TY - JOUR
T1 - Safety and Efficacy of Gliclazide as Treatment for Type 2 Diabetes
T2 - A Systematic Review and Meta-Analysis of Randomized Trials
AU - Landman, Gijs W D
AU - de Bock, Geertruide H
AU - van Hateren, Kornelis J J
AU - van Dijk, Peter R
AU - Groenier, Klaas H
AU - Gans, Rijk O B
AU - Houweling, Sebastiaan T
AU - Bilo, Henk J G
AU - Kleefstra, Nanne
PY - 2014/2/12
Y1 - 2014/2/12
N2 - 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, I-2 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.
AB - 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, I-2 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.
KW - MEDICAL JOURNAL EDITORS
KW - INSULIN SECRETAGOGUES
KW - INTERNATIONAL COMMITTEE
KW - MYOCARDIAL-INFARCTION
KW - POTASSIUM CHANNELS
KW - GLYCEMIC CONTROL
KW - DOUBLE-BLIND
KW - METFORMIN
KW - PIOGLITAZONE
KW - COMBINATION
U2 - 10.1371/journal.pone.0082880
DO - 10.1371/journal.pone.0082880
M3 - Review article
C2 - 24533045
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e82880
ER -