PAD Refills

How does the weight loss effect of oral semaglutide (Rybelsus^®) compare to subcutaneous semaglutide (Ozempic^®, Wegovy^®)?

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Conclusion: When compared to placebo, oral semaglutide (targeting 50 mg once a day) and subcutaneous semaglutide (targeting 2.4 mg once a week) have similar effects on bodyweight (15% mean bodyweight loss). Oral semaglutide for type 2 diabetes (up to 14 mg once a day) is approved by Health Canada, but the higher dose for weight loss is not yet approved. 

The BC Provincial Academic Detailing (PAD) service’s topic Medications for weight loss looks at the evidence for tirzepatide, semaglutide, liraglutide, naltrexone-bupropion and orlistat.¹ Visit www.bcpad.ca to book a session with an academic detailing pharmacist in your area.

Semaglutide formulations currently available in Canada

Semaglutide formulations currently available in Canada: Indications, cost, BC PharmaCare coverage2,3
Brand name	Health Canada indication	Maximum dose	Annual drug cost	BC PharmaCare coverage
Ozempic®	Type 2 diabetes	Subcut: 2 mg once a week	$3060 (1 mg dose)	Limited coverage (up to the 1 mg dose)
Wegovy®	Chronic weight management and to reduce the risk of non-fatal myocardial infarction in adults with cardiovascular disease and BMI ≥ 27	Subcut: 2.4 mg once a week	$5500	Non-benefit
Rybelsus®	Type 2 diabetes	Oral: 14 mg once a day	$2800	Non-benefit

a) Weight loss in type 2 diabetes trials: In type 2 diabetes trials, where weight loss is typically a secondary outcome, oral semaglutide (targeting 14 mg once a day) lowers bodyweight by approximately 3 kg and subcutaneous semaglutide (targeting 1 mg once a week) by approximately 5 kg.⁴

b) Weight loss trials: The principal semaglutide weight loss trials enrol people with BMI ≥ 30 or BMI ≥ 27 plus a comorbidity (e.g., obstructive sleep apnea, dyslipidemia or hypertension) and target higher doses: oral semaglutide 50 mg once a day, subcutaneous semaglutide 2.4 mg once a week.^5,6 In both oral and subcutaneous semaglutide trials, the weight loss effect at 68-weeks is similar: ~15% mean bodyweight loss with ~85% of participants achieving at least 5% bodyweight loss. The formulations have not been compared head-to-head. Oral semaglutide at the 50 mg dose is not yet approved by Health Canada and is not yet available.

c) Potential for altered skin sensations: Similar to subcutaneous semaglutide, gastrointestinal adverse events were the most common adverse event in the oral semaglutide weight loss trial.^5,6  However, the incidence of altered skin sensations (including paraesthesia, dysesthesia, hyperesthesia) with oral semaglutide is increased compared to placebo (13% vs. 1%) thus emerging as a newly-identified adverse event.⁵ The US Food and Drug Administration is now evaluating the need for further regulatory action for the GLP1 agonist class.⁷

d) Cardiovascular trials: In a cardiovascular trial enrolling people with a BMI ≥ 27 and a history of cardiovascular disease, subcutaneous semaglutide (2.4 mg once a week) reduced the risk of major adverse cardiovascular events and death from any cause.⁸ A cardiovascular trial with oral semaglutide (14 mg once a day) in people with type 2 diabetes is completed but is not yet reported.⁹ We could not identify an ongoing oral semaglutide cardiovascular trial in people without type 2 diabetes.

¹BC Provincial Academic Detailing Service 2024: Medications for weight loss; ²Health Canada Drug Product Database; ³McKesson PharmaClick (accessed Dec 11, 2024) – drug cost excludes markup and professional fees; ⁴SHI BMJ 2023;e074068 (PMID:37024129); ⁵OASIS 1 Lancet 2023 (PMID: 37385278); ⁶STEP 1 NEJM 2021 (PMID:33567185); ⁷US Food & Drug Administration Adverse Event Reporting System (Jan-Mar 2024); ⁸SELECT NEJM 2023 (PMID:37952131); ⁹SOUL NCT0391432