Research
Hormonal
Metabolic and bariatric surgery (MBS) often results in substantial weight regain in patients with monogenic or syndromic obesity, particularly those with MC4R pathway variants, making it less effective than targeted pharmacotherapy for these groups.
If you have a known genetic form of obesity, discuss the long-term risks of bariatric surgery with your doctor. Studies show that patients with MC4R pathway variants often regain significant weight after surgery because the underlying genetic hunger drive remains unaddressed.
ModerateRefutesMEDIUM confidence
Furthermore, case reports of patients with highly penetrant monogenic or syndromic obesity who underwent MBS show that any initial postoperative weight lost is frequently regained [22,23,103].
Why this rating
Based on retrospective analyses and case reports, which are lower on the evidence hierarchy than RCTs.
Source
Differentiating monogenic and syndromic obesities from polygenic obesity: Assessment, diagnosis, and management
Angela Fitch et al. · Obesity Pillars · 2024
DOI 10.1016/j.obpill.2024.100110
narrative_reviewCited 18×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Traditional nontargeted weight management strategies (lifestyle changes, anti-obesity medications, and metabolic/bariatric surgery) are frequently inadequate for patients with highly penetrant monogenic or syndromic obesity caused by rare genetic variants in the melanocortin-4 receptor (MC4R) pathway.Good
- Targeted pharmacotherapy with MC4R agonists (specifically setmelanotide) is efficacious and safe for reducing body weight and hunger in patients with specific genetic causes of obesity, including POMC deficiency, LEPR deficiency, and Bardet-Biedl syndrome (BBS).Good
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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