Table 4.

Noninsulin drug therapy for NODMa

ClassPrinciple Mechanism of ActionExampleEffect on HbA1cAdverse EffectsMetabolism/EliminationAltered Dosing in CKD
SulfonylureasInsulin secretagogueGlipizide Glyburide Glimepiride−1.0 to −2.0%HypoglycemiaMajor: HepaticNo
MeglitinidesInsulin secretagogueRepaglinide Nateglinide−0.6%HypoglycemiaMajor: CYP2C8 and 3A4CrCl >40 ml/min: No CrCl <40 ml/min: Gradual introduction
BiguanidesDecrease hepatic glucose productionMetformin−1.0 to −1.7%Nausea Lactic acidosis (extremely rare)Major: Renal tubular secretionAvoid with more severe levels of kidney dysfunction
TZDIncrease insulin sensitivityPioglitazone Rosiglitazone−1.0 to −1.9%Weight gain Fluid retentionMajor: CYP2C8 Minor: CYP3A4No
α-Glucosidase inhibitorsDecrease intestinal glucose absorptionAcarbose−0.3 to −0.6%Nausea FlatulenceMajor: Fecal Minor: RenalNot recommended if creatinine >2 mg/dl
GLP-1 receptor agonistsStimulates glucose mediated insulin secretion Inhibits glucagon Induces weight loss due to delayed gastric emptying and appetite suppressionExenatide−0.4 to −0.8%Nausea, other gastrointestinalMajor: RenalNot recommended if CrCl ≤30 ml/min
DPP-IV inhibitorsIncreases GLP-1Sitagliptin−0.5%MinimalMajor: Renal Minor: CYP3A4, 2C8Dosage reduction
  • a CKD, chronic kidney disease; CrCl, creatinine clearance; DPP-IV, dipeptidyl peptidase-IV; GLP-1, glucagon-like peptide-1.