Carlos Sánchez-Juan

Exenatide is a new agent, approved in 2005 and indicated for the treatment of Type 2 diabetes. It belongs to a class of drugs known as incretin mimetics. As with the endogenous incretin hormone glucagon-like peptide 1 (GLP-1), exenatide effectively lowers blood glucose levels by stimulating insulin release, inhibiting glucagon secretion and delaying gastric emptying. Nausea and vomiting are the most common adverse reactions, which lead to discontinuation in as many as 4–14% of patients in some studies (1,2). We report one patient (female; age 58 years) with exenatide-associated renal failure who presented with nausea, vomiting and reduction of blood pressure. She had Type 2 diabetes with mild chronic nephropathy [creatinine 97.2 μmol/l, creatinine clearance 65 ml/min], microalbuminuria and hypertension. Exenatide was initiated and maintained at a dosage of 5 μg twice daily. The patient had been taking stable doses of metformin, repaglinide, angiotensin-converting enzyme inhibitors and diuretics for two years. She was not using non-steroidal anti-inflammatory drugs. The time between starting exenatide therapy and diagnosis of renal failure was three months (creatinine 227.2 μmol/l; creatinine clearance 39 ml/min) and the drug was then discontinued. She did not require hospitalization. Fifteen days after withdrawal of exenatide, metformin and secretagogues, renal function had recovered (creatinine 96.3 μmol/l; creatinine clearance 68 ml/min). The tolerability and pharmacokinetics of exenatide have previously been proved and these changes were considered clinically acceptable in patients with mild renal insufficiency, and no dosage adjustment was recommended (3). Although there is no evidence that exenatide directly produces renal toxicity, from April 2005 to October 2008, the US Food and Drug Administration (FDA) received 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal impairment) in patients using exenatide (4). New cases have been reported in the last year (5). Information from the manufacturer indicates rare events of renal failure, which appears reversible with supportive treatment and discontinuation of potentially causative agents, including exenatide (4). In severe renal impairment, exenatide is contraindicated, and a careful increase in dosage should be carried out in cases of moderate renal impairment (creatinine clearance 30–50 ml/min). Exenatide will be used in people at risk of renovascular disease and the association with potentially nephrotoxic drugs (e.g. metformin, angiotensin converting enzyme inhibitors) is frequent. In addition, if exenatide therapy is associated with nausea and vomiting, the subsequent hypovolaemia may result in ischaemic renal failure. It is difficult to be certain of the role of exenatide in causing renal failure, but renal function should be monitored regularly in patients receiving exenatide, particularly those who present with nausea, vomiting or reduced fluid intake. Because these effects are frequent, a review of drug-specific information should be planned, especially concerning renal function. Nothing to declare.