Anti‐inflammatory effects of sodium‐glucose cotransporter‐2 inhibitors in COVID‐19

Abstract

The ongoing pandemic of COVID-19 is intrinsically a systemic inflammatory disorder; hence, those patients suffering an underlying chronic inflammatory disease such as diabetes mellitus are at high risk of severe complications. Preventing or suppressing the inflammatory responses are of importance in diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a newly introduced anti-diabetic drugs that have hypoglycemic effects through the urinary excretion of glucose. They also have an anti-inflammatory potential in diabetes patients, in addition to improving glycemic control, and while there is no direct data available in diabetic patients with COVID-19 disease, there is evidence that suggests that SGLT2i can reduce systemic inflammation and diminish the cytokine storm effect via several cellular mechanisms. In the current review, our aim was to classify and describe the molecular and cellular pathways by which SGLT2i have anti-inflammatory effects in diabetic patients with COVID-19 disease.

MAFLD Pandemic: Updates in Pharmacotherapeutic Approach Development

“…Reduction of inflammation, steatosis and fibrosis has been suggested as a beneficial effect on the liver, for which the clinical efficacy of SGLT2 inhibitors is being investigated in numerous RCTs (1,59,60). Among all SGLT2 inhibitors, dapagliflozin and empagliflozin have come the longest way [61]. The efficacy of dapagliflozin is still being assessed in a placebo-controlled phase 3 RCT (NCT05308160), which is expected to enroll a total of 75 patients with MAFLD diagnosed with grade 2 or higher steatosis detected by FibroScan device by the end of April 2024 [61,62].…”

“…Among all SGLT2 inhibitors, dapagliflozin and empagliflozin have come the longest way [61]. The efficacy of dapagliflozin is still being assessed in a placebo-controlled phase 3 RCT (NCT05308160), which is expected to enroll a total of 75 patients with MAFLD diagnosed with grade 2 or higher steatosis detected by FibroScan device by the end of April 2024 [61,62]. In another placebo-controlled phase 3 RCT, the so-called DEAN study (NCT03723252), a total of 154 patients with biopsy confirmed MASH and metabolic risk factors were recruited in China, with the primary endpoint being histological improvement after 12 months of dapagliflozin therapy.…”

“…Tirzepatide is a novel drug that is approved for T2DM and obesity and is being intensively trialled for other indications, including MAFLD, as it has already shown beneficial effects on MAFLD biomarkers in patients with T2DM. This drug belongs to "twincretins" group as it is a dual GLP-1 and GIP receptor agonist (61,72,82). At the beginning of 2024, the Phase 2 RCT SYNERGY-NASH (NCT04166773) was completed, which was conducted in MASH patients to evaluate the safety and efficacy of tirzepatide.…”