Symposium: III Reunión Cientifica TerapeuticaOndansetron and Metformin-Induced Gastrointestinal Side EffectsHoffmann, Irene S.1; Roa, Magaly1; Torrico, Fatima1; Cubeddu, Luigi X. * Author Information 1Center for the Detection and Treatment of Silent Cardiovascular Risk Factors (SIL-DETECT), Clinical Pharmacology Unit, Central University of Venezuela, Caracas, Venezuela; 2Nova Southeastern University, Department of Pharmaceutical Sciences, HPD, Fort Lauderdale, Florida (Dr Cubeddu). *Address for correspondence: Nova Southeastern University, Department of Pharmaceutical Sciences, HPD, 3200 South University Drive, Fort Lauderdale, FL 33328. E-mail: [email protected] This study was supported by grants from the Consejo Nacional de Investigaciones Cientificas y Tecnologicas, CONICIT SI-96001890 and from The Consejo de Desarrolo Cientifico y Humanistico de la Universidad Central de Venezuela, CDCH 06-10.4214.98, CDCH 06.30.4362.99. American Journal of Therapeutics: November 2003 - Volume 10 - Issue 6 - p 447-451 Buy Abstract Treatment with metformin is associated with a high incidence of gastrointestinal side effects of unknown mechanism. Metformin is a biguanide derivative, which resembles 5-HT3–receptor agonists in its structure. Activation of 5-HT3 receptors is known to induce nausea, vomiting, and diarrhea. In this study, we investigated if the gastrointestinal side effects produced by metformin were antagonized by ondansetron, a selective antagonist of 5-HT3 receptors. Patients experiencing gastrointestinal side effects were randomized to ondansetron (4 mg bid po) or placebo while maintained on metformin (double-blind, parallel-group design). If side effects persisted or worsened, metformin was discontinued and the patient considered a therapeutic failure. Of the 98 subjects treated with metformin, 22 developed side effects to match the study entry criteria. Diarrhea was the most frequent side effect. Subjects were randomized to ondansetron (10/2 F/M, 42.8 ± 2.3 years, 28.6 ± 1.1 kg/m2, 2585 ± 35 mg/d metformin) or placebo (9/1 F/M, 43 ± 4.3 years, 29.7 ± 1.8 kg/m2, 2715 ± 71 mg/d metformin). Ondansetron showed no efficacy against metformin-induced side effects. A comparable number of therapeutic failures were observed in ondansetron (8/12; 66%) and placebo-treated subjects (5/10; 50%) (P < 0.1). Mean nausea scores (numeric analog scale) before and during treatment with ondansetron were 6.3 ± 1 and 6.9 ± 1 cm, respectively. Nausea scores averaged 7.3 ± 1.5 and 5.9 ± 1.5cm, before and during treatment with placebo (P > 0.1). In conclusion, 5-HT3 receptors do not seem to play a role in metformin-induced gastrointestinal side effects. © 2003 Lippincott Williams & Wilkins, Inc.