Safety and Efficacy of Gliclazide as Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Trials

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.

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

“…25,26 A meta-analysis of SU trials concluded that severe hypoglycaemia was rare with gliclazide, especially if the dose does not exceed 240 mg daily. Non-severe hypoglycaemia was seen mainly in those on 320 mg daily.…”

Effects of sulfonylurea treatment on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus: A network meta-analysis

“…Reduced TNF-α and elevated adiponectin levels correlate with improved insulin resistance, which is thought to be associated with low blood PAI-1 levels [34,35]. Furthermore, glibenclamide and glimepiride carry a higher risk of hypoglycemia thangliclazide [36]. Low blood glucose levels increase blood PAI-1 levels [37], which may beanother reason why blood PAI-1 levels are lower after using gliclazide than after using glimepiride.…”

Within-class differences of the sulfonylureas should be accounted for

“…One of the other main advantages of gliclazide is its safety in severe renal failure [5]. In addition, two metaanalyses have reported that of all the sulfonylureas, gliclazide is associated with the lowest risk of hypoglycaemia [6]. For example, the hypoglycaemic event rate for gliclazide is 50% lower than that for glimepiride [7] and is comparable to that for dipeptidyl peptidase-4 inhibitors [8,9].…”