The Other Side of Weight Loss: Addressing Nutritional Risk During Antiobesity Medication Therapy

As antiobesity medications (AOMs) like semaglutide and tirzepatide become increasingly accessible, they are reshaping the landscape of obesity treatment. With average weight loss outcomes exceeding 15%, these medications mark a new era in metabolic management. Yet, as emphasized in a recent review by Almandoz et al. (2024) in Obesity, this progress comes with an important caveat: the heightened risk of malnutrition—both preexisting and treatment-induced.

While AOMs work by dampening appetite and reducing energy intake, they also override the brain’s adaptive hunger signals, disrupting a core physiological feedback loop evolved to defend energy availability. This pharmacologic appetite suppression—beneficial for weight reduction—may exacerbate nutrient deficiencies, particularly in individuals already experiencing subclinical or exposure-related malnutrition.

We must acknowledge that obesity itself can be a form of malnutrition—not from insufficient calories, but from abnormal energy partitioning, low circulating nutrient availability, and metabolic inefficiency. This paradox lies at the heart of Exposure-Related Malnutrition (ERM), a state in which the body's adaptive effort to cope with chronic stress and substrate mismatch diverts resources away from repair and maintenance, setting the stage for functional decline.

By further reducing food intake and hunger cues, AOMs can unintentionally accelerate this process, worsening ERM and increasing the risk of muscle loss, micronutrient deficiency, and impaired recovery capacity—especially if nutritional needs are not proactively addressed.

This is where the 5 A’s model—Ask, Assess, Advise, Agree, Assist—offers a practical framework, but it must be reimagined through a personalized, nutrition-aware lens:

• Ask about both overt and silent signs of malnutrition, food access, and psychosocial stressors.

• Assess for ERM risk factors—low protein intake, micronutrient gaps, sarcopenia, and inflammation—before and during AOM therapy.

• Advise on nutrient-dense foods, hydration, protein prioritization, and individualized supplementation when needed.

• Agree on holistic health goals, not just weight loss, that support metabolic resilience.

• Assist with structured follow-up, lab monitoring, and referrals to dietitians for medical nutrition therapy.

For AOMs to fulfill their promise, we must go beyond prescribing and actively protect the nutritional integrity of our patients. In doing so, we shift the focus from weight loss alone to true healthspan extension—preserving strength, cognition, recovery, and vitality.

References

Almandoz JP, et al. Nutritional considerations with antiobesity medications. Obesity. 2024;32(9):1613–1631. https://doi.org/10.1002/oby.24067