The headliner: Tirzepatide (Mounjaro) vs semaglutide (Ozempic). Who won?
Tirzepatide! A recently completed open-label RCT of over 700 adults with obesity showed that tirzepatide had superior weight loss compared to semaglutide. Specifically, patients randomized to tirzepatide lost 20% of their body weight compared to 14% with semaglutide. Adverse events were common and were generally similar between the two groups. The top 3 adverse events were nausea (43%), constipation (27%), and diarrhea (24%). A key secondary outcome was reduction in systolic BP. Patients who received tirzepatide had a decrease of 10 mmHg compared to 8 mmHg with semaglutide.
The 2nd headliner: Is semaglutide effective for MASH/NASH?
Yes! There have been prior phase 2 trials, and now we have a phase 3 trial that randomized nearly 1200 patients with biopsy-defined metabolic dysfunction-associated steatohepatitis (MASH, previously NASH). It was a double-blind, placebo-controlled trial of patients with stage 2 or 3 fibrosis, and the key exclusion criteria were alcohol use disorder, GFR < 30, or MELD of 3 or higher. Resolution of steatohepatitis after 72 weeks (the primary outcome) occurred in 62% with semaglutide vs 34% with placebo. This feels like a game-changer. Tune in to Rounds Table to learn more.
Hidden gem: Is there a new and exciting treatment for bronchiectasis?
I guess that is a bit subjective, but I’d say yes. Quick reminder: there really aren’t any medications for non-cystic fibrosis bronchiectasis. Second quick reminder: patients with bronchiectasis classically present with chronic cough, recurrent infections, hemoptysis, and their CT typically shows bronchial dilatation, wall thickening, and lack of tapering. This double-blind trial of over 1700 patients with bronchiectasis randomized patients to a DPP-1 inhibitor, called brensocatib (once daily pill), or placebo. The primary outcome was the rate of pulmonary exacerbations. Patients who received bronchiectasis had a 20% lower rate of pulmonary exacerbations compared to placebo. Adverse events included nasopharyngitis, cough, headache, and hyperkeratosis. The drug is not yet on the market. If you want to learn more, tune in here.
The take home points:
[1] Tirzepatide leads to greater weight loss than semaglutide in adults with obesity (20% vs 14%).
[2] Semaglutide is effective for MASH, showing 62% resolution vs 34% with placebo in a phase 3 RCT.
[3] Brensocatib reduces exacerbations in non-CF bronchiectasis by 20%, making it a promising new therapy.