A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials

Ann Med. 2012 Jun;44(4):375-93. doi: 10.3109/07853890.2011.560181. Epub 2011 Apr 15.

Abstract

Background: Current treatment of hyperglycemia in type 2 diabetes (T2DM) is often ineffective and has unwanted effects. Therefore, novel antidiabetic drugs are under development.

Objective: To assess efficacy and safety of the new antidiabetic drugs sodium glucose co-transport-2 (SGLT2) inhibitors in T2DM. Design and setting. Among 151 articles published on MEDLINE, Cochrane Library, EMBASE, PubMed, International meeting abstracts through December 2010, 13 randomized placebo-controlled trials (RCT) were included.

Measurements: Two reviewers retrieved articles and evaluated study quality by appropriate scores. Main outcomes were pooled using random- or fixed-effects models.

Results: Dapagliflozin significantly reduced HbA1c (weighted mean difference (WMD) -0.52%; 95% CI -0.46, -0.57%; P < 0.00001) fasting plasma glucose (WMD -18.28 mg/dL; 95% CI -20.66, -15.89; P < 0.00001), body mass index (WMD -1.17%; -1.41, -0.92%; P < 0.00001), systolic (WMD -4.08 mmHg; -4.91, -3.24), and diastolic (WMD -1.16 mmHg; -1.67, -0.66) blood pressure, and serum uric acid (WMD -41.50 μmol/L; -47.22, -35.79). Other SGLT2 inhibitors showed similar results. Dapagliflozin treatment increased the risk of urinary (OR 1.34; 1.05-1.71) and genital (OR 3.57; 2.59-4.93) tract infection; it also mildly increased the risk of hypoglycemia (OR 1.27; 1.05-1.53) when co-administered with insulin.

Limitations: Limitations of the literature include the small number, size, and duration of RCTs.

Conclusions: Pending confirmation from larger RCTs, this analysis shows SGLT2 inhibitors are safe and effective for hyperglycemia treatment in T2DM.

Publication types

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

MeSH terms

  • Benzhydryl Compounds / therapeutic use
  • Blood Pressure / drug effects
  • Body Mass Index
  • Canagliflozin
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Glucosides / therapeutic use
  • Glycated Hemoglobin A
  • Humans
  • Hyperglycemia / drug therapy
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transport Proteins / antagonists & inhibitors*
  • Thiophenes / therapeutic use

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sodium-Glucose Transport Proteins
  • Thiophenes
  • Canagliflozin
  • empagliflozin