Anti-inflammatory properties of antidiabetic drugs: a “promised land” in the COVID-19 era?

Katsiki, Niki; Ferrannini, Ele

doi:10.1016/j.jdiacomp.2020.107723

Cited by 91Diabetes Treatment and ManagementCOVID-19 Clinical Research StudiesAdipokines, Inflammation, and Metabolic Diseases

Anti-inflammatory properties of antidiabetic drugs: a “promised land” in the COVID-19 era?

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Katsiki, Niki, Ferrannini, Ele·2020·Journal of Diabetes and its Complications

DOI 10.1016/j.jdiacomp.2020.107723PMC PMC7448766

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Abstract

Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers [i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin] were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic. Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.

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Decreases in hsCRP have also been observed with other classes of antihyperglycemic drug (metformin, DPP-4 inhibitors, and SGLT-2 inhibitors), but with less consistency than with GLP-1RAs.
“Decreases in hsCRP have also been observed with other classes of antihyperglycemic drug (metformin, dipeptidyl peptidase-4 inhibitors, and SGLT-2 inhibitors), but with less consistency than with GLP-1RAs [27].”
From Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials (2022) · cites this paper as [27]
The Sitagliptin and SGLT2-inhibitor sections report both hsCRP decreases and studies with no decrease, consistent with mixed results. The Metformin section reports decreases in CRP, but its only explicit hsCRP finding is no effect; it therefore does not substantiate the claim that hsCRP decreases were observed with metformin. The GLP-1 RA section also reports mixed findings, so the broader comparison of consistency is not clearly established. (LLM, conf=0.84)
Experimental — accuracy not yet measured
GLP-1 receptor agonists have anti-inflammatory effects, including reducing CRP.
“They have also been shown to have anti-inflammatory effects, including reducing CRP.9,10”
From Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials (2023) · cites this paper as [10]
Liraglutide has been associated with significant reductions in CRP in people with obesity and/or type 2 diabetes.
“Liraglutide, a GLP-1 analogue closely related to semaglutide, has also been associated with significant reductions in CRP in people with obesity and/or type 2 diabetes.10”
From Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials (2023) · cites this paper as [10]

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Authors: Katsiki, N., & Ferrannini, E.
Affiliations: Aristotle University of Thessaloniki (GR)
Istituto di Fisiologia Clinica (IT)
Corresponding author: Ferrannini, Ele
ORCID: Katsiki, Niki
Ferrannini, Ele
Venue: Journal of Diabetes and its Complications
Publisher: Elsevier BV
Published: 2020-12
Volume: 34
Issue: 12
Pages: 107723
ISSN: 0891-6632 (ISSN-L)
1056-8727
DOI: 10.1016/j.jdiacomp.2020.107723
PMC: PMC7448766
OpenAlex: W3080877256
Cited by: 91
References: 158
Citations by year: 2026: 7 · 2025: 6 · 2024: 13 · 2023: 17 · 2022: 24 · 2021: 21 · 2020: 3
FWCI: 2.49
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Diabetes and its Complications (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Boehringher Ingelheim/Lilly&Co.
AstraZeneca
Janssen
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: antidiabetic drugs, anti-inflammatory activity, COVID-19 pandemic, inflammation, diabetes mellitus, metformin, SGLT2 inhibitors, GLP-1 receptor agonists, SGLT1 inhibitors, C-reactive protein, interleukin-6, ferritin, glycemic control, SARS-CoV-2
MeSH terms: Sitagliptin Phosphate, Sodium-Glucose Transporter 2 Inhibitors, Pioglitazone, COVID-19, SARS-CoV-2, Glucagon-Like Peptide-1 Receptor Agonists, Anti-Inflammatory Agents, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Inflammation, Metformin, Risk Factors, Comorbidity, Dipeptidyl-Peptidase IV Inhibitors

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Anti-inflammatory properties of antidiabetic drugs: a “promised land” in the COVID-19 era?

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