When the sulfonylureas were analyzed separately, the highest incidence of severe hypoglycemia was seen in people taking glibenclamide (13.6 per 1000 person–years) and the lowest in those on gliclazide modified release (1.66 per 1000 person–years).

Trial population Comparator treatment Links Japanese populations given lower doses Uncontrolled with lifestyle therapy and oral antidiabetic medication monotherapy Glibenclamide NCT00393718  Journal publication Uncontrolled with lifestyle therapy and oral antidiabetic medication monotherapy Investigator’s choice of oral antidiabetic medication NCT01512108 Journal publication Uncontrolled on sulfonylurea monotherapy Placebo NCT00395746 Journal publication Uncontrolled on insulin (basal/premixed/basal–bolus) Placebo NCT01572740  Journal publication Japanese populations given higher dose Uncontrolled with lifestyle therapy and oral antidiabetic medication monotherapy Liraglutide 0.9 mg NCT02505334   Chinese/Indian/Korean population given higher dose Uncontrolled on one or more antidiabetic medications Glimepiride NCT00614120 Journal publication medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Colagiuri S et al. Diabetes Res Clin Prac 2018. doi: 10.1016/j.diabres.2018.05.028

Medication availability became a larger problem for patients needing more than metformin, with glibenclamide and gliclazide only available in 75.2–84.1% of pharmacies even in high-income countries.

But maternal and infant outcomes did not otherwise differ with insulin versus oral antidiabetic agents (most commonly metformin and/or glibenclamide) across the 53 included studies, which contained data from 7381 women and 6435 infants.

So the UKPDS randomly assigned patients to receive intensive treatment with a sulfonylurea (chlorpropamide, glibenclamide, or glipizide) or insulin, or conventional treatment in the form of dietary intervention, and those who were more than 120% of their ideal bodyweight were additionally randomized to receive or not receive metformin.

Initial treatment was with sulfonylureas (then glibenclamide) for patients of a healthy weight and with metformin for those with a body mass index greater than 25 kg/m 2 .

Bowman P et al. Lancet Diabetes Endocrinol 2018. doi: 10.1016/S2213-8587(18)30106-2

Many more studies showed no increased cardiovascular risk with sulfonylurea therapy or between the different types of sulfonylurea, although Khunti noted that the risk was lowest with glicazide, followed by glimepiride and glibenclamide.