Research
Hormonal
Tirzepatide (5-15 mg weekly) produces superior weight loss compared to semaglutide and placebo in adults with obesity, with dose-dependent efficacy.
Tirzepatide is a weekly injection that can lead to significant weight loss (up to ~21% in trials). It works by targeting two hormones (GIP and GLP-1). Side effects like nausea are common but often temporary. It is approved for adults with obesity or overweight with health issues.
WeakSupportsVERY_HIGH confidence
In an RCT of 2539 adults with BMI ≥ 30, or BMI ≥ 27 with at least 1 weight-related complication, but without diabetes, participants were randomly assigned to receive tirzepatide 5 mg, 10 mg, 15 mg, or placebo weekly for 72 weeks... At 72 weeks, the mean weight change with 5 mg, 10 mg, and 15 mg was –15.0%, –19.5%, and –20.9%, respectively, compared with –3.1% with placebo.
Why this rating
Level 1a evidence from a large RCT (SURMOUNT-1).
Source
Pharmacotherapy for obesity management in adults: 2025 clinical practice guideline update
Sue D. Pedersen et al. · Canadian Medical Association Journal · 2025
DOI 10.1503/cmaj.250502
clinical_guidelineCited 32×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Obesity pharmacotherapy is recommended against for compounded medications or unapproved medications due to safety and efficacy concerns.Good
- Long-term use of FDA/Health Canada-approved obesity pharmacotherapies (semaglutide, tirzepatide, liraglutide, naltrexone-bupropion, orlistat) combined with health behavior changes produces clinically meaningful weight loss and prevents weight regain upon discontinuation.Weak
- Obesity pharmacotherapy reduces the risk of major adverse cardiovascular events (MACE) in patients with established atherosclerotic cardiovascular disease (ASCVD) and BMI ≥ 27, independent of diabetes status.Weak
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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