Comparative evaluation of incretin-based antidiabetic medications and alternative therapies to be added to metformin in the case of monotherapy failure

Aims/Introduction: To compare clinical consequences of using inretin-based medications versus conventional antidiabetic agents as add-on to metformin in case of monotherapy failure in patients with type 2 diabetes. Materials and Methods: The medical literature including recent abstracts from international diabetes conferences was searched for reports from clinical trials with incretin mimetics (GLP-1 receptor agonists), inhibitors of dipeptidyl peptidase-4 (DPP-4, incretin enhancers) and conventional antidiabtic drugs coadministered with metformin after monotherapy failure. A scoring system is suggested to compare the clinical utility of using incretin-based versus conventional antidiabetic agents in this situation. Results: Incretin mimetics and DPP-4 inhibitors on top of metformin treatment help achieve glycaemic control comparable to other efficient antidiabetic drugs, both if separate or head-to-head trials were considered. Incretin-based antidiabetic drugs did not cause hypoglycaemia (different from sulfonylureas, meglitinides and insulin) and weight gain (different from sulfonylureas, meglitinides, thiazolidinediones, and insulin). DPP-4 inhibitors were weight neutral, incretin mimetics lead to weight loss. The clinical profile of incretin-based medications received the highest scores, followed by alpha-glucosidase inhibitors, with far lower scores assigned to insulin, glitazones, and sulfonyureas (in this order). Conclusions: Based on the results from clinical trials, incretin-based medications have been shown to be efficacious antidiabetic drugs with a favourable adverse event and tolerability profile. This leads to high scores using a novel system paying attention to multiple facets contributing to the selection of antidiabetic drugs for general recommendation and individual treatment choices. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00004.x, 2010)