Comparison of liraglutide versus other incretin‐related anti‐hyperglycaemic agents

Abstract

The two classes of incretin-related therapies, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have become important treatment options for patients with type 2 diabetes. Sitagliptin, saxagliptin, vildagliptin and linagliptin, the available DPP-4 inhibitors, are oral medications, whereas the GLP-1 RAs-twice-daily exenatide, once-weekly exenatide and once-daily liraglutide-are administered subcutaneously. By influencing levels of GLP-1 receptor stimulation, these medications lower plasma glucose levels in a glucose-dependent manner with low risk of hypoglycaemia, affecting postprandial plasma glucose more than most other antihyperglycaemic medications. Use of GLP-1 RAs has been shown to result in greater glycaemic improvements than DPP-4 inhibitors, probably because of higher levels of GLP-1 receptor activation. GLP-1 RAs can also produce significant weight loss and may reduce blood pressure and have beneficial effects on other cardiovascular risk factors. Although both classes are well tolerated, DPP-4 inhibitors may be associated with infections and headaches, whereas GLP-1 RAs are often associated with gastrointestinal disorders, primarily nausea. Pancreatitis has been reported with both DPP-4 inhibitors and GLP-1 RAs, but a causal relationship between use of incretin-based therapies and pancreatitis has not been established. In clinical trials, liraglutide has shown efficacy and tolerability and resulted in certain significant benefits when compared with exenatide and sitagliptin.

Diabetes-related alterations in the enteric nervous system and its microenvironment

“…Furthermore, 27% of GLP-1 receptor immunoreactive neurons in the duodenum and 79% of these neurons in the colon are co-expressed with nNOS [175] . Due to its promising potential in the treatment of type 2 diabetes and related intestinal motility disorders, the incretin-based therapies have been the focus of much interest during the last years [176][177][178][179] . Incretins, which are released by enteroendocrine cells in the intestine in response to a meal, have been implicated in contributing to the pathogenesis of type 2 diabetes mellitus.…”

Comparison of efficacy between incretin-based therapies for type 2 diabetes mellitus

“…This review examines the comparisons between two classes of incretin based therapies, dipeptidyl peptidase 4 (DPP-4) inhibitors (incretin enhancers) and glucagon-like peptide 1 (GLP-1) agonists (incretin mimetics). Although use of incretin based therapies for T2DM has been reviewed before [9-11], this article focuses on data from head to head comparative trials analyzing efficacy, tolerability and safety profiles between the agents from these two classes.…”

Non‐glycaemic effects mediated via GLP‐1 receptor agonists and the potential for exploiting these for therapeutic benefit: focus on liraglutide

“…In a substudy involving patients from the LEAD-2 and LEAD-3 studies, weight loss was found to correspond to a reduction in visceral and subcutaneous fat (as opposed to lean tissue mass), thus reducing the long-term risk of cardiovascular disease [89]. Weight loss with liraglutide is also discussed elsewhere within this supplement [23,24].The majority of GLP-1 RA-associated side effects are gastrointestinal, with most complaints relating to nausea, particularly early in treatment. Clinical data have revealed that the effect of liraglutide treatment on weight loss, which is generally a more long-term effect than the nausea, was observed irrespective of gastrointestinal adverse effects [90].…”