Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials

Diabetes Obes Metab. 2014 May;16(5):457-66. doi: 10.1111/dom.12244. Epub 2013 Dec 29.

Abstract

Aims: Sodium glucose co-transport-2 (SGLT-2) inhibitors, a new class of glucose-lowering agents, reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. The aim of the present meta-analysis is the assessment of the overall efficacy and safety profile of these drugs.

Methods: A meta-analysis was performed including all trials with a duration of at least 12 weeks, comparing a SGLT-2 inhibitor with a non-SGLT-2 inhibitor agent in type 2 diabetes. The principal outcome of this analysis was the effect of SGLT-2 inhibitors on HbA1c at 12, 24 and 52 weeks. Hypoglycaemia, genital and urinary infections were retrieved and combined to calculate Mantel-Haenszel odds ratio (MH-OR). Furthermore, data on body mass index (BMI), endpoint fasting plasma glucose, systolic and diastolic blood pressure, creatinine, hematocrit and lipid profile were collected.

Results: Among placebo-controlled trials, HbA1c reduction at 12, 24 and 52 weeks was 0.5 [0.4; 0.6], 0.6 [0.6; 0.5] and 0.6 [0.7; 0.5]%. In placebo-controlled studies, 24-week reduction of HbA1c with SGLT-2 inhibitors was greater in trials enrolling patients with a lower mean age and duration of diabetes, and a higher baseline BMI, HbA1c and fasting glucose. In placebo-controlled trials, SGLT-2 inhibitors determined a weight loss during the first 24 weeks, which was maintained up to 52 weeks.

Conclusions: SGLT-2 inhibitors are effective in the treatment of type 2 diabetes, providing additional benefits, such as weight loss, reduction of blood pressure and increase in high-density lipoprotein (HDL)-cholesterol. Apart from genital and urinary infections, rather frequent but usually mild, SGLT-2 inhibitors appear to be well tolerated.

Keywords: SGLT-2 inhibitor; meta-analysis.

Publication types

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

MeSH terms

  • Benzhydryl Compounds / administration & dosage*
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Genital Diseases, Female / chemically induced
  • Genital Diseases, Male / chemically induced
  • Glucosides / administration & dosage*
  • Glycated Hemoglobin A / drug effects*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transport Proteins / antagonists & inhibitors*
  • Treatment Outcome
  • Urinary Tract Infections / chemically induced

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sodium-Glucose Transport Proteins
  • hemoglobin A1c protein, human