Add A Thiazolidinedione Or Exenatide To Orals?

The introduction of several new therapeutic agents for the treatment of type 2 diabetes has led to significant challenges for providers in deciding which agent to select during the disease course.

Studies were examined to provide a relative comparison of the efficacy and safety of adding thiazolidinediones (TZDs) or exenatide to oral agents for the management of type 2 diabetes.

Studies in PubMed, MEDLINE, CINHAL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, EMBASE (inception to March 2008 for all databases), and abstracts presented at the 2006 and 2007 American Diabetes Association conferences were reviewed.

Studies were included in the analysis if they (1) were published in English, (2) were prospective, randomized, and controlled with placebo or comparator, (3) were at least 24 weeks' duration, (4) included nonpregnant adults with type 2 diabetes, (5) were full-text, peer-reviewed articles examining the efficacy of either TZDs (rosiglitazone or pioglitazone) or exenatide in combination with other oral drugs, and (6) included hemoglobin A(1C) (AIC) outcomes in a manner that allowed data analysis.
The mean change in A1c levels were evaluated along with  proportion of subjects reaching A1C goals of less than 7%, mean change in fasting plasma glucose (FPG) and body weight, and the occurrence of nonsevere hypoglycemia and gastrointestinal adverse events, were also evaluated.

The results from a total of 5212 TZD and 3582 exenatide publications were identified. After critical evaluation, 22 publications met all of the inclusion criteria for the meta-analysis. A1C was reduced from baseline for TZDs (weighted mean difference -0.80%; 95% CI -1.10 to -0.50) and exenatide (weighted mean difference -0.60%; 95% CI -1.04 to -0.16). Compared with controls, TZD- and exenatide-based therapies had odds ratios greater than 1 for reaching A1C targets of less than 7%.
FPG concentrations were reduced significantly from baseline in the TZD-based regimens, but did not achieve significance in the exenatide trials  Body weight was reduced with exenatide and increased in subgroup analyses for TZDs.  There was no significant association between TZD or exenatide therapy and the risk of nonsevere hypoglycemia. The odds ratios for nausea, vomiting, and diarrhea with exenatide relative to controls were 9.02, 4.56, and 2.96, respectively.

From the results it was concluded that  TZDs and exenatide have modest but beneficial effects on glycemic control and are relatively safe in regard to the adverse events studied. TZDs produce greater improvement in glycemic control, while exenatide is associated with reduction in body weight.

Ann Pharmacother. 2008 Nov;42(11):1541-51. Epub 2008 Oct 28.