Pharmacogenomics of Medication‐Induced Weight Gain and Antiobesity Medications

Abstract

Obesity is a chronic, multifactorial disease associated with a large number of comorbidities. The clinical management of obesity involves a stepwise integrated approach, beginning with behavioral and lifestyle modification, followed by antiobesity medications, endobariatric procedures, and bariatric surgery. Weight gain and subsequent obesity are common side effects of medications, such as prednisone or antipsychotics. In this era of precision medicine, it is essential to identify patients at the highest risk of weight gain as a result of medication use. Pharmacogenomics could play an important role in obesity management by optimizing use of antiobesity medications as well as minimizing adverse weight gain. This review aims to provide a comprehensive analysis of the current literature on the role of pharmacogenomics in obesity and medication-induced weight gain. In summary, there are more robust studies of medication associated with weight gain and pharmacogenomics, and more studies are needed to understand the role of pharmacogenomics in antiobesity medications.

Association between CYP metabolizer phenotypes and selective serotonin reuptake inhibitors induced weight gain: a retrospective cohort study

“…Poor metabolizers taking escitalopram resulted in a greater rate of therapeutic failure, indicating the potential clinical value of CYP2C19 genotyping for individualization of escitalopram [ 38 ]. However, there has not been any difference in adverse drug events reported between pharmacogenomic tailored treatment compared with controls [ 8 , 9 , 32 ].…”

“…Studies have also examined genes related to weight gain and SSRIs, such as catechol-O-methyltransferase ( COMT), tryptophan hydroxylase 1 ( TPH1), HTR2C, and serotonin transporter gene (SLC6A4). The evidence shows that GG COMT and AA TPH1 genotypes have more weight gain outcomes than HTR2C and SLC6A4 polymorphism[ 9 , 16 , 37 ]. Our research did not cover the effect of other genes involved in the SSRI metabolisms; therefore, further research focusing on other enzymes involved in the SSRI metabolism is needed to understand the variability in weight gain response to this class of medication.…”

“…Because cytochrome P450 (CYP) enzymes contribute to phase I drug metabolism, CYP enzyme variation significantly impact treatment outcomes [ 8 ]. Pharmacogenomics offers the opportunity to optimize treatment considering these polymorphisms to develop a more personalized approach to antidepressant selection while reducing adverse drug events [ 9 ]. In 2013, the Clinical Pharmacogenetics Implementation Consortium (CPIC) developed dosing guidelines for paroxetine, citalopram, and sertraline based on their main metabolizer enzymes' phenotype status CYP2C19 and/or CYP2D6 .…”

“…Pharmacogenomics is a tool to personalize management in multiple areas, such as psychiatry and weight management [ 9 , 12 ]. Multiple mood disorder studies have evaluated SSRI responsiveness for depression and lithium therapy in bipolar illness in GWAS studies and polygenic risk scores analysis [ 13 – 15 ].…”

Biological Mechanism(s) Underpinning the Association between Antipsychotic Drugs and Weight Gain

“…Besides receptor binding profile and antipsychotic side-effects, the weight gain in patients treated with antipsychotics has been linked to individual and environmental characteristics. A meta-analysis identified 13 single-nucleotide polymorphisms that were significantly associated with AIWG [ 10 ], and the pharmacogenomics associated with drug-induced weight gain was reviewed by Sneha Singh and colleagues [ 11 ] and Soria-Chacartegui [ 12 ]. Children and adolescents seem to be especially vulnerable to AIWG [ 13 , 14 ].…”