Research
Hormonal
GLP-1 agonists (e.g., semaglutide, liraglutide) and metformin can aid in weight management, but GLP-1 agonists do not reset the weight set point, leading to significant weight regain upon discontinuation.
GLP-1 agonists and metformin can help with weight loss, but they do not cure the underlying biological tendency to regain weight. If you use them, expect to use them long-term to maintain results. They are tools to manage weight, not a one-time fix.
GoodQualifiesHIGH confidence
To date, there is no evidence that they change the body weight set point so it is likely that individuals will regain the lost weight after discontinuation so these medications may need to be used long term.
Why this rating
Based on clinical trials and meta-analyses cited in the review.
Source
Our biology working against us in obesity: A narrative review on implications for management of osteoarthritis
Flavia Cicuttini et al. · Osteoarthritis and Cartilage Open · 2023
DOI 10.1016/j.ocarto.2023.100407
narrative_reviewCited 9×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Biological mechanisms, specifically a defended weight set point driven by genetic and epigenetic factors, actively oppose weight loss maintenance by altering hunger hormones and reducing energy expenditure, making long-term weight loss difficult without continuous intervention.Good
- Preventing 'weight creep' (0.5-1 kg/year gain) through low-intensity lifestyle interventions is a more achievable and effective strategy for OA management than focusing solely on significant weight loss in already obese individuals.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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