Erythromycin improves glycaemic control in patients with Type II diabetes mellitus

Aims/hypothesis. Erythromycin mimics the effect of the gastrointestinal hor mone motilin by binding to its receptor and acting as a motilin agonist. We recently found that motilin stimulates insulin secretion at lower doses th an doses required to stimulate gastric contractile activity. We studied the effects of erythromycin on insulin secretion and glycaemic control in pati ents with diabetes mellitus. Methods. Inpatients (n = 34) with Type II (non-insulin-dependent) diabetes mellitus were randomly assigned to receive either erythromycin (400 mg oral ly three times a day, n = 19) or a placebo (n = 15) for 1 week (first study ). Another 34 outpatients with Type II diabetes were also treated with eryt hromycin (200 mg orally three times a day, n = 17) or a placebo (n = 17) fo r 4 weeks (second study). Finally, nine inpatients with Type II diabetes an d eight normal control subjects received intravenous erythromycin (10 mg.kg (-1).h(-1)) or saline infusion and insulin secretion was examined (third st udy). Results. Erythromycin lowered fasting blood glucose and fructosamine concen trations (p < 0.01) and increased basal as well as glucose-stimulated insul in secretion (p<0.05-0.01) (first study). Low doses of erythromycin treatme nt for 4 weeks also significantly improved glycaemic control in Type II dia betic patients (second study). Erythromycin infusion significantly increase d plasma insulin and decreased glucose concentrations in Type II diabetic a nd control subjects and greatly potentiated glucose-induced insulin secreti on in the latter (third study). Conclusion/interpretation. These results indicate that erythromycin given o rally has an antidiabetogenic effect and therefore erythromycin derivatives that lack the antibacterial activity could have a therapeutic value in Typ e II diabetic patients.