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Abbreviations ALT alanine aminotransferase ANOVA analysis of variance AST aspartate transaminase AUC area under the concentrationtime curve BMI body mass index C cohort cAMP cyclic adenosine monophosphate C max maximum observed concentration EC 50 half maximal effective concentration ECG electrocardiogram E max maximal effective concentration EOT end of treatment FBG fasting blood glucose GAN-DIO Gubra-Amylin diet-induced obese GI gastrointestinal GIP glucose-dependent insulinotropic polypeptide GIPR glucose-dependent insulinotropic polypeptide receptor GLP-1 glucagon-like peptide-1 GLP-1R glucagon-like peptide-1 receptor GPCR G proteincoupled receptor GSIS glucose-stimulated insulin secretion ipGTT intraperitoneal glucose tolerance test ivGTT intravenous glucose tolerance test iWAT inguinal white adipose tissue HbA1c glycated hemoglobin HOMA-IR Homeostasis Model Assessment of Insulin Resistance MAD multiple-ascending dose MASH metabolic dysfunction-associated steatohepatitis MC4RKO melanocortin receptor 4 knock-out NAS nonalcoholic fatty liver disease activity score OGTT oral glucose tolerance test PD pharmacodynamic PK pharmacokinetic SAD single-ascending dose SAE serious adverse event SD Standard deviation SE Standard error SEM Standard error of the mean t 1/2 apparent (estimated) terminal elimination half-life T2D type 2 diabetes TEAE treatment-emergent adverse event t max time to maximum concentration 1

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