GLP-1 receptor agonists cost lean mass but showed no effect on bone or joints

The edition in brief

A meta-analysis of 46 randomised trials and 14 real-world studies covering 1.25 million people found GLP-1 receptor agonists were associated with a consistent fall in lean or fat-free mass, mainly with semaglutide and liraglutide, but no effect on bone density, fractures or osteoarthritis pain and function; certainty was low and the lean mass change appeared largely proportional to weight lost. In healthy volunteers, clarithromycin increased exposure to the CYP3A4-metabolised PDE5 inhibitor aildenafil 2.6-fold, rifampicin cut it by about 99%, and cimetidine had little effect. A pharmacokinetic case study of severe caffeine poisoning showed saturable elimination, with the apparent half-life falling from 42.6 to 11.2 hours as levels fell, and simulations predicting days of toxic exposure at high starting concentrations. The FDA recorded a supplement to Eli Lilly's tirzepatide (Zepbound) application on 12 October; the listing does not state what it changes.