Microsoft word - 07_whats new in diabetes_h halapy.doc
Antihyperglycemic Medications Trade Name Mechanism of Action A1C Reductions
1. Dosage reduction for renal dysfunction approved in the US only – CrCl 30-50mL/min use 50mg once daily, CrCl<30mL/min
2. Dosage reduction for renal dysfunction approved in the US only – CrCL <50mL/min use 2.5mg once daily. Dosage reduction
if patient is taking on a strong CYP 450 3A4/5 inhibitor use 2.5mg once daily.
3. Dosage reduction for renal dysfunction approved in the US – CrCl<30mL/min do not use, CrCl 30-50mL/min use maximum
5mcg bid, >50mL/min use 10mcg bid. In Canada, these agents are approved only for renal function of CrCl>50mL/min in the doses given in the above table.
Approved Indications: DPP-4 Inhibitors – combination with metformin or sulfonylurea or both. Sitagliptin also indicated as monotherapy in patients who do not tolerate both metformin and sulfonylurea. Liraglutide – with metformin or in combination with metformin + sulfonylurea Exenatide – received Notice of Compliance in Canada, not yet marketed SGLT-2 Inibitors – Phase III trials Contraindications: DPP-4 Inhibitors – renal impairment (in Canada), pregnant or breast-feeding, pediatrics Liraglutide - with family history of medullary thyroid carcinoma or MEN-2 syndrome, pregnant or breast-feeding women Side Effects: DPP-4 Inhibitors – increased risk of some infections (nasopharyngitis, bronchitis, urinary tract infections), GI distress, rare hypoglycemia on own but can worsen hypoglycemia caused by other drugs Liraglutide - ++ GI distress (nausea, vomting, diarrhea), rare hypoglycemia (higher rates of hypoglycemia when used in combination with sufonlyureas), injection site reactions, Increase in heart rate/ PR interval prolongation. Rare cases of pancreatitis reported. Pts need to warned about rare cases of medullary thyroid carcinoma in rats and mice; however, this has not been reported in humans. Exenatide - +++ nausea/ vomiting, diarrhea, rare hypoglycemia (higher rates of hypoglycemia when used in combination with sufonlyureas), injection site reactions, hypersensitivity reactions, rare reports of pancreatitis, renal impairment SGLT-2 Inhibitors - constipation, diarrhea, nausea, rare hypoglycemia, vaginal infections and urinary tract infections, decreased serum Mg, increased serum phosphate
Drug Interactions: DPP-4 Inhibitors -
– Saxagliptin metabolised by CYP3A4/5 – Unlikely to alter metabolic clearance of coadministered drugs – 3A4 inducers may decrease saxagliptin levels – 3A4 inhibitors did not alter levels saxagliptin levels (but some strong CYP450 3A4/5 inhibitors can be
– Sitagliptin not likely to have drug interactions
Liraglutide – potential for decreased absorption of narrow therapeutic index meds Exenatide - Warfarin – increase INR; potential for decreased absorption of narrow therapeutic index meds
Counselling Issues: DDP-4 Inhibitors – may be taken with or without food Liraglutide – inject once a day independent of meals, inject subcutaneously in abdomen, thigh, or upper arm. Store liraglutide pens in the refrigerator and keep out of sunlight; however, pen currently in use may be stored at room temperature for 30 days. Exenatide – inject twice a day independent of meals, inject subcutaneously in abdomen, thigh, or upper arm. SGLT-2 Inhibitors – take before morning meal Average Monthly Cost Comparison
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