Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology


ISSN (Print): 2772-4328
ISSN (Online): 2772-4336


DPP4 Inhibitors: Could they be One of the Solutions for COVID-19 Patients with Prediabetes?

Author(s): Ntethelelo Hopewell Sibiya*, Bongeka Cassandra Mkhize and Andile Khathi

Volume 18, Issue 1, 2023

Published on: 06 June, 2022

Page: [88 - 91] Pages: 4

DOI: 10.2174/2772432817666220127163457


Recent reports suggest that prediabetes is a risk factor for developing severe COVID-19 complications through underlying mechanisms involving undiagnosed sub-clinical inflammation. However, we remain without a clinical approach for managing COVID-19 in prediabetic cases. The subclinical inflammation in prediabetes is associated with elevated DPP4 levels and activity. DPP4 has pleiotropic actions, including glycaemia regulation and immuno-modulation. Recently, DPP4 has been recognised as a co-receptor for COVID-19 for entering host cells. In addition to improving glycaemia, DPP4 inhibition is associated with reduced inflammation. In this submission, we explore the potential use of DPP4 inhibitors as therapeutic agents for prediabetic patients in managing the deleterious effects of COVID-19. DPP4 inhibitors (gliptins), such as linagliptin and sitagliptin, have therapeutic effects, which have been shown to extend beyond glycaemic control with no risk of hypoglycaemia. By the nature of their mechanism of action, gliptins are not associated with hypoglycaemia, unlike their anti-glycaemic counterparts, as they mainly target postprandial glycaemia. Moreover, DPP4 inhibitors may represent a safer option for prediabetic individuals in managing prediabetes either as a prophylactic or curative treatment for COVID-19. We envisage that beyond improved glycaemic control, the use of DPP4 inhibitors would also alleviate the cytokine storm, resulting in a reduction in the severity of COVID-19 symptoms and consequently reducing the morbidity and mortality in prediabetic COVID- 19 patients.

Keywords: COVID-19, prediabetes, DPP4 inhibitors, SARS-CoV2, inflammation, glycaemic control.

« Previous
Hu B, Guo H, Zhou P, et al. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 2020; 1-14.
[PMID: 33024307]
Fadini GP, Morieri ML, Longato E, et al. Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study. Diabetes Obes Metab 2020; 22(10): 1946-50.
[] [PMID: 32463179]
Sosibo AM, Khathi A. Pre-diabetes and COVID-19, could we be missing the silent killer? Exp Biol Med (Maywood) 2021; 246(4): 369-70.
[] [PMID: 33215530]
Hühn J, Ehrlich S, Fleischer B, von Bonin A. Molecular analysis of CD26-mediated signal transduction in T cells. Immunol Lett 2000; 72(2): 127-32.
[] [PMID: 10841948]
Tan CMJ, Green P, Tapoulal N, Lewandowski AJ, Leeson P, Herring N. The role of neuropeptide Y in cardiovascular health and disease. Front Physiol 2018; 9: 1281.
[] [PMID: 30283345]
Gallwitz B. Clinical use of DPP-4 inhibitors. Front Endocrinol (Lausanne) 2019; 10: 389.
[] [PMID: 31275246]
Caldeira D, Alarcão J, Vaz-Carneiro A, Costa J. Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis. BMJ 2012; 345: e4260.
[] [PMID: 22786934]
Hamming I, Timens W, Bulthuis M, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Path 2004; 203(2): 631-7.
Widagdo W, Raj VS, Schipper D, et al. Differential expression of the Middle East respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels. J Virol 2016; 90(9): 4838-42.
[] [PMID: 26889022]
Trzaskalski NA, Fadzeyeva E, Mulvihill EE. Dipeptidyl peptidase-4 at the interface between inflammation and metabolism. Clin Med Insights Endocrinol Diabetes 2020; 13: 1179551420912972.
[] [PMID: 32231442]
Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NFkappa-B pathway in-severe COVID-19 patients. Inflammopharmacology 2021; 29(1): 91-100.
Sarkar J, Nargis T, Tantia O, Ghosh S, Chakrabarti P. Increased plasma dipeptidyl peptidase-4 (DPP4) activity is an obesity-independent parameter for glycemic deregulation in type 2 diabetes patients. Front Endocrinol (Lausanne) 2019; 10: 505.
[] [PMID: 31402899]
Zheng T, Gao Y, Baskota A, Chen T, Ran X, Tian H. Increased plasma DPP4 activity is predictive of prediabetes and type 2 diabetes onset in Chinese over a four-year period: result from the China National Diabetes and Metabolic Disorders Study. J Clin Endocrinol Metab 2014; 99(11): E2330-4.
[] [PMID: 25029421]
Lee Y-S, Park M-S, Choung J-S, et al. Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes. Diabetologia 2012; 55(9): 2456-68.
[] [PMID: 22722451]
Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol (Lausanne) 2019; 10: 80.
[] [PMID: 30828317]
Nahon KJ, Doornink F, Straat ME, et al. Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes: a randomised placebo-controlled trial. Diabetologia 2018; 61(11): 2386-97.
[] [PMID: 30145664]
Pal R, Banerjee M, Mukherjee S, Bhogal RS, Kaur A, Bhadada SK. Dipeptidyl peptidase-4 inhibitor use and mortality in COVID-19 patients with diabetes mellitus: an updated systematic review and meta-analysis. Ther Adv Endocrinol Metab 2021; 12: 2042018821996482.
[] [PMID: 33680425]
Johnson JL, O’Neal KS, Pack CC, Kim MK. Management of a prediabetes case with the DPP-4 inhibitor sitagliptin. Ann Pharmacother 2014; 48(6): 811-5.
[] [PMID: 24676549]

© 2024 Bentham Science Publishers | Privacy Policy