Weight Loss in T2D

Tirzepatide produces dose-dependent weight loss in T2D trials: −7.0 to −9.5 kg (SURPASS-1, monotherapy vs placebo), −8.0 to −14.0 kg in later trials. Weight loss is relevant to this vault because it partially mediates tirzepatide’s HbA1c reduction (via improved insulin sensitivity) and kidney outcomes (via reduced intrarenal pressure). Post-hoc mediation analysis suggests approximately 50% of tirzepatide’s UACR reduction is attributable to weight loss. Separating weight-dependent from weight-independent drug effects is an important methodological issue in interpreting tirzepatide evidence.

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