Table 2.

Glycaemic effects of potential pharmacological agents for COVID-19

Drugs	Mechanisms of action	Source of data	Blood glucose	Insulin sensitivity or resistance	β-Cell function
Camostat mesylate	Serine protease (TMPRSS2) inhibitor	Human studies	↓ Patients with new-onset DM and chronic pancreatitis172	–	–
		Animal studies	↓ BG175; ↓ PPG215	↓ Insulin level173; ↓ insulin resistance175	↓ Insulin secretion (reversed by GIP)216,217
		Cells/organs	↓ BG176	↓ Insulin level174	–
		Patients with DM and/or insulin resistance	↓ BG175; ↓ PPG215	↓ Insulin level173, ↓ insulin resistance175	–
Chloroquine or hydroxychloroquine	Blockade of virus entry and immunomodulation	Human studies	↓ HbA1c (refs178,180,218); ↓ FPG178; ↓ PPG or BG180; ↓ hazard ratio for incident new-onset DM by 38% in patients with RA219; hypoglycaemia180,181	↑ Insulin sensitivity178; ↑ hepatic insulin sensitivity220	↑ β-Cell function178
		Cells/organs	–	–	GLUT4 translocation and glucose uptake: ↓ in adipocytes221, ↑ in muscle cells222
		Patients with DM and/or insulin resistance	↓ HbA1c (refs178,180,218); ↓ FPG178; ↓ PPG or BG180; ↓ hazard ratio for incident new-onset DM by 38% in patients with RA219; hypoglycaemia180,181	–	–
Protease inhibitors	Proteolytic processing of viral proteins	Human studies	↑ FPG185; ↑ BG186,223; ↑ in patients with new-onset DM187	↑ Insulin level185,223,224; ↓ insulin sensitivity185,223,224; ↓ glucose clearance185; ↓ non-oxidative glucose disposal224,225	↓ β-Cell function185; ↓ first-phase insulin release185
		Animal studies	–	–	↓ GLUT4 activity226,227
		Cells/organs	–	–	↓ GLUT4 activity228 or mRNA229
RNA-dependent RNA polymerase inhibitors	Inhibition of RNA-dependent RNA polymerase	Animal studies	↓ FPG191	↓ Insulin level191; ↓ insulin resistance193	–
		Patients with DM and/or insulin resistance	↓ FPG191	↓ Insulin level191; ↓ insulin resistance193	–
IL-6 receptor inhibitors	IL-6 antagonism, suppressing the production of inflammatory molecules	Human studies	↓ HbA1c (ref.230)	↓ Insulin level194; ↓ insulin-to-glucose ratio194; ↑ insulin sensitivity194; ↓ insulin resistance194	–
		Animal studies	↓ Glucose intolerance231	–	–
		Cells/organs	–	–	↓ Transplanted islet cell death231
		Patients with DM and/or insulin resistance	↓ HbA1c (ref.230); ↓ glucose intolerance231	–	↓ Transplanted islet cell death231
IL-1 receptor inhibitors	IL-1 antagonism	Human studies	↓ HbA1c (refs196,232); ↓ FPG232; no effect on HbA1c and BG in patients with recent-onset T1DM198	↑ C-peptide secretion196; ↑ proinsulin-to-insulin ratio196	–
		Animal studies	↓ Glucose intolerance231	–	–
		Cells/organs	–	–	↑ Insulin secretion in transplanted islets231; ↓ transplanted islet cell death231
		Patients with DM and/or insulin resistance	↓ HbA1c (ref.232); ↓ FPG232; no effect on HbA1c and BG in patients with recent-onset T1DM198	No effect on C-peptide secretion in patients with T1DM198	↑ Insulin secretion in transplanted islets231; ↓ transplanted islet cell death231
IL-1β inhibitors	IL-1β antagonism	Human studies	No effect on HbA1c in patients with recent-onset T1DM198	No effect on C-peptide secretion in patients with recent-onset T1DM198	–
		Patients with DM and/or insulin resistance	No effect on HbA1c in patients with recent-onset T1DM198	No effect on C-peptide secretion in patients with recent-onset T1DM198	–
JAK1 and JAK2 inhibitors	Suppressing JAK–STAT signalling, inhibition of clathrin-medicated endocytosis, immunosuppression	Animal studies	↓ Reversal of new-onset DM in NOD mice200	↓ Insulin level233	–
		Patients with DM and/or insulin resistance	↓ DM development200	↓ Insulin level233	–
BTK inhibitor	Immunomodulatory effect on macrophages, reducing the production of cytokines	Animal studies	↓ BG201	–	–
TNF inhibitors	TNF antagonism	Human studies	↓ FBG205,234,235; ↓ HbA1c (refs230,235); ↓ patients with new-onset DM and RA and psoriasis236	↓ Insulin resistance205,235,237; ↑ insulin sensitivity205,237	↑ β-Cell function205
		Patients with DM and/or insulin resistance	↓ FBG205,234,235; ↓ HbA1c (refs230,235)	↓ Insulin resistance205; ↑ insulin sensitivity205	↑ β-Cell function205
Corticosteroids206,238	Anti-inflammatory effects	Human studies	↑ HbA1c; ↑ BG (mainly PPG)	↑ Insulin resistance; ↓ insulin sensitivity	↓ Insulin production and secretion

BG, blood glucose; BTK, Bruton’s tyrosine kinase; COVID-19, coronavirus disease 19; DM, diabetes mellitus; FPG, fasting plasma glucose; GIP, glucose-dependent insulinotropic polypeptide; GLUT4, glucose transporter type 4; JAK, Janus kinase; NOD, non-obese diabetic; PPG, postprandial glucose; RA, rheumatoid arthritis; STAT, signal transducer and activator of transcription; T1DM, type 1 diabetes mellitus; TMPRSS2, transmembrane protease serine 2; TNF, tumour necrosis factor.