Long-term Efficacy and Safety of Exenatide Treatment

We read with interest the article by Wysham et al1Wysham C.H. MacConell L.A. Maggs D.G. Zhou M. Griffin P.S. Trautmann M.E. Five-year efficacy and safety data of exenatide once weekly: long-term results from the DURATION-1 randomized clinical trial.Mayo Clin Proc. 2015; 90: 356-365Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar describing the 5-year efficacy and safety of once-weekly exenatide. Of 258 extension-phase patients, 153 (59.3%) completed 5 years of treatment in the Diabetes Therapy Utilization: Research Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) randomized clinical trial. The research determined that 2 mg of exenatide injected subcutaneously once weekly could significantly reduce hemoglobin A1c levels from baseline, and 43.9% of patients achieved hemoglobin A1c levels of less than 7.0%. Fasting plasma glucose level also significantly improved. We agree with the authors that long-term once-weekly exenatide treatment produced sustained glycemic improvement. However, the study had a high dropout rate: nearly 40% of the patients did not complete the study. The result of this study may be limited to only those patients who can tolerate the adverse effects of exenatide and not to all patients who have type 2 diabetes. Nausea, vomiting, and diarrhea are common adverse effects when patients start treatment with exenatide. High rates of patients who were lost to follow-up could bias the results. Applying intent-to-treat analysis (as employed by the authors) is also problematic when a large proportion of participants drop out. Treatment effect could be underestimated or overestimated. Moreover, intent-to-treat analysis can also hide problems related to the way in which large dropout data are handled. We strongly agree with the authors that exenatide treatment can have continued efficacy over a long period of time. However, clinical efficacy may be limited to those patients who can tolerate exenatide treatment long term. Future research that employs a randomized controlled trial design can confirm the long-term patient acceptance, clinical benefit, and safety of exenatide treatment. Five-Year Efficacy and Safety Data of Exenatide Once Weekly: Long-term Results From the DURATION-1 Randomized Clinical TrialMayo Clinic ProceedingsVol. 90Issue 3PreviewTo evaluate the 5-year efficacy and safety of once weekly exenatide. Full-Text PDF In reply—Long-term Efficacy and Safety of Exenatide TreatmentMayo Clinic ProceedingsVol. 90Issue 9PreviewWe appreciate the interest of Drs Chirapongsathorn and Anthanont in our article on the efficacy and safety of exenatide once weekly at 5 years in patients with type 2 diabetes. They appropriately point out the withdrawal rate of approximately 40% during our long-term study. We contend that this withdrawal rate is not unexpected for a clinical trial conducted over 5 years of follow-up, and, in addition, results reported at 6 years of follow-up reveal that a large proportion of patients remained in the study even longer. Full-Text PDF