The treatment of type 2 diabetes mellitus (T2DM) has included the use of metformin and sulfonylurea (SU) as first-line anti-diabetic therapies world over since years. This remains, despite the knowledge that the combination results in a progressive decline in [beta]-cell function and by 3 years up to 50% of diabetic patients can require an additional pharmacological agent to maintain the glycosylated hemoglobin (HbA1c) <7.0% (UKPDS). Gliptins represent a novel class of agents that improve beta cell health and suppress glucagon, resulting in improved post-prandial and fasting hyperglycemia. They function by augmenting the incretin system (GLP-1 and GIP) preventing their metabolism by dipeptidyl peptidase-4 (DPP-4). Not only are they efficacious but also safe (weight neutral) and do not cause significant hypoglycemia, making it a unique class of drugs. This review focuses on gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin) discussing pharmacokinetics, pharmacodynamics, efficacy, and safety.
The treatment of type 2 diabetes mellitus (T2DM) has included the use of metformin (particularly in the overweight patient) and sulfonyurea (SU) (in both lean and overweight patient), as first line anti-diabetic therapies world over. Prior to 1995, the use of SU was the most popular anti-diabetic therapy in the USA (United States). SU's act by increasing insulin secretion in a glucose-independent manner, thereby risking severe unpredictable hypoglycemia, particularly if the meal is delayed or if its carbohydrate quantity reduced. The use of metformin only became popular in the US post 1995.
It only makes sense that they continue to remain mainstay therapy as despite their problems they are best suited to deal with the original pathogenic triumvirate theory for T2DM proposed by Ralf Defranzo, (qualitative and quantitative beta cell failure and insulin resistance at level of liver and peripheral tissue). This was particularly true since there was no agent that could help improve health of the beta cell and cause insulin release in a glucose dependant manner. This all changed once it was learnt that the incretin system was involved in the pathogenesis of T2DM. Failure of this incretin system has been implicated in progression of beta-cell failure and therefore any therapy that can augment this system has been shown to promote beta cell health and insulin release in a glucose-dependent manner.
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Indian J Endocrinol Metab. 2011 Oct-Dec; 15(4): 298â€“308. Choosing a Gliptin, Vishal Gupta and Sanjay Kalra1, Department of Endocrinology, Jaslok Hospital and Research Centre, 15 Deshmukh Marg, Mumbai 400026, India
1Bharti Hospital and BRIDE, Karnal, India; Corresponding Author: Dr. Vishal Gupta, Department of Endocrinology, Jaslok Hospital and Research Centre, 15 Deshmukh Marg, Mumbai 400 026, India. E-mail:email@example.com