Table 3.

Oral Diabetic Agents

Medication Class	Mechanism of action	Medication	Usage in dialysis patients	Side effects
Sulfonylureas	Bind to receptor on pancreatic beta cell and stimulates insulin release	1st generation: Acetohexamide Chlorpropamide Tolazamide Tolbutamide	Avoid use of 1st generation agents in dialysis patients	Hypoglycemia Hypersensitivity in patients with sulfa allergies Nausea Abnormal liver function tests
		2nd generation: Glipizide Gliclazide Glimepiride Glyburide	Glipizide is the agent of choice
Meglitinides	Stimulate endogenous insulin secretion by regulation of ATP-dependent potassium channels on pancreatic beta cells	Repaglinide Nateglinide	Dose reductions not specified, but no clear guidelines Avoid use in dialysis patients	Hypoglycemia
Biguanides	Inhibits hepatic gluconeogenesis Decrease intestinal glucose absorption Improve peripheral insulin sensitivity	Metformin	Avoid use in dialysis patients	Lactic acidosis (incidence 0.03 cases per 1000 patientt-years; mortality 50%) Nausea Diarrhea Metallic taste
Thiazolidine-diones	Improves peripheral insulin sensitivity Suppresses hepatic gluconeogenesis May improve beta-cell function	Rosiglitazone (soley PPAR-gamma agonist) Pioglitazone (also has PPAR-alpha effects)	Restricted use by manufacturer Dose adjustment not required	Hypoglycemia Weight gain Fluid retention Edema Congestive heart failure (contraindicated in patients with New York Heart Association Class III and IV Congestive Heart Failure) Abnormal liver function tests Bone loss, decreased formation, increased fracture risk
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors	Promotes insulin release by deactivating the DPP-4 enzyme which is a deactivator of Glucagon-like Peptide-1 (which stimulates insulin secretion)	Sitagliptin Saxagliptin Linagliptin	Dose reduction by 75% Dose reduction to 25 mg po qday, given after dialysis Not well studied in dialysis patients	Pancreatitis Abnormal liver function tests Skin reactions
Glucagon-like Peptide 1 Analogues	Stimulate glucose-dependent insulin release from pancreatic beta cells Delays gastric emptying Inhibits glucagon release Decreases appetite	Exenatide Liraglutide	Avoid use in dialysis patients Avoid use in dialysis patients	Nausea Pancreatitis Diarrhea
Amylin Analogues	Stimulate glucose- dependent insulin release from pancreatic beta cells Delays gastric emptying Inhibits glucagon release Decreases appetite	Pramlintide	Avoid use in dialysis patients	Nausea Hypoglycemia
Alpha-glucosidase inhibitors	Inhibit alpha-glucosidases (gastrointestinal enzymes that convert complex polysaccharide carbohydrates into monosaccharides) which gastrointestinal glucose absorption	Acarbose Miglitol	Avoid use in dialysis patients due to limited study	Abdominal discomfort Diarrhea Flatulence
Sodium-glucose cotransporter 2 inhibitors	Inhibit proximal tubular reabsorption of filtered glucose and promote renal excretion of glucose Reduces weight Reduces blood pressure	Canagliflozin Dapagliflozin	Avoid use in dialysis patients	Vulvovaginal candidiasis Genital tract infections Urinary tract infections