No excess malformation risk with first-trimester benzodiazepines in 4.2 million pregnancies, and lean fatty liver is not a milder prognosis

The edition in brief

A US cohort of about 4.2 million pregnancies in two insurance databases found no increase in major congenital malformations after first-trimester benzodiazepine fills: adjusted absolute risks were 4.0% vs 4.1% (Medicaid) and 4.9% vs 4.8% (commercial), pooled RR 0.99 (95% CI 0.96 to 1.03), with no dose-response; co-exposure analyses were inconsistent. A VA/DoD guideline synopsis on tobacco treatment makes 32 recommendations, including strong ones for motivational interviewing, varenicline over other single agents and combination nicotine replacement over a single product. In SYNCHRONIZE-2, a phase 3 trial of 752 adults with obesity and type 2 diabetes, weekly survodutide 3.6 mg or 6.0 mg lowered weight by 8.2% and 9.8% against 3.9% with placebo at 76 weeks, with gastrointestinal adverse events in about three quarters of treated participants. The drug is investigational and the trial was industry funded. A retrospective study of 18,326 adults with biopsy-confirmed MASLD found that lean patients (6.7% by BMI) had milder histology but similar outcomes after adjustment (all-cause mortality aHR 0.90, 95% CI 0.69 to 1.16), that fibrosis stage drove prognosis (advanced fibrosis aHR 2.10 for mortality), and that elastography performed better than FIB-4 in lean patients. The pearl covers checking for pregnancy before prescribing in women of childbearing age.