[Product Monograph Template - Schedule D]

1 OZEMPIC (semaglutide injection) Product Monograph Page 1 of 56 PRODUCT Monograph INCLUDING PATIENT MEDICATION INFORMATION OZEMPIC semaglutide injection 2 mg/pen ( mg/mL) Pre-filled pen delivering doses of mg or mg and Pre-filled pen delivering doses of 1 mg ATC code: A10BJ Antihyperglycemic Agent glucagon - like Peptide-1 (GLP-1) Receptor Agonist Novo Nordisk Canada Inc. 101-2476 Argentia Road Mississauga, Ontario L5N 6M1 Submission Control No: 202059 Date of Approval: January 4, 2018 OZEMPIC (semaglutide injection) Product Monograph Page 2 of 56 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION .. 3 SUMMARY PRODUCT INFORMATION.

2 3 3 INDICATIONS AND CLINICAL USE .. 3 CONTRAINDICATIONS .. 4 WARNINGS AND PRECAUTIONS .. 4 ADVERSE REACTIONS .. 9 DRUG INTERACTIONS .. 13 DOSAGE AND ADMINISTRATION .. 15 OVERDOSAGE .. 16 ACTION AND CLINICAL PHARMACOLOGY .. 16 STORAGE AND STABILITY .. 22 DOSAGE FORMS, COMPOSITION AND PACKAGING .. 23 PART II: SCIENTIFIC INFORMATION .. 25 PHARMACEUTICAL INFORMATION .. 25 CLINICAL TRIALS .. 25 DETAILED PHARMACOLOGY .. 33 TOXICOLOGY .. 33 REFERENCES .. 36 PART III: PATIENT MEDICATION INFORMATION .. 37 OZEMPIC (semaglutide injection) Product Monograph Page 3 of 56 OZEMPIC (semaglutide injection) PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION Route of Administration Dosage Form / Strength Clinically Relevant Nonmedicinal Ingredients Subcutaneous Injectable, mg/mL disodium phosphate dihydrate, propylene glycol, phenol, and water for injections. For a complete listing see Dosage Forms, Composition and Packaging section.

3 DESCRIPTION OZEMPIC contains semaglutide, a glucagon - like peptide-1 (GLP-1) receptor agonist (or GLP-1 analog) with 94% sequence homology to human GLP-1. The peptide backbone is produced by yeast fermentation and includes three amino acid substitutions to allow for attachment of an albumin-binding C-18 fatty diacid with a hydrophilic spacer and to increase stabilisation against degradation by the enzyme dipeptidyl-peptidase 4 (DPP-4). The molecular weight of semaglutide is approximately 4 kilodalton. OZEMPIC is a clear and colourless solution with a pH of OZEMPIC is provided in a pre-filled multi-dose disposable pen, which contains the drug solution, semaglutide, in a mL cartridge, equivalent to 2 mg semaglutide. See DOSAGE FORMS, COMPOSITION AND PACKAGING. INDICATIONS AND CLINICAL USE OZEMPIC is indicated for the once-weekly treatment of adult patients with type 2 diabetes mellitus to improve glycemic control, in combination with: diet and exercise in patients for whom metformin is inappropriate due to contraindication or intolerance.

4 Metformin, when diet and exercise plus maximal tolerated dose of metformin do not achieve adequate glycemic control. metformin and a sulfonylurea, when diet and exercise plus dual therapy with metformin and a sulfonylurea do not achieve adequate glycemic control. basal insulin with metformin, when diet and exercise plus basal insulin with metformin do not achieve adequate glycemic control (see CLINICAL TRIALS). OZEMPIC (semaglutide injection) Product Monograph Page 4 of 56 OZEMPIC has not been studied in combination with prandial insulin (short acting). OZEMPIC is not a substitute for insulin. OZEMPIC should not be used in patients with Type 1 diabetes mellitus (formerly known as insulin-dependent diabetes mellitus or IDDM) or for the treatment of diabetic ketoacidosis. See DOSAGE AND ADMINISTRATION for information on adjustment of doses of concomitant medications when adding OZEMPIC to the treatment regimen.

