Currently, early response, defined as >5% weight loss in the first three months, appears to be the only predictor of long-term weight loss with anti-obesity medications (AOMs). Thus, in clinical practice, providers have little choice but to initially select AOMs based on physician/patient preference, medication interactions, comorbidities, risk of potential adverse events, or insurance coverage. This trial and error approach is both frustrating and a potential barrier to the effective use of AOMs.
Now, a paper by Andre Acosta and colleagues from the Mayo Clinic, published in OBESITY, shows that a phenotype-guided approach to prescribing AOMs leads to markedly better weight loss than the conventional approach.
In this pragmatic, real-world trial, 450 participants were first phenotyped using standardised tests to four phenotypes: hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). Of these, 312 phenotyped patients were randomly assigned to phenotype-guided or non-phenotype-guided treatment with phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide.
At 12 months, the phenotype-guided approach was associated with a 1.75 greater weight loss (15.9% vs. 9.0%) and the proportion of participants who lost >10% was 79% in the phenotype-guided group compared to 34% with non-phenotype-guided treatment group.
The authors conclude that it is possible to identify actionable phenotypes of obesity based on pathophysiology and behavior that elucidate human obesity heterogeneity, which can in turn be targeted to enhance weight loss outcomes of pharmacotherapy.
If confirmed in larger studies, these results could herald a major step forward in our ability to individualise obesity pharmacotherapy for maximum effect.
@DrSharma
Berlin, D
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