Table 1.

Glucose-lowering medications with potential interfering effects on COVID-19

	Potential positive effects	Potential negative effects
Glucocorticoids34, 35	Anti-inflammatory effects	Risk of hyperglycaemia
ACE inhibitors and angiotensin II receptor blockers33, 36, 37	Increases expression of soluble ACE2; neutralises virus	Increased expression of membrane-bound ACE2 might increase virus entry (no clinical evidence)
Metformin38, 39	Stabilises ACE2; modulates ACE2–angiotensin II–AT1R axis; inhibits host–virus binding; inhibits mitochondrial complex I; protects endothelium and vasculature; decreases virus maturation	Risk of dehydration, lactic acidosis, chronic kidney disease, and acute kidney injury
SGLT2 inhibitors22, 40	Reduces viral load; positive effects on cardiovascular and renal functions	Risk of dehydration, diabetic ketoacidosis, and acute kidney injury
GLP-1 receptor agonists22, 41, 42	Anti-inflammatory effects; improves endothelial dysfunction; improves cardiovascular and renal functions	Reduces appetite and increases satiety; gastrointestinal symptoms
DPP-4 inhibitors40, 43, 44	Blocks virus uptake; reduces inflammatory response; well tolerated	Increases mortality in older patients (likely due to confounding by indication)
Insulin22, 45, 46, 47	Anti-inflammatory effects	Hypoglycaemia; high doses increase COVID-19 mortality

Of note, many of these results are retrospective and confounded by indications, patients' risk profiles, or severity of diseases. ACE=angiotensin-converting enzyme.