Macrophage modulation with dipeptidyl peptidase-4 inhibitors: A new frontier for treating diabetic cardiomyopathy?

Table 2 Effects of antidiabetic drugs on macrophage function in diabetic cardiomyopathy

Drug class	Drug examples	Effects on macrophages	Related mechanisms	Ref.
Dipeptidyl peptidase-4 inhibitors	Teneligliptin, linagliptin, sitagliptin	Reduce pro-inflammatory cytokine production (IL-1β, IL-6), promote M2 polarization, and inhibit NLRP3 inflammasome activation	Increased glucagon-like peptide-1 levels, reduced oxidative stress, and modulation of nuclear factor-kappaB signaling pathway	[3,14,24]
Metformin	Metformin	Reduces M1 polarization, increases M2 polarization, suppresses nuclear factor-kappaB signaling, and inhibits mitochondrial dysfunction	AMPK activation, reduced reactive oxygen species generation, and modulation of metabolic pathways	[13,17]
Sodium-glucose cotransporter 2 inhibitors	Dapagliflozin, empagliflozin	May indirectly affect macrophage function through improved cardiac function and reduced inflammation	Sodium-glucose cotransporter 2 inhibition leads to diuresis and natriuresis, and may improve cardiac remodeling	[18,25]
Glucagon-like peptide-1 receptor agonists	Liraglutide, dulaglutide	Promote M2 polarization, reduce pro-inflammatory cytokine production, and may improve cardiac contractility	Reduce oxidative stress, and enhance insulin sensitivity	[26-28]
Thiazolidinediones	Pioglitazone	Have anti-inflammatory properties, and improve insulin sensitivity	Peroxisome proliferator-activated receptor-γ activation, and reduced nuclear factor-kappaB signaling	[29,30]

AMPK: AMP-activated protein kinase; IL: Interleukin.