TABLE 4

Oral and injectable noninsulin antidiabetic agents

Drug	Mechanism of action	Advantages	Side effects and disadvantages	Use in chronic kidney disease
Biguanide metformin	Insulin sensitizer Decreases hepatic glucose production	No hypoglycemia^a No weight gain	Gastrointestinal Vitamin B¹² deficiency Lactic acidosis	Contraindicated if serum creatinine > 1.5 mg/dL in men and 1.4 in women in US (in most other countries may use if glomerular filtration rate [GFR] ≥ 30 mL/min)
Sulfonylureas glyburide, glipizide, glimepiride	Stimulate insulin release Decrease postprandial glucose	Less expensive	Hypoglycemia Weight gain	Due to risk of hypoglycemia, must be used with caution (short-acting glipizide preferred)
Meglitinides repaglinide, nateglinide	Stimulate insulin release Decrease postprandial glucose		Hypoglycemia Weight gain Expensive	Safer than sulfonylureas
Thiazolidinediones pioglitazone	Insulin sensitizer in muscle and adipose tissue	No hypoglycemia^a	Weight gain Edema Bone fractures	Safe but can cause fluid retention, limiting its use in chronic kidney disease
Alpha-glucosidase inhibitors acarbose, miglitol	Slow carbohydrate absorption, decrease postprandial glucose	No hypoglycemia^a	Gastrointestinal	Contraindicated if serum creatinine > 2 mg/dL
GLP-1 receptor agonists exenatide, liraglutide, albiglutide	Activate GLP-1 receptor Increase insulin Decrease glucagon Decrease gastric emptying, increase satiety	Weight loss No hypoglycemia^a	Gastrointestinal Pancreatitis Medullary thyroid cancer Expensive	Contraindicated if GFR < 30 mL/min
Dipeptidyl peptidase-4 inhibitors sitagliptin, saxagliptin, linagliptin, alogliptin	Inhibit breakdown of GLP-1 Increase insulin Decrease glucagon	No hypoglycemia^a	Pancreatitis Expensive	Safe Require dose reduction except linagliptin
Dopamine agonist bromocriptine	Stimulates dopamine receptors	No hypoglycemia^a	Hypotension	Unknown
Bile acid sequestrant colesevelam	Unknown	No hypoglycemia^a	Constipation Increases triglycerides	Unknown
SGLT2 inhibitors canagliflozin, dapagliflozin, empagliflozin	Inhibit sodium-glucose cotransporter-2 (SGLT2), reducing glucose reabsorption and increasing urinary glucose excretion	No hypoglycemia^a	Mycotic infections Urinary tract infections	Contraindicated if GFR < 45 mL/min

↵a No hypoglycemia when used alone, but may cause hypoglycemia when used with insulin or sulfonylureas.