Genetic instruments for GLP-1R activation were selected based on associations with traits linked to drug target effects, such as body mass index (BMI) and glycated hemoglobin (HbA1c)
injections of 100 nmol kg 1 MK-801 ( n = 7 mice and n = 4 cages), 100 nmol kg 1 GLP-1 ( n = 6 mice and n = 3 cages), 100 nmol kg 1 , GLP-1MK-801 ( n = 6 mice and n = 3 cages), co-administration of 100 nmol kg 1 GLP-1 and 100 nmol kg 1 MK-801 ( n = 6 mice and n = 3 cages) or vehicle (isotonic saline, n = 7 mice and n = 4 cages) for 14 days
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Phase Cag introduction Weeks 9-12 Tirzepatide 5.0 mg/week (hold) Cagrilintide 0.25 mg/week Notes Add cagrilintide at the lowest dose
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