Endocrinol Metab.  2017 Sep;32(3):316-325. 10.3803/EnM.2017.32.3.316.

Effects of Incretin-Based Therapies on Diabetic Microvascular Complications

• Kang YM
• Jung CH

• KMID: 2389811
• DOI: http://doi.org/10.3803/EnM.2017.32.3.316

Abstract

The morbidity and mortality associated with diabetic complications impose a huge socioeconomic burden worldwide. Therefore, the ultimate goal of managing diabetes mellitus (DM) is to lower the risk of macrovascular complications and highly morbid microvascular complications such as diabetic nephropathy (DN) and diabetic retinopathy (DR). Potential benefits of incretin-based therapies such as glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on the diabetic macrovascular complications have been recently suggested, owing to their pleiotropic effects on multiple organ systems. However, studies primarily investigating the role of these therapies in diabetic microvascular complications are rare. Nevertheless, preclinical and limited clinical data suggest the potential protective effect of incretin-based agents against DN and DR via their anti-inflammatory, antioxidative, and antiapoptotic properties. Evidence also suggests that these incretin-dependent and independent beneficial effects are not necessarily associated with the glucose-lowering properties of GLP-1 RAs and DPP-4 inhibitors. Hence, in this review, we revisit the preclinical and clinical evidence of incretin-based therapy for DR and DN, the two most common, morbid complications in individuals with DM. In addition, the review discusses a few recent studies raising concerns of aggravating DR with the use of incretin-based therapies.

Keyword

Glucagon-like peptide 1; Dipeptidyl-peptidase IV inhibitors; Diabetic microvascular complications; Effect; Retinopathy; Nephropathy

MeSH Terms

Diabetes Complications
Diabetes Mellitus
Diabetic Nephropathies
Diabetic Retinopathy
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1
Mortality
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1

Figure

• 

  Fig. 1 Schematic representation of the pleiotropic effect of incretin-based drugs with respect to chronic diabetic vascular complications. Modified from Aroor et al. [4], with permission from American Physiological Society. GLP-1 RA, glucagon-like peptide-1 receptor agonist; GLP-1R, glucagon-like peptide-1 receptor; GIP, gastric inhibitory peptide; AGE, advanced glycation end product; DPP-4, dipeptidyl peptidase-4; SDF-1α, stromal cell-derived factor 1α; EPC, endothelial progenitor cell; BNP, brain natriuretic peptide; NPY-1, neuropeptide Y-1; IL, interleukin.

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