Changes in Body Weight

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SU treatment is usually associated with weight gain, usually from 2 to 5 kg, which is problematic in a group of patients already overweight [10,11,46]. However, this effect is also commonly seen during treatment with insulin and thiazolidinediones. Compared with the latter, the increase in body weight observed at SU treatment seems to be less [9,42]. In the UKPDS, mean body weight changes ranged from 1.7 kg (glibenclamide) to 2.6 kg (chlorpropamide). Nevertheless, this undesirable effect was paralleled by maintenance of good glycaemic control as well as reduction in diabetes related (micro-)vascular complications during intensive treatment. The results of the UKPDS were confirmed by the ADOPT-study, where body weight increased by 1.6 kg in the first year, but then remained stable during glibenclamide treatment [42].

Recently developed SUs seem to have only moderate impact on weight gain or even to be neutral: In Mexican Americans treated with diet and exercise, no difference in body weight gain between glimepiride and placebo treatment was reported within 14 weeks (+2.3 vs. +2.1 kg) [47]. In another study, even body weight reduction could be observed within 12 months compared with glibenclamide [48]. Similarly, treatment with gliclazide MR seems to be at least neutral on body weight: In the GUIDE-study, body weight was stable during 27 weeks with mean changes from 83.1 to 83.6 kg and 83.7 to 84.3 kg on gliclazide MR and glimepiride, respectively [14].

Repaglinide and nateglinide seem to increase body weight only slightly or to be at least neutral. During a 1-year monotherapy study, which compared repaglinide and gliclazide, no weight gain or serious hypoglycaemic events were reported in either treatment during the study [49]. In another study, when repaglinide and nateglinide were directly compared during 16 weeks of therapy, mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group [21].

Taken together, those data suggest that the relevance of body weight gain in response to therapy with insulin secretagogues may have been overestimated even when using older SUs [9].

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