A meta-analysis of the hypoglycaemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes

Diabetes Obes Metab. 2014 Sep;16(9):833-40. doi: 10.1111/dom.12287. Epub 2014 Apr 10.

Abstract

Aim: To assess hypoglycaemic risk with sulphonylureas in comparison with other drugs in randomized controlled trials.

Methods: Randomized trials with a duration ≥ 24 weeks, enrolling patients with type 2 diabetes, comparing sulphonylureas with placebo or active drugs different from other sulphonylureas. The principal outcome was the effect of sulphonylureas on the incidence of any or severe hypoglycaemia. Cumulative incidence of hypoglycaemia was estimated combining sulphonylurea groups of different trials with a random effect model and used for meta-regression analyses.

Results: The incidence of severe hypoglycaemia in patients treated with sulphonylureas was 1.2 [1.0-1.6]%. The overall risk of severe hypoglycaemia was increased more than threefold with sulphonylureas than with comparators. The proportion of patients with at least one hypoglycaemia while on sulphonylureas was 17.4 [14.5-20.8]%. The overall risk (Mantel-Haenszel Odds Ratio) of any hypoglycaemia with sulphonylureas versus comparators was 3.69 [3.47-3.93] (p < 0.001). Meta-regression analysis suggested that the incidence of any hypoglycaemia was higher in trials enrolling patients with higher body mass index (BMI) and lower haemoglobin A1c (HbA1c).

Conclusions: In conclusion, hypoglycaemia, including severe hypoglycaemia, is frequent in patients treated with sulphonylureas, particularly when baseline HbA1c levels are lower and BMI levels higher. Further studies are needed to characterize predictors for the identification of patients at higher risk.

Keywords: meta-analysis; sulphonylureas.

Publication types

  • Meta-Analysis

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Incidence
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / adverse effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human