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Lean tirzepatide when: Maximum weight loss is the goal (target greater than 20%) You have T2D with significant insulin resistance (SURPASS-2: 11.2 kg tirzepatide vs 5.7 kg semaglutide) You have moderate-to-severe obstructive sleep apnea with obesity (Zepbound is the only FDA-approved pharmacotherapy) You plateaued on semaglutide after 12+ months You have MASH and need the drug with the strongest resolution data (SYNERGY-NASH: 44 to 62% resolution) Your insurance covers Zepbound or Mounjaro You tolerated the 2.5 mg starting dose well during a prior trial Lean semaglutide when: You have established cardiovascular disease or high CV risk

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Taking advantage of small molecules selected from a high-throughput screen and using X-ray crystallography, functional assays, and docking studies, we identify a critical secondary site of the enzyme