Incretin-Based Therapies: Focus on Effects Beyond Glycemic Control Alone

Abstract

Type 2 diabetes is associated with a high prevalence of comorbidities resulting from hypertension, dyslipidemia, and hyperglycemia. Inadequate management of these risk factors will eventually result in detrimental health consequences. Thus, the effect of a drug on factors such as weight, cardiovascular (CV) risk factors, and adherence is important to consider. A review was undertaken of the recent medical literature describing the extraglycemic characteristics of the two classes of incretin-based therapies—glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors. PubMed searches were performed to identify published data on incretin therapies that describe their effects on CV risk factors, CV events, and factors related to medication adherence. The maintenance or loss of weight associated with the use of GLP-1RAs and DPP-4 inhibitors is well described in the medical literature. These agents also appear to be associated with a modest decrease in blood pressure and a reduced risk of CV events. In addition, several characteristics of incretin therapies may improve rates of medication adherence, such as generally favorable tolerability profiles (particularly with DPP-4 inhibitors), the availability of formulations that simplify treatment regimens, and a low risk for hypoglycemia. The literature on incretin therapies describes a number of clinical characteristics that are relevant to the management of extraglycemic risk factors. As part of a holistic treatment strategy, these properties constitute important considerations for tailoring therapy to individual patients with type 2 diabetes.

Impact of dipeptidyl peptidase-4 inhibitors on serum adiponectin: a meta-analysis

“…Incretin-based therapies, GLP-1 agonists, and DPP4 inhibitors offer optimal glucose-lowering effect without increasing the risk for hypoglycemia and weight gain [41]. Exendin-4, which is a GLP-1R agonist, upregulates adiponectin mRNA and increases secretion of adiponectin via a protein kinase A pathway [42].…”

Roflumilast: a review of its use in the treatment of COPD

“… 54 Glucagon-like peptide-1 receptor agonists are used in the treatment of diabetes and are also associated with weight loss. 55 This may serve as another possible explanation for the weight loss seen in patients with COPD treated with roflumilast and could also explain favorable effects on glycemic parameters as well as the gastrointestinal AEs (nausea and diarrhea) associated with the drug. In a 12-week, placebo-controlled trial in patients with newly diagnosed type 2 diabetes mellitus, roflumilast increased insulin sensitivity and was associated with a significantly greater change in glycated hemoglobin than placebo (least-square mean =−0.45%; P <0.0001) ( Figure 4 ).…”

A pilot three-month sitagliptin treatment increases serum adiponectin level in Japanese patients with type 2 diabetes mellitus- a randomized controlled trial START-J study

“…Incretin-based therapies, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, enhance the glucose-dependent insulin secretion and optimize the management of glycemic control without hypoglycemia and weight gain [ 26 ]. DPP-4 inhibitors were clinically introduced in 2006, with sitagliptin (Glactiv®, Januvia®, Xelevia™, Tesavel®) as the first agent [ 27 ], followed by vildagliptin, saxagliptin, linagliptin, teneligliptin, alogliptin, and anagliptin.…”