Glucagon-Like Peptide-1 Analog and Insulin Combination Therapy in the Management of Adults with Type 2 Diabetes Mellitus

Objective: To evaluate the efficacy and tolerability of combination glucagon-like peptide-1 (GLP-1) analogs and insulin in the management of type 2 diabetes mellitus (T2DM) in adults. Data Source: A MEDLINE search (1966–April 2010) was conducted using the key terms glucagon-like peptide-1 analog, exenatide, incretin mimetic, liraglutide, diabetes mellitus, and insulin. Study Selection and Data Extraction: All English-language articles identified from the data source were evaluated and reviewed for inclusion. Original research and retrospective cohorts were included in this review. The references of articles that we identified were examined for any additional studies appropriate for review. Data Synthesis: Exenatide is a subcutaneously administered GLP-1 receptor agonist that is used for the improvement of glycemic control in adults with T2DM. Through actions similar to those of endogenous GLP-1, exenatide contributes to improved postprandial glycemic control and weight loss. The concomitant use of exenatide and insulin is currently not Food and Drug Administration-approved due to lack of clinical trial data. However, combination insulin and exenatide may be advantageous, especially for reducing weight gain, particularly for obese patients with T2DM. Several small prospective and retrospective studies evaluating combination therapy found statistically significant reductions in hemoglobin A1c (A1C), weight, and total daily insulin dose requirements. The most common adverse effects reported included gastrointestinal effects, such as nausea and vomiting, and hypoglycemia. Conclusions: Although there is a limited amount of data and not all studies demonstrated A1C reduction, the combination of exenatide with insulin therapy appears to be a safe option in the management of T2DM. It may be a promising therapeutic strategy for some patients, as reductions in weight and insulin doses were observed. Further well-designed prospective trials are warranted to fully determine the long-term effectiveness and safety of this combination as well as its place in therapy.