Hormonal
Weight regain after discontinuation of GLP-1-based AOMs is an inherent feature of current pharmacological strategies, but future interventions such as gene therapy (GLP-1PGTx) or gradual dose-tapering may mitigate this by sustaining hormonal signals or allowing hormonal adaptation.
Stopping GLP-1 medications currently leads to weight regain for most people due to hormonal adaptations. While lifestyle changes help, they may not be enough to counteract these hormonal shifts. Future treatments, such as gene therapy or careful dose-tapering, aim to sustain weight loss after stopping, but these are not yet standard care. Patients should plan for long-term management strategies with their providers.
Cessation of treatment often results in weight regain and recurrence of obesity... In another yet-to-be published work, diet-induced obese mice given a one-time intraperitoneal injection of adeno-associated virus gene therapy, GLP-1PGTx... effectively sustains fat mass loss following semaglutide discontinuation.
Why this rating
Based on preclinical gene therapy data and speculative clinical strategies (tapering).
Source
Why are we still in need for novel anti-obesity medications?
Aaron Novikoff et al. · The Lancet Regional Health - Europe · 2024
DOI 10.1016/j.lanepe.2024.101098
More from this paper
- Current GLP-1-based anti-obesity medications (AOMs) achieve profound acute body weight loss (up to 25%) but are associated with significant real-world treatment discontinuation (up to 50%) due to gastrointestinal side effects and lack of lifestyle counseling, necessitating novel formulations with improved tolerability.Good
- Combining GLP-1 receptor agonists with myostatin or activin type II receptor inhibitors (e.g., bimagrumab, trevogrumab, garetosmab) preserves or increases lean mass while enhancing fat loss, addressing the risk of sarcopenia and metabolic slowdown associated with standard AOM therapy.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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