Case report of PLXNA4 variant associated with hyper-response to phentermine/topiramate pharmacotherapy: Potential genetic basis for superior weight loss response?

Background: Once thought to be primarily a result of lifestyle, it is now known that obesity has significant genetic components. Dozens of genes have been linked to obesity, and office-based genetic testing for obesity-associated genes is now readily available. As both pharmacotherapy and genetic testing for obesity become more accessible, pharmacogenetic personalization is becoming a reality. In this case report, a patient with a PLXNA4 polymorphism had a superior weight loss response to phentermine/topiramate therapy than has previously been reported in the literature. Thus, variants in PLXNA4 may provide a genetic basis for this patient's superior response to weight loss pharmacotherapy and cardiovascular risk factor reduction. Methods: In this case study, office-based genetic testing was utilized to identify the presence of variants in nearly 80 genes that have been linked to obesity in a patient who had hyper-responsive weight loss results on phentermine/topiramate pharmacotherapy. Results: A variant of the PLXNA4 gene, which has known pathogenic variants linked to genetic obesity syndromes, was identified in this patient who had a superior weight loss response to phentermine/topiramate pharmacotherapy. Conclusion: Due to overlapping molecular pathways, it is possible that PLXNA4 variants convey a superior weight-loss response and therefore superior cardiovascular risk factor reduction phentermine/topiramate therapy. Further studies are needed to examine the relationship between PLXNA4 variants and weight loss with phentermine/topiramate pharmacotherapy.

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series.

Objective: Despite being a major cause of preventable death worldwide, alcohol use disorder (AUD) currently has only 3 FDA-approved pharmacotherapies. The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide has shown promise in preclinical studies for reducing alcohol consumption, but there are currently no randomized clinical trials that associate a decline in AUD symptoms with semaglutide use. This case series presents 6 patients with positive AUD screenings who were treated with semaglutide for weight loss. All subsequently exhibited significant improvement in AUD symptoms.Methods: Retrospective chart review was utilized to identify patients treated with semaglutide for weight loss who also had positive screenings for AUD on the Alcohol Use Disorder Identification Test (AUDIT; score > 8 considered positive) prior to initiation of semaglutide therapy. Six patients were identified who met these criteria. A paired t test was utilized to compare initial AUDIT scores with AUDIT scores after initiation of semaglutide therapy.Results: All 6 identified patients (100%) had significant reduction in AUD symptomatology based on AUDIT score improvement following treatment with semaglutide (mean decrease of 9.5 points, P < .001).Conclusions: This case series is consistent with preclinical data and suggests that GLP-1RAs have strong potential in the treatment of AUD. Additional randomized, placebo-controlled clinical studies are needed to fully assess the efficacy of semaglutide in treating AUD.