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For non-diabetic obesity, the cleanest comparison is between two separate trials: STEP 1 (semaglutide 2.4 mg, Wilding et al., NEJM 2021): 14.9% body weight loss at 68 weeks SURMOUNT-1 (tirzepatide 15 mg, Jastreboff et al., NEJM 2022): 20.9% body weight loss at 72 weeks A roughly 6 percentage point gap in average weight loss favors tirzepatide

Semaglutide can be administered before or after food, but it should be kept in mind that the injection should be given on the same day of the week regardless of the timing

In the tirzepatide group, TDD of insulin as well as basal and bolus insulin doses (expressed either in U/day or U/kg/day) decreased significantly from baseline and to a greater extent than in the semaglutide and control groups at all time points (least square mean TDD of insulin at 12 months: tirzepatide group, 26.4 U/day [0.13 U/kg/day]

Rapid or divided dosing does not improve weight loss outcomes

Dosing Comparison# Survodutide Dosing# Based on Phase 2 trial data and ongoing Phase 3 protocols: Route : Once-weekly subcutaneous injection Dose escalation : Starting dose of 0.25 mg with gradual titration Maintenance doses studied : 2.4 mg, 4.8 mg, and 6.0 mg weekly in Phase 2 Optimal dose : 4.8 mg and 6.0 mg showed greatest efficacy in Phase 2 weight loss trials MASH dosing : Similar dose range evaluated in hepatic endpoints trials Titration rationale : Gradual escalation minimizes GI side effects and allows metabolic adaptation to glucagon receptor activation Tirzepatide Dosing# FDA-approved dosing protocols: Route : Once-weekly subcutaneous injection Starting dose : 2.5 mg weekly for 4 weeks Dose escalation : Increase by 2.5 mg every 4 weeks as tolerated Maintenance doses : 5 mg, 10 mg, or 15 mg weekly Maximum dose : 15 mg weekly Formulation : Prefilled single-dose pens (Mounjaro/Zepbound) and prefilled syringes Storage : Refrigerated