Resistant and Refractory Obesity: The Complexity of Anti-Obesity Therapy Failure

Area of Science:

• Endocrinology and Metabolism
• Pharmacology
• Obesity Medicine

Background:

• Pharmacotherapy is crucial for obesity management, but treatment failure is frequent in clinical practice.
• Failure manifests as poor response, early discontinuation, or weight regain, highlighting a gap between trial efficacy and real-world results.

Purpose of the Study:

• To explore the multifaceted reasons for resistance and refractoriness to anti-obesity therapies.
• To emphasize the significance of identifying pretreatment predictive factors for personalized obesity management.

Main Methods:

• This review synthesizes current knowledge on factors influencing anti-obesity medication (AOM) effectiveness.
• It examines clinical, biological, genetic, and socioeconomic determinants of treatment outcomes.

Main Results:

• AOM effectiveness is impacted by psychiatric comorbidities, socioeconomic factors, individual characteristics (e.g., body composition, microbiome), and pharmacokinetic/pharmacotherapeutic issues.
• Genetic variations, immunological responses (e.g., antidrug antibodies), concomitant medications, and endocrine disorders also contribute to therapy resistance.

Conclusions:

• Resistance to AOMs is complex and multifactorial, involving a combination of patient-specific, medication-related, and environmental influences.
• Identifying individuals at risk for inadequate response through pretreatment factors is essential for tailoring personalized strategies and improving long-term obesity management, especially in challenging cases.