Anti-diabetics and antimicrobials: Harmony of mutual interplay

Table 1 Examples of antimicrobial activities of some antidiabetic drugs

Antidiabetic drug	Antimicrobial activity	Proposed mechanism	Ref.
Metformin	Antibacterial	Activation of the AMPK-mediated phagocytosis and production of mROS	[170]
		Disruption of the outer membrane permeability	[170]
		Down regulation of the Q.S encoding genes and mitigate the bacterial virulence	[19,186]
	Anti-TB	Increasing the production of β-defensin-2, -3 and -4 which diminish bacterial growth and multiplication	[178]
		Inhibition of mitochondrial complex-I which is analogous to mycobacterial NDH-I complex	[176]
		Activation of T regulatory and CD8 memory T cells responses activity	[177]
Sitagliptin	Antibacterial	Downregulation of the Q.S encoding genes, occupy the Q.S receptors and diminish bacterial virulence	[18,19,186]
	Anti-COVID-19	Reduction of the inflammation intensity	[190,191]
		Targeting viral proteins	[192]
		Binding to viral spikes	[193]
	Antibiofilm	Targeting enzyme XPDAP, analogous to mammalian enzyme DPP IV	[187]
Vildagliptin	Antibiofilm	Targeting enzyme XPDAP, analogous to DPP IV	[187]
	Anti-amoebic	-	[188]
Saxagliptin	Antibiofilm	Targeting enzyme XPDAP, analogous to DPP IV	[187]
Pioglitazone	Antibacterial	Increasing phagocytosis and production of reactive oxygen species in phagocytes	[197,198]
Tolbutamide	Antibacterial and antifungal	-	[205]
2nd generation sulfonylureas	Antifungal	Inhibition of the NLRP3 inflammasome	[206]
	Antibacterial	Prevention of inflammasome effector IL-1β	[207]
Glimepiride	Anti-amoebic	-	[188]
Repaglinide	Anti-amoebic	-	[188]
Glucagon-like Peptide-1	In HIV treatment	Reduction of HIV-associated metabolic adverse effects	[212]
α-glucosidase inhibitors	Antibacterial	Targeting bacterial glucosidase	[220]
	Antiviral and anti-COVID	Alter glycosylation in viral life cycle	[221]

mROS: Mitochondrial reactive oxygen species; IL: Interleukin; AMPK: Adenosine monophosphate-activated protein kinase; XPDAP: X-prolyl dipeptidyl peptidase; Q.S: Quorum sensing; COVID-19: Coronavirus disease 2019; HIV: Human immunodeficiency virus.