Characterization and clinical management of clozapine-induced fever.

OBJECTIVE: To characterize clozapine-induced fever and suggest clinically relevant management recommendations. DATA SOURCES: Literature was accessed through MEDLINE (1966-June 2007) using the terms clozapine, fever, and adverse effects. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles about human studies of fever associated with the use of clozapine were evaluated. DATA SYNTHESIS: Mild to high-grade fever frequently accompanies clozapine therapy. Fever usually occurs within 10-15 days after treatment initiation and has been reported to last between 2 and 4 days. The mechanism and clinical implications of clozapine-induced fever are unclear. The primary concern for clinicians, with regard to these fevers, is the possibility of 2 serious conditions: agranulocytosis with infection or neuroleptic malignant syndrome (NMS). However, the presence of fever during clozapine therapy does not appear to predict agranulocytosis, NMS, or an increased rate of drug discontinuation at 1 year. CONCLUSIONS: Available data suggest that clozapine-induced fevers are benign; once infectious and other medical causes for fever are ruled out, clozapine therapy can be continued.

Incretin mimetics as emerging treatments for type 2 diabetes.

OBJECTIVE: To review the physiology, pharmacology, and clinical efficacy of glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide in clinical studies. DATA SOURCES: Primary literature obtained via MEDLINE (1966-April 2004) and International Pharmaceutical Abstracts (1970-April 2004) searches; abstracts obtained from meeting sources and manufacturers. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with type 2 diabetes were reviewed. Data from animal studies were also included if human data were not available. Primary and review articles related to the physiology, development, and evaluation of GLP-1s were reviewed. DATA SYNTHESIS: GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin mimetics that have been shown in human studies to be an effective treatment to improve glycemic control in patients with type 2 diabetes. Mechanisms by which these compounds improve glycemic control include enhancing glucose-dependent pancreatic secretion of insulin in response to nutrient intake, inhibiting glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1 has been shown to promote pancreatic progenitor cell differentiation and improve beta-cell function and lifespan. Reported adverse effects of exenatide and liraglutide include nausea, vomiting, and transient headache, as well as increased risk of hypoglycemia when used with sulfonylureas. CONCLUSIONS: Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic control for patients with type 2 diabetes through unique mechanisms not available with current pharmaceutical products. Ongoing Phase III studies will help to further position these compounds as treatment options for patients with type 2 diabetes.