • Sodium-Glucose Transporter 1
  • dapagliflozin
  • (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol