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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 onlyCrCl 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

 Sitagliptin 100mg daily – $100 (ODB coverage)

Source: http://www.ccpn.ca/docs/Whats_New_in_Diabetes_H_Halapy.pdf

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