Hormonal
Tirzepatide and semaglutide are the only obesity management medications (OMMs) achieving greater than 10% total body weight loss (TBWL) at study endpoints, with tirzepatide uniquely associated with a significantly higher proportion of patients achieving ≥25% TBWL.
If you are seeking significant, clinically meaningful weight loss (over 10% of body weight), current evidence strongly supports using tirzepatide or semaglutide over older oral medications. Tirzepatide shows the highest efficacy, with a unique ability to help a larger proportion of patients lose 25% or more of their body weight. Be aware that these are long-term treatments; stopping them typically leads to regaining most of the lost weight, so they should be viewed as ongoing management for obesity, not a short-term fix.
The estimated TBWL% was greater than 10% only for semaglutide and tirzepatide... Only tirzepatide was associated with a greater proportion of patients achieving at least 25% TBWL reduction (odds ratio [95% confidence interval]: 33.8 [18.4–61.9], P < 0.001).
Why this rating
Based on a network meta-analysis of 56 RCTs involving 60,307 patients with 'high' GRADE evaluation for the primary endpoint.
Source
A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults
Barbara McGowan et al. · Nature Medicine · 2025
DOI 10.1038/s41591-025-03978-z
More from this paper
- Semaglutide significantly reduces Major Adverse Cardiovascular Events (MACE) and hospitalization for heart failure (HHF) risk, while Tirzepatide significantly reduces HHF risk, offering cardiovascular protection beyond weight loss.Good
- Tirzepatide is the only obesity management medication shown to significantly reduce the Apnea-Hypopnea Index (AHI) and achieve remission of Obstructive Sleep Apnea Syndrome (OSAS) in patients with obesity.Moderate
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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