Therapeutic approach of type 2 diabetes mellitus with GLP-1 based therapies.

The goal of this review is to think about how to incorporate the GLP-1 based agents, represented by the dipeptidyl peptidase-4 (DPP-4) inhibitors or the glucagon-like peptide-1 (GLP-1) analogs, in the guidelines for the management of type 2 diabetes (T2DM). Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA(1c) (absolute values) by 0.5-1.1% (5 to 12%, relative values), with few adverse events and no weight gain. The sub-cutaneous injected GLP-1 analogs show larger reductions in HbA(1c) (0.8-1.7%, absolute values; 9.4-20.0%, relative values), associated with weight loss (1.75-3.8 kg); their most common adverse events are gastrointestinal symptoms which contribute to a substantial treatment interruption. If they do not challenge the use of metformin as the initial therapy of T2DM, several studies argue in favour of the use of DPP-4 inhibitors, either in combination with metformin as the initial treatment or, in add-on therapy to metformin. The advantages of this combination over others currently used are reviewed. In patients not tolerating metformin, DPP-4 inhibitors seem to be an excellent alternative as a monotherapy. As long as oral triple therapy is concerned, the choice for the association metformin + thiazolidinedione + incretin-based drug, has again several theoretical advantages against other triple therapy combinations. Finally, in patients with T2DM inadequately controlled with maximal tolerated oral multi-therapies, GLP-1 agonists are a good alternative to insulin therapy, allowing reaching a better glycaemic control together with a weight loss. However, for patients who do not tolerate GLP-1 agonist treatment, and for those not reaching the HbA(1c) target, insulin will remain necessary, allowing getting a better metabolic control, with few adverse events. The long-term effect of these new agents on glycaemic control has not yet been established, and their potential impact on beta-cell function in humans remains an area of active investigation. So, further studies are needed and will allow progressively refining the use of incretin-based agents in T2DM treatment strategy.