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Stacking both therapies increases the risk of cumulative GI side effects and potential dehydration, especially during the critical first 4 weeks of tirzepatide initiation when patients are establishing tolerance

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187,188 Since 2007, genome-wide association studies (GWAS) and next-generation sequencing (NGS) have identified different genetic variants associated with IR, including PPAR , IRS1 , IGF1 , NAT2 , KLF14 , GCKR , FTO , TCF7L2 , TMEM163 , MC4R , SC4MOL , TCERG1L , and ARL15 184,189,190 by influencing insulin action via different regulatory mechanisms