Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Feb 29:2020:1762164.
doi: 10.1155/2020/1762164. eCollection 2020.

SGLT2 Inhibitors, GLP-1 Agonists, and DPP-4 Inhibitors in Diabetes and Microvascular Complications: A Review

Christopher El Mouhayyar  1   2 , Ruba Riachy  2   3 , Abir Bou Khalil  2   3 , Asaad Eid  1   2 , Sami Azar  2   3
Affiliations
Review

SGLT2 Inhibitors, GLP-1 Agonists, and DPP-4 Inhibitors in Diabetes and Microvascular Complications: A Review

Christopher El Mouhayyar et al. Int J Endocrinol. .

Abstract

The prevalence of diabetes and its associated complications is increasing throughout the decades. Promising diabetes medications were introduced to the market including GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors aiming to target these complications. The literature lacks sufficient data regarding these new medications and their influence on nephropathy, retinopathy, and neuropathy. This review expands on the major results of effects of the 3 drug classes on microvascular complications. In our review, both SGLT2 inhibitors and GLP-1 agonists appear to have promising nephroprotective outcomes at this stage, with less promising outcomes seen with DPP-4 inhibitors. Moreover, the retinoprotective outcomes of both SGLT2 inhibitors and DPP-4 inhibitors were only tested on mice, while those of GLP-1 agonists were assessed in few trials. In addition, the results of both GLP-1 agonists and DPP-4 inhibitors showed discrepancies in these studies. On the contrary, conclusions regarding the effect of these medications on neuroprotective outcomes cannot be drawn at the time due to the lack of clinical trials targeting these complications. Hence, a clearer picture of the microvascular outcomes will manifest over time with the release of multiple upcoming clinical trials.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Mechanism of action of diabetes medications on multiple organ systems: (a) SGLT2 inhibitors [1]; (b) DPP-4 inhibitors [2]; (c) GLP-1 agonists [3].
See this image and copyright information in PMC

References

    1. Wanner C., Marx N. SGLT2 inhibitors: the future for treatment of type 2 diabetes mellitus and other chronic diseases. Diabetologia. 2018;61(10):2134–2139. doi: 10.1007/s00125-018-4678-z. - DOI - PubMed
    1. Mulvihill E. E., Drucker D. J. Pharmacology, Physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocrine Reviews. 2014;35(6):992–1019. doi: 10.1210/er.2014-1035. - DOI - PMC - PubMed
    1. Drucker D. J. The biology of incretin hormones. Cell Metabolism. 2006;3(3):153–165. doi: 10.1016/j.cmet.2006.01.004. - DOI - PubMed
    1. Zinman B., Wanner C., Lachin J. M., et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine. 2015;373(22):2117–2128. doi: 10.1056/nejmoa1504720. - DOI - PubMed
    1. Neal B., Perkovic V., Mahaffey K. W., et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine. 2017;377(7):644–657. doi: 10.1056/nejmoa1611925. - DOI - PubMed

LinkOut - more resources