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Meta-Analysis
. 2014 Feb 12;9(2):e82880.
doi: 10.1371/journal.pone.0082880. eCollection 2014.

Safety and efficacy of gliclazide as treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials

Gijs W D Landman  1 , Geertruide H de Bock  2 , Kornelis J J van Hateren  1 , Peter R van Dijk  1 , Klaas H Groenier  3 , Rijk O B Gans  4 , Sebastiaan T Houweling  1 , Henk J G Bilo  5 , Nanne Kleefstra  1
Affiliations
Meta-Analysis

Safety and efficacy of gliclazide as treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials

Gijs W D Landman et al. PLoS One. .

Abstract

Objective and design: Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156).

Data sources: Medline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database.

Selection: Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used.

Results: Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (-0.13% (95%CI: -0.25, -0.02, I(2) 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I² 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes.

Conclusions: The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. PRISMA flow diagram.
Presentation of the procedure of literature searching and selection with numbers of articles at each stage.
Figure 2
Figure 2. Forest plot of the main effect outcome.
The main effect outcome HbA1c; gliclazide versus other glucose lowering agents. Metf = metformin, SU is sulphonylurea, Pio is pioglitazone.
See this image and copyright information in PMC

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