Abstract
Type 2 diabetes mellitus is widely prevalent and is often coexistent with obesity. Many of the available treatment options have side effects such as weight gain which often affect patient's willingness to continue the treatment. Effective weight loss, lack of significant hypoglycaemia, and favourable cardiometabolic profile make Incretin based therapies an attractive treatment option for type 2 diabetes. Incretin based therapies are available as either incretin mimetics (also called GLP-1 agonists) or incretin enhancers (DPP-4 inhibitors). Although agents in both these classes of incretin based therapy are effective through a common GLP-1 pathway, there are many differences amongst them including the route of administration, frequency of administration, effects on body weight, extent of glycaemic improvement. There are several trials evaluating these individual incretin based agents either as monotherapy or in combination with other anti-diabetic agents, however very few have looked into direct comparison amongst the agents in these two classes. This review is aimed to look at important mechanistic differences between incretin mimetics and enhancers through direct comparison trials and impact of these differences on biochemical, metabolic and patient satisfaction parameters.
Highlights
The prevalence of type-2 diabetes mellitus (T2DM) is rapidly increasing worldwide
This review examines the comparisons between two classes of incretin based therapies, dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists
Gastrointestinal side effects As noticed in short term mechanistic studies, all the longer term comparative randomized controlled trial (RCT) showed more initial nausea and vomiting with GLP-1 agonists compared to DPP-4 inhibitors
Summary
The prevalence of type-2 diabetes mellitus (T2DM) is rapidly increasing worldwide. The International Diabetes Federation (IDF) estimates the current prevalence of diabetes at around 366 million which is estimated to increase to 552 million cases of diabetes and 398 million cases of impaired glucose tolerance (IGT) by 2030 [1]. The effect of differential calorie intake and the reduced gastric emptying noticed during short term mechanistic studies between agents in the GLP-1 analogue and DPP4 inhibitors groups probably explain the differential weight loss in favor of GLP-1 agonists in the subsequent longer term head to head comparisons up to a one-year period. Data from long term studies, such as the 1860-Lira-DPP-4 trial, have not shown any increase in the mean calcitonin level, which is the marker of C cell hyperplasia and medullary thyroid carcinoma, in patients treated with liraglutide [33,59]. In the double blind placebo controlled DURATION 4 trial there was no significant difference in weight-related quality of life, binge-eating behavior or health status between exenatide QW and sitagliptin monotherapy
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