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Acarbose effect decreased with concomitant administration of diuretics, steroids, thyroid products, estrogens, phenytoin, calcium channel blockers Digestive enzymes decreases effect of miglitol and acarbose F. DosingDosed TID and taken with the first bite of each large meal Due to side effects both drugs must be started low and titrated to max dose Maximum response occurs by 6 months G. MonitoringWhen used in combination with a hypoglycemic agent, patients must be taught the importance of treating hypoglycemia with dextrose since these agents will block the absorption of more complex sugars like sucroseLiver function tests for acarbose H. Place in therapyMonotherapy or combination therapy in the treatment of Type 2 DM o↓ A1C 0.5-1% Advantages: weight neutral, targets postprandial hyperglycemia (good for patients with erratic eating habits), no hypoglycemia, can be used in patients with sulfa allergy, Disadvantages: GI side effects, dosed with meals Combination Products ExamplesGlyburide and Metformin (Glucovance®)Glipizide and Metformin (Metaglip™)Pioglitazone and metformin (Actoplusmet®)Sitagliptan and metformin (Janumet®)Place in TherapyMay help ↑ compliance in patients who take the individual medications in dosages that are available in the combination products May be more expensive Incretin MimeticsExenatide (Byetta®and Bydureon®), Liraglutide (Victoza®), dulaglutide (Trulicity®), semaglutide(Ozempic®and Rybelsus®)A. Mechanism of Action17
Incretin hormones (GLP-1, GIP) are produced by the small intestine in response tofood that act to stimulate insulin secretion Exenatide is a GLP-1 analog that stimulates the production of insulin in response to high blood glucose levels, inhibits the release of glucagons after meals, increases satiety (which decreases food intake), and slows the rate of gastric emptying Does not impair the body’s reaction to hypoglycemia May aid in preservation and formation of pancreatic beta cellsB. Adverse Effects Nausea (44%), vomiting, diarrhea, dyspepsia Dizziness, headache Hypoglycemiawhen used with sulfonylureaC. Precautions / Contraindications Not a substitute for insulin in Type 1 patients Can cause hypoglycemia when used with sulfonylureas – empirically reduce dose of oral med when starting exenatide Do not use in patients with severe renal impairment (CrCl <30mL/min) or end-stage renal disease Do not use in patients with severe GI disease or gastroparesis Post marketing reports of pancreatitis, so use caution if history of pancreatitisD. Drug-Drug Interactions Alters rate and extent of absorption of oral medications Meds requiring peak concentrations (oral contraceptives, antibiotics) – take 1 hour before or at least 2 hours after exenatideE. Dosing Byetta Initial – 5 mcg SQ BID within 60 minutes of the morning & evening meal, after 1 month increase to 10mcg SQ BID if desiredo Decrease sulfonylurea dose when initiating exenatideBydureon – 2mg SQ once weeklyVictoza initial – 0.6mg SQ daily for 1 week, increase to 1.2mg SQ daily for 1 week