Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC‐39)

Abstract

AimTo investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes.Materials and methodsWe conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged ≥18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within‐drug yearly change in body weight after receiving add‐on therapy with individual SUs during 5 years of follow‐up. The secondary outcome was within‐drug yearly change in glycated haemoglobin (HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration.ResultsA total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add‐on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after.ConclusionsIn patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add‐on therapy to metformin, without the offset of relevant weight changes.

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“…On the other hand, insulin, sulfonylurea and thiazolidine are known to induce weight gain [39]. On the contrary, it has been reported that metformin decreased body weight, and inhibited the weight gain by insulin and sulfonylurea [19,40,41]. In fact, 42.9% of the patients were prescribed insulin, sulfonylurea and thiazolidine in non-DPP-4 inhibitor group, but 30% of patients in DPP-4 inhibitor group.…”

Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus: Indian multicentric randomized trial - START Study

“…Out of the different sulfonylurea/metformin combinations studied, glimepiride/metformin combination resulted in 0.1 kg weight gain, gliclazide/metformin combination resulted in 3.9 kg weight gain, and glibenclamide/metformin combination resulted in 3.3 kg weight gain. [ 27 ] Low-dose glimepiride has also demonstrated effective plasma glucose reduction with no reports of hypoglycemia or weight gain. [ 28 ] Low-dose glimepiride, due to its peripheral insulin sensitizing effect, does not cause downregulation of the insulin receptors and thus may prevent unnecessary hyperinsulinemia and β-cell function failure.…”

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“…As a direct extension of their mechanism of action, the major adverse effect of SUs is hypoglycemia 46, 47 Weight gain is another important side effect of SUs. Many studies have demonstrated increased weight gain in patients on SUs versus metformin 47 and the UKPDS study demonstrated an increase in weight gain with SUs but even more so with insulin 17 , however not all studies have reported an increase in weight gain 48 .…”