Orlistat Metformin

Orlistat improved glycaemic control, which resulted in the need to reduce the dose of glibenclamide (glyburide) or glipizide in almost half the patients in one study. In other studies, orlistat also reduced the dose requirement for metformin and for insulin. Orlistat did not alter the pharmacokinetics of glibenclamide or metformin. Orlistat and cimetidine may have contributed to a case of metformin-associated lactic acidosis. The manufacturers recom-... 

Diabetic patients Weight-loss induction by orlistat may be accompanied by improved metabolic control in diabetic patients, which might require a reduction in dose of oral hypoglycemic medication (eg, sulfonylureas, metformin) or insulin. Misuse potential As with any weight-loss agent, the potential exists for misuse of orlistat in inappropriate patient populations (eg, patients with anorexia nervosa or bulimia). 

A possible interaction of orlistat with metformin has been reported. 

A 59-year-old obese woman with normal renal function, taking metformin 500 mg tds, took orlistat 120 mg tds for 3 months (147). She developed abdominal pain and diarrhea, for which she was given cimetidine, and became weak and dizzy, with blurred vision, reduced consciousness, agitation, and confusion. Her pH was 6.5, bicarbonate 2 mmol/1, base deficit 38 mmol/1, and lactate 21 mmol/1. She required rehydration, bicarbonate, inotropic support and renal replacement therapy. 

The authors suggested that chronic diarrhea induced by orlistat could have led to impaired renal function or that orlistat could have increased the absorption of metformin by reducing fat absorption. 

Dawson D, Conlon C. Case study metformin associated lactic acidosis could orlistat be relevant Diabetes Care 2003 26 2471-2. 

Miles, J. M., L. Leiter, P. Hollander, T. Wadden, J. W. Anderson, M. Doyle, et al. (2002). Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care 25(7) 1123-8. 

Beneficial results in the glycemic profile (mean reduction of fasting glucose by about 0.8 mmol/L) have been reported with orlistat-induced weight loss in 6- to 12-month studies in obese type 2 diabetic patients. This has been found also when orlistat was given as an adjunct to antidiabetic treatment such as with metformin and sulphonylurea drugs. Smaller but significant reductions of HbAlc have also been found by orlistat treatment (placebo controlled). 

Cimetidine 800 mg daily was found to reduce the renal clearance of metformin in 7 healthy subjects by 27% and increase the AUC by 50%. A 59-year-old woman with type 2 diabetes taking long-term metformin 500 mg three times daily developed severe metabolic acidosis with cardiovascular collapse and acute renal failure. Three months previously she had started orlistat 120 mg three times daily, which caused chronic diarrhoea. During the 4 days before hospital admission, she was prescribed cimetidine 400 mg twice daily for her abdominal pain. The metformin-assoeiated lactic acidosis was considered to have been precipitated by the orlistat , (p.498) and cimetidine. ... 

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