Chronic Semaglutide Treatment in Diabetic Mice

Treatment was initiated 7 weeks after AAV administration and 6 weeks post-UNx (Figure 1). Randomization and stratification to treatment was based on fed blood glucose and body weight measured one week before treatment start. db/db UNx-ReninAAV mice (n = 14–15 per group) received (q.d.) vehicle (0.5% methyl cellulose, s.c.), semaglutide (30 nmol/kg, s.c., Bachem AG, Bubendorf, Switzerland), or combined semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o., MedChemExpress, Monmouth Junction, NJ, USA) for 11 weeks. A dose-escalation scheme was implemented to reduce expected initial effects of semaglutide treatment, as transient GLP-1R-induced discomfort in rodents, including taste aversion and pica behavior, is typically observed within the first 2–3 days of treatment [21 (link)].