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Why Weight Regain Occurs : Biological adaptations that promoted weight gain initially remain present Appetite and food preoccupation often return when medication stopped Metabolic rate may decrease during weight loss (adaptive thermogenesis) Hormonal changes that defend against weight loss persist Long-Term Management : Most individuals require ongoing medication for sustained weight loss maintenance This is similar to other chronic disease treatments (e.g., blood pressure medications) Obesity is a chronic disease requiring long-term management Strong lifestyle habits help minimize regain but may not prevent it entirely Discuss any plans to discontinue medication with healthcare provider to develop appropriate tapering plan and maintenance strategies

Villanuevas team were particularly interested in changes in acylcarnitines levels in the blood

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Maarbjerg and Jeanett Borregaard were employees of Novo Nordisk A/S at the time of conduct of the trial and preparation of this manuscript and are shareholders of Novo Nordisk A/S (current affiliation of SJM: Zealand Pharma A/S, Sborg, Denmark