Madrigal Pharmaceuticals once again reported an expectations-beating quarter for its THR-β selective agonist Rezdiffra (resmetirom), the first drug approved to treat metabolic dysfunction-associated steatohepatitis (MASH). And while competition is incoming, management projected confidence that the entrance of injectable GLP-1s into the MASH space will only be a net positive for Rezdiffra — and thanks to a licensing deal last month, Madrigal is cooking up its own combination strategy.The drugmaker reported second-quarter revenues for Rezdiffra of $212.8 million, up 55% quarter-over-quarter and blowing past analyst estimates of about $161 million. The beat pushed Madrigal's shares up more than 8% on Tuesday. GLP-1 strategyRezdiffra's status as the only MASH medication, however, could change as early as next year. Madrigal is projecting that Novo Nordisk’s GLP-1 agonist semaglutide — which recently hit its mark in a pivotal MASH study — could be launched for the liver disease in March 2026. For more on GLP-1s in MASH, see – Vital Signs: Tracking the MASH queue for GLP-1 agonists.On an investor call to discuss Madrigal's financial report, CEO Bill Sibold was nonplussed by the looming competition — and predicted it could even be a boon for Rezdiffra. Novo Nordisk's "efforts will raise awareness and drive broader screening, diagnosis and treatment. This will ultimately benefit patients, and we expect it will also benefit both as the foundational therapy and match for first line patients and from the high real world discontinuation rate of semaglutide," Sibold said. And while GLP-1s are widely used for obesity and diabetes, he noted that their low adherence rates might prove a bigger drawback in MASH. "Only approximately 30% of patients with obesity remain on the medicine after one year," Sibold said, referring to semaglutide. "This is especially relevant in MASH, where we're talking about a 72 week efficacy endpoint for a progressive chronic disease like MASH. Providers want a medicine that patients will stay on, and one that they can administer easily without a titration schedule. And that's where Rezdiffra stands out."Tolerability is also key to Madrigal's new combination strategy for Rezdiffra. Last week, the company paid $120 million upfront to license SYH2086, an oral GLP-1 receptor agonist and orforglipron derivative, from Chinese firm CSPC Pharmaceutical. It expects to start a clinical study of the new programme in the first half of next year.According to Sibold, the company has shown that 5% weight loss can increase Rezdiffra's anti-fibrotic effect, and so Madrigal was looking for a candidate that could achieve that level of weight loss without compromising on tolerability."We are looking to develop a chronic therapy for a chronic disease with Rezdiffra as the foundation. We want to optimise the efficacy and tolerability in MASH by balancing the right amount of weight loss from a GLP-1with the fibrosis and lipid reduction of Rezdiffra in a once-daily well-tolerated pill," Sibold said. "We wanted an orforglipron derivative with a favourable stability and pharmacokinetic profile that was amenable to develop as a combination therapy, and of course, an asset that was actionable. We believe that SYH2086 from CSPC Pharma is the right oral GLP-1 asset for our programme. It gives us the opportunity to develop what we believe could become a best-in-disease, well-tolerated oral combination for MASH."More growth driversThe MASH drug is "well on its way to blockbuster status. We can objectively say it stands among the best speciality launches of the last decade," Sibold said on the call. "US Rezdiffra net sales are now annualising at well over $800 million." According to Madrigal, more than 23,000 patients were taking Rezdiffra at the end of the second quarter, an increase of about 6000 compared with the year's first three-month period. FirstWord recently fielded a survey to US physicians that found an urgent need for MASH treatments has been driving the drug's rapid uptake (see – Physician Views Results: Rezdiffra's uptake driven by unmet need, compelling data and diagnostic flexibility).Another source of near-term growth for Rezdiffra could come from its launch in Germany, planned for this half. The European Commission is expected to make a regulatory decision on the drug later this month following a positive recommendation from the Committee for Medicinal Products for Human Use in June. Madrigal is also working towards a label expansion for Rezdiffra into patients with compensated MASH cirrhosis.