Semaglutide (Ozempic®) - Novo Nordisk

Natalie Roy, PharmD, MHealth Neurology Clinic

Indication: Semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

Mechanism of Action: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that reduces fasting and postprandial blood glucose by stimulating insulin secretion and inhibiting glucagon secretion. By selectively binding to and activating the GLP-1 receptor, there is also a minor delay in gastric emptying in the early postprandial phase. Semaglutide has a long half-life due to albumin binding, which results in decreased renal clearance and protection from metabolic degradation.

Dosage and Administration: Semaglutide is a subcutaneous injection used in the abdomen, thigh, or upper arm. The dose starts at 0.25 mg once weekly for the first four weeks, then increases to 0.5 mg once weekly thereafter. The dose can be increased to a maximum of 1 mg once weekly if additional glycemic control is needed after four weeks of the 0.5 mg weekly dosage. Semaglutide can be administered at any time of day, with or without meals. If a dose is missed, it is recommended to administer within five days of the missed dose.


Monotherapy: In a 30-week double-blind trial, 388 patients with T2DM inadequately controlled with diet and exercise were randomized to semaglutide 0.5 mg or semaglutide 1 mg or placebo once weekly. The mean changes from baseline to week 30 compared to placebo for Hemoglobin A1c (HbA1c) were -1.2% for the 0.5 mg dose and -1.4% for the 1 mg dose. The mean changes from baseline to week 30 compared to placebo for weight were -2.6 kg for the 0.5 mg dose and -3.5 kg for the 1 mg dose.

Combination with metformin and/or sulfonylurea: In a 56-week open-label trial, 813 patients with T2DM on one to two oral antidiabetic medications (metformin, sulfonylurea, or thiazolidinedione) were randomized to semaglutide 1 mg or exenatide 2 mg once weekly. Treatment with semaglutide resulted in a statistically significant -0.5% HbA1c improvement compared to exenatide.


Adverse effects: Hypoglycemia, abdominal pain, constipation, diarrhea, nausea, vomiting
Serious adverse effects: Medullary thyroid carcinoma, pancreatitis, diabetic retinopathy
Contraindications: Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2

Place in Therapy: Semaglutide 0.5 and 1 mg subcutaneous weekly injections as monotherapy or in combination with other antihyperglycemic therapies significantly improved HbA1c compared with placebo or active antihyperglycemic comparators, including weekly exenatide 2 mg subcutaneous injections. Fasting plasma glucose, percentage of patients attaining HbA1c less than 7%, and weight were also improved versus comparator groups. Per the 2018 American Diabetes Association Standards of Medical Care in Diabetes, metformin is still regarded as the first-line therapy of choice. Semaglutide, and other GLP-1 agonists, can be recommended second-line or as add-on therapy to metformin.

Cardiovascular and Renal Benefits: The SUSTAIN-6 clinical trial in patients with T2DM and high cardiovascular risk showed that once-weekly semaglutide 0.5 mg or 1 mg in addition to standard care was non-inferior and superior to placebo with regard to a reduction in major adverse cardiovascular events after 105 weeks of therapy. In this study, there was also a significant 23% absolute reduction in the risk of new or worsening nephropathy with semaglutide compared with placebo.


  1. Ozembic [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2017. Accessed February 12, 2018.

  2. American Diabetes Association. Standards of Medical Care in Diabetes 2018. Diabetes Care. 2018; 41(Suppl.1): S7-S12. Accessed February 23, 2018.