Abstract
Objective and DesignGliclazide 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 SourcesMedline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database.SelectionIncluded 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.ResultsNineteen 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, I2 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.ConclusionsThe 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.
Highlights
At present, metformin is the pharmacological cornerstone for patients with type 2 diabetes (T2DM) [1]
Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs
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)
Summary
Metformin is the pharmacological cornerstone for patients with type 2 diabetes (T2DM) [1]. When metformin does not suffice or is contra-indicated, the oral treatment options are; sulphonylureas (SUs), meglitinides, a-glucosidase inhibitor, thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium glucose transporter-2 receptor (SGLT-2) inhibitors. SUs are the preferred second treatment option in for example the current NICE guidelines, whereas no specific choices have been made in the American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) position statement [1,2]. The new Dutch type 2 diabetes management guideline advises gliclazide as the preferred second treatment option and not SUs as a group. Advising gliclazide is – amongst others - based on evidence from observational studies showing cardiovascular benefits of gliclazide over other SUs [3,4,5,6,7,8]. No dose adjustments appears necessary in case of impaired renal function [15]
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