PAD Refills

How does the weight loss effect of tirzepatide subcutaneous (Zepbound™) compare to semaglutide subcutaneous (Wegovy^®) in people without type 2 diabetes?

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Conclusion: In people with a BMI ≥ 30 or ≥ 27 plus a comorbidity excluding type 2 diabetes, tirzepatide at a target dose of 10 or 15 mg once a week has a larger effect on measures of weight loss at 72 weeks compared to semaglutide at a target dose 1.7 or 2.4 mg once a week. The incidence of common gastrointestinal adverse events does not differ meaningfully between the two medications but whether there is a difference in the risk of serious adverse events remains unclear.

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.  

In Canada, tirzepatide is indicated for chronic weight management while semaglutide has an indication for both chronic weight management and to reduce the risk of non-fatal myocardial infarction in adults with cardiovascular disease and BMI ≥ 27 kg/m².² There is an ongoing cardiovascular trial for tirzepatide which is due in 2027.³

The SURMOUNT-5 Trial was a 72-week, randomized but open-label trial comparing tirzepatide to semaglutide in adults with a BMI ≥ 30 or a BMI ≥ 27 and at least one comorbidity (e.g., hypertension, dyslipidemia, obstructive sleep apnea).⁴ The primary outcome was percentage change in body weight from baseline to week 72. Participants were titrated up to a maximum tolerated dose of tirzepatide (10 or 15 mg once a week) or semaglutide (1.7 or 2.4 mg once a week). At week 72, over 80% were receiving maximum doses. All participants received lifestyle modification counseling addressing diet and physical activity. If a participant’s BMI decreased to 22 during the trial, the medication dose could be reduced.

Table: Tirzepatide vs semaglutide for chronic weight management (SURMOUNT-5 Trial)5
751 participants: mean age 45, mean BMI 39, 65% female, 76% White		Tirzepatide subcutaneous: target 10 or 15 mg once a week	Semaglutide subcutaneous: target 1.7 or 2.4 mg once a week
% change in body weight at week 72		21.6%	15.4%
Proportion who lost ≥ 10% weight		86.7%	67.3%
Proportion who lost ≥ 20% weight		54.8%	31.9%
Proportion who lost ≥ 30% weight		22.4%	6.9%
Nausea, constipation, diarrhea		43.6%, 27.0%. 23.5%	44.4%. 28.5%. 23.4%
Efficacy estimands from Supplementary Table S2

While the open-label design of this trial could introduce biases, the results of SURMOUNT-5 are consistent with the blinded, principal trials comparing tirzepatide and semaglutide each to placebo where tirzepatide has a larger average effect on body weight loss.¹ Gastrointestinal adverse events were the most common adverse events with tirzepatide and semaglutide leading to discontinuation of treatment in 2.7% and 5.6% of participants respectively.⁴

Tirzepatide is more costly than semaglutide at their maximum approved doses: approximately $10,600 per year (tirzepatide 15 mg) versus $5,600 per year (semaglutide 2.4 mg).⁵

The SURMOUNT-5 trial was too small to address an important and outstanding practice question: Is there a difference between tirzepatide and semaglutide in the risk of serious adverse events (e.g., those leading to death, disability, hospitalization)?

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¹BC PAD Service Medications for Weight Loss (November 2024 updated); ²Health Canada Drug Product Database; ³SURMOUNT-MMO NCT0555651; ⁴SURMOUNT-5 NEJM 2025 (PMID:40353578); ⁵McKesson PharmaClick (accessed July 14,2025) drug cost excludes markup and professional fees.