A Cochrane review [Abstract] 1 included 15 studies with a total of 3781 subjects. No studies reported the effect of meglitinides on mortality or morbidity. In the eleven studies comparing meglitinides to placebo, both repaglinide and nateglinide resulted in a reductions in glycosylated haemoglobin (0.1% to 2.1% reduction in HbA1c for repaglinide; 0.2% to 0.6% for nateglinide). Repaglinide (248 participants in three trials) had a similar degree of effect in reducing glycosylated haemoglobin as metformin. Weight gain was generally greater in those treated with meglitinides compared with metformin (up to three kg in three months). Diarrhoea occurred less frequently and hypoglycaemia occurred more frequently but rarely severely enough as to require assistance.
A network meta-analysis 2 included 39 RCTs involving 17 860 individuals. Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in HbA1c compared with sulfonylureas (-0.20% ,95% CI -0.34 to -0.04%), glinides (-0.31%, 95% CI -0.61 to -0.02%), thiazolidinediones (-0.20%, 95% CI -0.38 to -0.00), α-glucosidase inhibitors (-0.36%, 95% CI -0.64 to -0.07%), and DPP-4 inhibitors (-0.32%, 95% CI -0.47 to -0.17%). HbA1c decrease was greater for biphasic insulin compared with glinides (-0.36%; 95% CI -0.82 to -0.11%). Compared with placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides, basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin.
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