Just got back from EASL and the survodutide data is genuinely practice-changing. The Phase 2b results showed 83% histological resolution of MASH at the highest dose (6mg), with 52% achieving fibrosis improvement by at least one stage without worsening of NASH. For those unfamiliar, survodutide is a dual GLP-1/glucagon receptor agonist from Boehringer Ingelheim. The glucagon component is the key differentiator here — it drives hepatic lipid oxidation and reduces de novo lipogenesis far more aggressively than GLP-1 alone. Key endpoints at 48 weeks (6mg dose): - MASH resolution without fibrosis worsening: 83.0% - Fibrosis improvement >=1 stage: 52.3% - Relative liver fat reduction (MRI-PDFF): -86.5% - ALT normalization: 76.2% Compare that to resmetirom (the only FDA-approved MASH therapy) at ~30% MASH resolution. We're in a different stratosphere. The GI tolerability was actually better than expected — nausea rates around 28% at 6mg, mostly transient during titration. Weight loss was substantial at ~18% from baseline, which tracks with the glucagon component's thermogenic effects. Any hepatologists here have thoughts on where this fits in the treatment landscape? I'm particularly interested in whether this could challenge liver biopsy as the standard for monitoring given how dramatic the imaging improvements are.

This is extraordinary data. I've been following the MASH space since the pre-resmetirom days and these numbers make everything else look incremental. A few things jump out at me: 1. The 86.5% relative liver fat reduction is basically normalization for most patients. At my center we're seeing baseline MRI-PDFF values of 15-25% in our MASH cohort — an 86% reduction puts most of them well below the 5% threshold for steatosis. 2. The fibrosis improvement at 52% is the real headline. Resmetirom's MAESTRO-NASH showed ~26% fibrosis improvement at 80mg. Survodutide is doubling that. If these numbers hold in Phase 3, we're looking at a drug that could genuinely alter the natural history of MASH progression to cirrhosis. 3. The dual mechanism makes biological sense. GLP-1 handles the metabolic syndrome/insulin resistance component. Glucagon receptor agonism drives hepatic fat oxidation, increases energy expenditure, and reduces amino acid-driven gluconeogenesis. You're attacking MASH from both the metabolic and the hepatocyte level. My concern is long-term glucagon effects on glycemia in diabetic patients. The Phase 2 data showed modest HbA1c increases in some participants at higher glucagon ratios. How did the 6mg dose handle that?

Great breakdown. I presented a poster on our single-center experience with off-label semaglutide for MASH at DDW last year, so I have some real-world comparator data. Our cohort (n=47, all biopsy-confirmed F2-F3 MASH): - Semaglutide 2.4mg x 52 weeks - MASH resolution: ~38% (vs 83% survodutide) - Fibrosis improvement >=1 stage: ~22% (vs 52% survodutide) - MRI-PDFF reduction: ~55% relative (vs 86% survodutide) - ALT normalization: ~51% (vs 76% survodutide) Semaglutide is good. Survodutide looks transformative. The glucagon component is clearly adding something substantial beyond what GLP-1 alone achieves. RE: glycemia concerns — in the Phase 2b, the HbA1c effect was actually net favorable in participants with T2D (mean reduction ~0.6%). The GLP-1 component appears to more than compensate for glucagon's glycemic effects in most patients. There were a handful of cases with mild hyperglycemia that resolved with dose adjustment. The real question for me: can survodutide reverse F3/F4 fibrosis? The Phase 2 enrolled mostly F1-F3. We desperately need data in compensated cirrhosis.

I'm reading this as a patient with biopsy-confirmed F3 MASH, diagnosed in 2022. Currently on resmetirom 80mg which I started 8 months ago. My labs before resmetirom: - ALT: 87 U/L - AST: 62 U/L - GGT: 124 U/L - FibroScan: 12.8 kPa (F3), CAP 348 dB/m - MRI-PDFF: 22.3% My labs now (8 months on resmetirom): - ALT: 44 U/L (improved but not normalized) - AST: 38 U/L - GGT: 78 U/L - FibroScan: 10.1 kPa (borderline F2-F3), CAP 289 dB/m I've seen improvement but it's been modest. When I read about 83% histological resolution with survodutide, I get frustrated that I'm on a drug that might be second-best. Is there any timeline on when survodutide might be available? And could I potentially switch? My hepatologist hasn't mentioned it.

Completely understand your frustration. A few thoughts: 1. Your resmetirom response is actually reasonable for 8 months. ALT has dropped 49%, FibroScan improved from 12.8 to 10.1 kPa. That's meaningful. Remember resmetirom works through a completely different mechanism (thyroid hormone receptor beta agonism) and its effects on fibrosis tend to be slower and more gradual. 2. Survodutide is still in Phase 3 (the SYNCHRONIZE program). The pivotal trials are expected to read out in late 2026/early 2027, with potential FDA approval in 2027-2028 at the earliest. So we're looking at 1.5-2.5 years minimum. 3. In the interim, combination approaches are where many of us are heading. There's a strong rationale for resmetirom + GLP-1RA. Different mechanisms, potentially synergistic. Some of my F3 patients on resmetirom who I've added semaglutide to have shown additional improvements. Ask your hepatologist about this. 4. Your weight and metabolic status matters here too. If you have significant obesity/T2D alongside the MASH, adding a GLP-1 could address the metabolic driver while resmetirom handles the hepatocyte-level fat metabolism. Don't abandon a working therapy for a drug that's years from approval. Optimize what's available now.