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JAMA Neurology, 80(7), 730738

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Secondary Outcome: Secondary Outcomes: Changes in waist circumference, body fat, body lean mass, and metabolic risk factors including levels of plasma glucose, insulin sensitivity, serum lipids, and blood pressure Statistical Analysis Full details previously published 2 and can also be found in the STEP group statistical analysis plan at NEJM.org Statistical analysis approach sought strong control for type I error All endpoints addressing intervention efficacy were analyzed using intention-to-treat approach All endpoints addressing intervention safety were analyzed using per-protocol approach Efficacy endpoints analyzed using 2 estimands Treatment Policy Estimand: intention to treat analysis

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In this study, both the GLP-1MK-801-treated mice and the calorie-restricted mice exhibited improved insulin sensitivity relative to the vehicle treatment and both monotherapy control groups (Extended Data Fig