Oral and Injectable Non-insulin Antihyperglycemic Agents
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1 Appendix 5: Diabetes Education and Medical Management in Adults with Diabetes Oral and Injectable Non-insulin s This directive will be implemented by RPhs, RNs or RDs who have been deemed authorized implementers. Note: Medications discontinued or placed on hold should be reviewed within hours by the RPh, RN, or RD in collaboration with the physician. TABLE 1: List of Medications Implemented Under this Directive with Detailed Indications/ Contraindications Oral / Non-insulin Injectable Alpha-Glucosidase Inhibitor Acarbose (Glucobay) Maximum daily dose 300 mg/day with first bite of meal Biguanides Metformin (Glucophage) Maximum dose 2550 mg/day +/- or bedtime Extended Release Metformin (Glumetza, Glucophage XR) Maximum dose 2000 mg/daily Gastrointestinal (GI) side effects Inadequate blood Frequency of hypoglycemia GI side effects Change the timing of the dose (i.e. moving lunch dose to HS to improve fasting sugars) Inadequate blood Frequency of hypoglycemia GI side effects Blood glucose remains above target (7 mmol/l) consistently Blood glucose below 4 mmol/l consistently Contraindications: diabetic ketoacidosis, cirrhosis, inflammatory bowel disease, intestinal obstruction or predisposition to obstruction Not recommended as initial therapy in people with marked hyperglycemia (A1C to 8.5%) Gastrointestinal side effects Treat hypoglycemia with glucose tablets, milk or honey Contraindications: Type 1 Diabetes, history of lactic acidosis, ketoacidosis, renal impairment (CrCl < 60 ml/min), congestive heart failure, excessive ETOH (acute or chronic), hepatic dysfunction, pregnancy, or gastrointestinal side effects Hold for 48 hours if undergoing radiologic studies with administration of iodinated contrast material Page 1
2 Insulin Secretagogues Sulfonylureas: Gliclazide (Diamicron) Maximum dose is 320 mg/day with Gliclazide MR (Diamicron MR) Maximum dose is 120 mg/day take once daily at breakfast Glimepiride (Amaryl) 1 mg 8 mg/day, take once daily with breakfast Frequent hypoglycemia Inadequate blood Contraindications: Type 1 Diabetes, hypersensitivity to sulfonamides, severe renal or hepatic impairment, diabetic ketoacidosis, pregnancy, breastfeeding Hypoglycemia and weight gain are more common with glyburide Consider using other class(es) of oral antihyperglycemic agents first in patients at high risk of hypoglycemia (i.e. the elderly) Hypoglycemia with insulin Glyburide (Diabeta) 1.25 mg 20 mg/day with Non-sulfonylureas: Nateglinide (Starlix) 180 mg 540 mg/day take before Repaglinide (GlucoNorm) 0.5 mg 16 mg/day with Insulin Sensitizers Thiazolidinediones (TZDs): Pioglitazone (Actos) 15 mg - 45 mg/day take the same time each day Rosiglitazone (Avandia) 2 mg - 8 mg/day take with Discontinue if hypoglycemia persists 1-2 times per week Blood glucose remains above target (7 mmol/l) consistently Blood glucose below 4 mmol/l consistently This class of drug is no longer approved for inclusion in this directive. While these drugs are still currently available, they are associated with potentially serious risks, outlined below. Implementers who feel one of these drugs is necessary should consult with the patient s physician. Rosiglitazone should be used only when all other oral antidiabetic agents, in monotherapy or in combination, do not result in adequate glycemic control or are inappropriate due to contraindications or intolerance. It is associated with an increased risk of ischemic heart disease, including myocardial infarction. Health Canada recommends that physicians obtain written consent from patients before prescribing this drug. Findings from new studies reveal that there is a potential increased risk of bladder cancer in patients treated with pioglitazone-containing products. Risk factors for bladder cancer should be assessed before initiating treatment with pioglitazone (risks include age, smoking, family history of bladder cancer, exposure to chemicals in the workplace, certain cancer treatments and radiation therapy). Page 2
3 DPP4 Inhibitors Sitagliptin (Januvia) 100 mg once daily Linagliptin (Trajenta) 5 mg once daily Saxagliptin (Onglyza) 2.5 mg 5 mg once daily Nasopharyngitis Inadequate glucose control May need to reduce dose of insulin or insulin secretagogue if used in combination therapy Contraindications: Hypersensitivity, Type 1 Diabetes Renal dose adjustments required for egfr <50 for sitagliptin and saxagliptin Cases of acute pancreatitis have been reported, monitor for signs and symptoms of pancreatitis and use with caution in patients with history of pancreatitis GLP-1 Analogues Liraglutide (Victoza) SubQ: 0.6 mg once daily for first week, then increase to 1.2 mg daily, Maximum: 1.8 mg daily Exenatide (Byetta) SubQ: Immediate release: 5mcg twice daily, may increase to 10mcg twice daily after 1 month; Extended Release: 2mg once weekly Nausea (extended duration) Inadequate glucose control Contraindications: Hypersensitivity, pregnancy, breast-feeding, personal or family history of Medullary Thyroid Cancer, Multiple Endocrine Neoplasia syndrome type 2 (MEN2) Use is not recommended in hepatic impairment Cases of acute and chronic pancreatitis have been reported, monitor for signs and symptoms of pancreatitis and use with caution in patients with history of pancreatitis SGLT2 Inhibitors Canagliflozin (Invokana) 100 mg 300 mg daily Dapagliflozin (Forxiga) 5 mg 10 mg daily Empagliflozin (Jardiance) 10 mg 25 mg daily Hypoglycemia Nausea and hyperkalemia Discontinue if recurrent genital mycotic infection or if develops ketoacidosis Contraindications: Type 1 Diabetes, hypersensitivity, renal impairment (egfr <45 ml/min for canagliflozin, empagliflozin; <60ml/min for dapagliflozin) Do not initiate therapy or increase dose to 300mg if egfr <60 ml/min May cause ketoacidosis, even with glucose values < 13.9mM; use with caution in patients predisposed to ketoacidosis (e.g., alcohol abuse, caloric restriction) May Increase risk of genital mycotic infections and urinary tract infections that may become serious (urosepsis, pyelonephritis); assess patients with symptoms suggestive of UTI and consider discontinuation of Page 3
4 drug May cause symptomatic hypotension due to intravascular volume depletion Page 4
5 Summary of Therapeutic Notes for Oral and Injectable Non-insulin s: Key Adverse Effects Gastrointestinal upset, loose bowels (biguanide, alphaglucosidase inhibitor) Hypoglycemia (secretagogues less with gliclazide, glimepride, nateglinide and replaglinide than with glyburide), GLP-1 analogues, SGLT2 inhibitors. Edema, fluid retention (insulin sensitizers) Moderate weight gain (insulin secretagogues, insulin sensitizers) Urinary tract infections, genital mycotic infections, ketoacidosis (SGLT2 inhibitors) Key precaution/contraindications Hepatic disease (glyburide, biguanide, insulin sensitizers, DPP4I, GLP1 Analogues) Significant renal insufficiency (biguanide, sulfonylureas, DPP4I, GLP1 Analogues) Significant cardiac failure (biguanide, insulin sensitizers, DPP4I, GLP1 Analogues) Page 5
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