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Findings
What does this study add?
- At 26 weeks, a higher dose of tirzepatide modulated a cluster of metabolites and lipids associated with insulin resistance, obesity, and future T2D risk.
- After 26 weeks, 54 metabolites had a significant change from baseline in response to tirzepatide 15 mg, compared to 6 with dulaglutide, and 0 with placebo.
- Compared to baseline and placebo, there were decreased levels of BCAA and their direct catabolic products, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate.
- The changes were significantly larger with tirzepatide compared with dulaglutide – and directly proportional to reductions in HbA1c, insulin resistance indices, and proinsulin levels.
- Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species.
