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Special Population Considerations Population pharmacokinetic analyses revealed: Body weight influences GLP2 exposure (approximately 1.1% change per kg) Renal impairment (including end-stage renal disease) does not significantly impact pharmacokinetics Hepatic impairment (mild to severe) does not require dose adjustments Age, sex, race, and ethnicity do not have clinically relevant effects on GLP2 pharmacokinetics Study Populations GLP2 clinical research has included the following participant groups: Adults with type 2 diabetes Primary focus of SURPASS trials (over 6,000 participants) Adults with obesity or overweight SURMOUNT trials for chronic weight management Participants with metabolic comorbidities Including metabolic syndrome, prediabetes Heart failure patients with HFpEF and obesity SUMMIT trial population Adults with obstructive sleep apnea and obesity SURMOUNT-OSA studies Various demographic populations Multinational studies across diverse racial and ethnic groups Research Limitations & Regulatory Status Critical Gaps in Current Evidence Despite an extensive clinical development program, important limitations remain in the GLP2 evidence base

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The functions of mammalian cellular clock proteins are additionally regulated through posttranslational modifications through various kinases, methylation, polyadenylation, histone modifications, and non-coding RNAs (Mendoza-Viveros et al., 2017

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