Ablation matched its own sham, and a triple agonist took 19% off bodyweight

The edition in brief

PVI-SHAM-AF randomised 262 patients with symptomatic atrial fibrillation 2:1 to catheter ablation or a sham procedure, both blinded. At six months the AFEQT quality-of-life score rose 19.8 points after ablation and 15.7 after sham, a between-group difference of 2.6 points (95% CI -2.7 to 8.0, p=0.36). Ablation did not show superiority. The trial recruited 262 of 1,199 patients invited, so those enrolled were willing to accept a sham, and follow-up was six months with twelve-month data still to come. TRIUMPH-2 randomised 1,152 adults with obesity and type 2 diabetes to retatrutide, a GIP, GLP-1 and glucagon receptor agonist, at 4, 9 or 12 mg weekly, or placebo, for 80 weeks. Weight fell 18.8% on 12 mg against 5.1% on placebo, a difference of -13.8% (95% CI -15.8 to -11.8). Gastrointestinal effects were common, and discontinuation for adverse events reached 12% on 9 mg against 5% on placebo. Hypotension and dysaesthesia were both commoner than placebo. Two phase 3 trials of oveporexton, an oral orexin receptor 2 agonist, in 273 people with narcolepsy type 1 improved mean sleep latency by 14.3 to 19.8 minutes against placebo, and cut weekly cataplexy by 79% to 89%. Adverse events affected 86-89%, mostly urinary frequency and transient insomnia. An Australian trial found supervised physiotherapy after ACL reconstruction beat self-directed exercise at four months by 4.8 KOOS points, with the gap closing by twelve. The 2026 VA/DoD tobacco guideline puts varenicline ahead of other single agents.