Hormonal
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.
While GLP-1 drugs like semaglutide and tirzepatide produce significant weight loss, real-world adherence is a major hurdle due to gastrointestinal side effects. To maximize success, patients should utilize flexible, patient-determined titration schedules rather than fixed rapid escalation, and consider prophylactic anti-emetics if needed, as these strategies improve long-term tolerability and adherence.
a recent study analyzing real-world, longitudinal, medical claims databases showed that 39% of patients with obesity treated with GLP-1R agonists discontinue relative to their trials within the first 3 months. At 12 months, treatment discontinuation may even increase up to 50%... Multiple real-world studies demonstrate that reduced treatment tolerability is significantly associated with treatment discontinuation and decreased likelihood for treatment reinitiation.
Why this rating
Based on multiple real-world observational studies and clinical trial data cited.
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
- 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
- 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.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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