5 Geriatrics (> 65 years) OZEMPIC was studied in a limited number of patients 75 years of age or older (see WARNINGS AND PRECAUTIONS, Special Populations; DOSAGE AND ADMINISTRATION; and ACTION AND CLINICAL PHARMACOLOGY sections). Pediatrics ( < 18 years of age) The safety and efficacy of OZEMPIC have not been studied in pediatric populations. OZEMPIC is not indicated for use in pediatric patients. CONTRAINDICATIONS OZEMPIC is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). See WARNINGS AND PRECAUTIONS. OZEMPIC is contraindicated in patients with hypersensitivity to OZEMPIC or to any of the product components. See WARNINGS AND PRECAUTIONS. OZEMPIC should not be used during pregnancy or breastfeeding. WARNINGS AND PRECAUTIONS Serious Warnings and Precautions Risk of Thyroid C-cell Tumours Semaglutide causes treatment-dependent thyroid C-cell tumours at clinically relevant exposures in both genders of rats and mice (see PART II, TOXICOLOGY).

6 It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be ruled out by clinical or nonclinical studies. OZEMPIC is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should be counseled regarding the risk and symptoms of thyroid tumors (see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, Adverse Drug Reactions and Toxicology). General OZEMPIC (semaglutide injection) Product Monograph Page 5 of 56 OZEMPIC should not be used in patients with type 1 diabetes mellitus or for the treatment of patients with diabetic ketoacidosis. OZEMPIC should not be administered intramuscularly. Carcinogenesis and Mutagenesis Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures (see PART II, TOXICOLOGY).

7 It is unknown whether semaglutide causes thyroid C-cell tumors, including MTC, in humans as human relevance could not be determined. Thyroid C-cell tumors in rodents are a known class effect for GLP-1 receptor agonists. In clinical trials, there were no cases of MTC observed in patients treated with OZEMPIC . Counsel patients regarding the potential risk for MTC with the use of OZEMPIC and inform them of symptoms of thyroid tumors ( a mass in the neck, dysphagia, dyspnea, persistent hoarseness). It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate the potential risk of MTC, and such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Patients with thyroid nodules noted on physical examination or neck imaging obtained for other reasons should be referred to an endocrinologist for further evaluation.

8 Although routine monitoring of serum calcitonin is of uncertain value in patients treated with OZEMPIC if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation. (see ADVERSE REACTIONS, Adverse Drug Reaction Overview and Clinical Trial Adverse Drug OZEMPIC is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Endocrine and Metabolism Pancreatitis Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. In glycemic control trials (see Table 3), acute pancreatitis was confirmed by adjudication in 7 OZEMPIC -treated patients ( cases per 100 patient years) versus 3 in patients treated with another GLP-1 receptor agonist ( cases per 100 patient years); no cases were seen with placebo or other drug classes. One case of chronic pancreatitis was confirmed in an OZEMPIC -treated patient.)

9 In a 2 year trial (SUSTAIN 6), acute pancreatitis was confirmed by adjudication in 8 OZEMPIC -treated patients ( cases per 100 patient years of observation) and 10 placebo-treated patients ( cases per 100 patient years of observation), both on a background of standard of care. There were no cases of chronic pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis. After initiation OZEMPIC (semaglutide injection) Product Monograph Page 6 of 56 of OZEMPIC , observe patients for signs and symptoms of pancreatitis. If pancreatitis is suspected, OZEMPIC should be discontinued; if confirmed, OZEMPIC should not be restarted. Consider anti-diabetic therapies other than OZEMPIC in patients with a history of pancreatitis. Hypoglycaemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving OZEMPIC in conjunction with sulfonylurea or basal insulin may have an increased risk of hypoglycemia.

10 The risk of hypoglycaemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin when initiating treatment with OZEMPIC . See DOSAGE AND ADMINISTRATION, and ADVERSE REACTIONS. Other incretin drugs Concomitant use of OZEMPIC with other GLP-1 analogs, DPP-4 inhibitors and SGLT-2 inhibitors has not been studied. It is unknown if concomitant use of drugs acting via similar pathways affects the efficacy and safety of OZEMPIC . Immune Hypersensitivity Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any GLP-1 receptor agonist, including OZEMPIC . If a hypersensitivity reaction occurs, the patient should discontinue OZEMPIC and promptly seek medical advice. Ophthalmologic Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC ( ) compared to placebo ( ).