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

• Published in: Diabetes & metabolism 2008-02, Vol.34, p.S78-S90
• Main Authors: Penfornis, A, Borot, S, Raccah, D
• Format: Article
• Language: English
• Subjects: Administration, Oral; Agonistes du GLP-1; Clinical Trials as Topic; Diabetes Mellitus, Type 2 - drug therapy; Diabète de type 2; DPP-4 inhibitors; Endocrinology & Metabolism; GLP-1 agonists; Glucagon-Like Peptide 1 - agonists; Glucagon-Like Peptide 1 - physiology; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Incretin-based agents; Inhibiteurs du DPP-4; Internal Medicine; Metformin - therapeutic use; Médicaments de l’effet incrétine; Placebos; Stratégie thérapeutique; Sulfonylurea Compounds - administration & dosage; Sulfonylurea Compounds - therapeutic use; Thiazolidinediones - administration & dosage; Thiazolidinediones - therapeutic use; Treatment strategy; Type 2 diabetes mellitus
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/S1262-3636(08)73399-8

Abstract 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 HbA1c (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 HbA1c (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 HbA1c 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 β-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.