Table 4.

Classification of hypoglycemic agents based on hypoglycemic mechanism and organ protective effects

Treatment needs	Classification by mechanism of hypoglycemia or target organ protection or safety	Medications
HYPOGLYCEMIC EFFECT	Dependent on pancreatic islet β cell function	Secretagogues
	Partly dependent on pancreatic islet β cell function	DPP-4i, GLP-1
	Independent of pancreatic islet β cell function	Metformin, AGI, SGLT-is, TZD, Insulin
CV BENEFITS	Glucose-dependent benefits	Secretagogues, DPP-4i, insulin
	Glucose-independent benefits	Pioglitazone, SGLT-is GLP-1: dulaglutide, semaglutide (SQ), liraglutide
	Possible glucose-independent benefits	Metformin, AGI
RENAL BENEFITS	Glucose-dependent benefits	Secretagogues, DPP-4i, insulin
	Glucose-independent benefits	SGLT-is GLP-1: dulaglutide, semaglutide (SQ), liraglutide
IMPACT ON BODY WEIGHT AND VISCERAL FAT	Weight-loss effect	Metformin, AGI, GLP-1, SGLT-is
	Weight-neutral effect	DPP-4i
	Weight gain but visceral fat loss	TZD
	Weight gain in non-overweight or non-obese patients	Secretagogues
	Weight-gain effect	Insulin
SAFETY BASED ON HYPOGLYCEMIC RISK	No significant hypoglycemic risk	Metformin, AGI, TZD, SGLT-is
	Low hypoglycemic risk	DPP-4i, GLP-1
	Moderate hypoglycemic risk	Secretagogues, basal insulin
	High hypoglycemic risk	Insulin (except for basal insulin)
SAFETY BASED ON IMPACT ON LIVER FUNCTION	Safe in mild to moderate liver function impairment	All hypoglycemic medications
	Safe in severe liver function impairment	Linagliptin, lixisenatide, dulaglutide, insulin

This table is modified according to Zhang et al.²¹¹

DPP-4i dipeptidyl peptidase-4 inhibitors, GLP-1 glucagon-like peptide-1, AGI α-glucosidase inhibitors, SGLT-is sodium-glucose cotransporter inhibitors, TZD thiazolidinediones, CV cardiovascular, SQ subcutaneous