Foundayo Coverage and Dual-Agonist Liver Updates
Week Of May 23 - May 29, 2026
Lilly gained PBM coverage for its full obesity portfolio this week, while data from the European Association for the Study of the Liver (EASL) congress put attention on GLP-1/glucagon duals for liver disease. In the Mechanism Explained section, I go into why glucagon’s actions on the liver help with fibrosis. In the Trial Spotlight, I focus on Novo’s early bet that amylin can reach people who have trouble tolerating GLP-1s.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Eli Lilly secures PBM coverage for Zepbound and Foundayo.
Eli Lilly announced that its obesity portfolio, including Zepbound and Foundayo, is now covered by all three of the largest U.S. pharmacy benefit managers (PBMs). CVS Caremark will begin covering Foundayo on June 1 and will broaden access for Zepbound across its template plans by October 1. Eligible patients with commercial insurance may pay as low as $25 a month for either medicine.
Press | Mechanism: GLP-1/GIP (Zepbound) + oral GLP-1 (Foundayo)
Efsubaglutide alfa Phase IIb data supports advancement to Phase III.
Innogen announced that its Phase IIb ENLIGHT study of Efsubaglutide alfa in 200 Chinese overweight and obese adults without diabetes met its primary endpoint. After 18 weeks of treatment, participants achieved weight reductions of 10.58% (QW) and 9.70% (Q2W), along with a 46.9% decrease in liver fat content. The company also reported a 45.3% increase in the muscle-to-fat ratio, with no hypoglycemic events occurring during the trial.
Press | Mechanism: GLP-1 receptor agonist
📰 PRESS
Kailera walks path paved by Lilly in post-IPO ‘catalyst-rich period’
Press | Mechanism: GLP-1/GIP dual agonist
Lilly wins challenge over Noom’s GLP-1 dosing claims.
Press | Mechanism: GLP-1
CordenPharma acquires AmbioPharm to expand GLP-1 manufacturing.
Press | Mechanism: peptide
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
A Plan B for GLP-1 Intolerance: Novo Tests Cagrilintide on Its Own
Novo Nordisk’s new Phase 1 trial of cagrilintide is small, but it sends a strategic signal well out of proportion to its size. The study (NCT07607587) will enroll 114 adults with obesity and no diabetes who share one specific history: they were treated with a GLP-1 drug, stopped because of gastrointestinal side effects, and are not good candidates to start one again. Nausea, vomiting, and constipation are the most common real-world reasons people come off GLP-1 therapy, and a meaningful share of those who start never reach a full dose. By building a trial exclusively around this group, Novo is testing a clear commercial thesis: that an amylin agonist can serve people the incretin wave has not been able to keep on treatment.
The pharmacological rationale is that amylin works through a different route than GLP-1. It signals satiety largely through the area postrema in the brainstem and slows gastric emptying less aggressively, which is the basis for the bet that it can be tolerated where a GLP-1 could not. The clearest indication of Novo’s intent is the trial’s primary endpoint. It is not weight loss, which amylin is already known to deliver, but the percentage of participants who can reach and hold a standard or higher dose over 26 weeks. The question is not how well cagrilintide works, but whether this particular group can stay on it.
A few caveats keep this in perspective. It is Phase 1, not yet recruiting, and built around tolerability rather than efficacy, so meaningful data are a long way off. However, the positioning makes it worth watching. Studying cagrilintide on its own, separate from the CagriSema combination where it usually appears, suggests Novo sees a standalone amylin franchise aimed at a large population that current obesity drugs do not reach.
ClinicalTrials.gov: NCT07607587 (cagrilintide in GLP-1-intolerant adults)
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
The Liver Is Glucagon’s Home Turf: Why GLP-1 / Glucagon Duals Are Posting Fibrosis Wins (Example drugs: Pemvidutide, Zabopegdutide, Survodutide)
This week’s MASH data wave at the EASL 2026 congress is repositioning GLP-1/glucagon dual agonists as liver-focused therapies, a story rooted in the specific action of glucagon. While pure GLP-1 drugs like semaglutide treat metabolic dysfunction-associated steatohepatitis (MASH) largely by driving weight loss (recent work also finds GLP-1 receptors on liver endothelial and immune cells, hinting at a smaller direct effect), the dual-agonist class adds a second hepatic lever that works directly on the fat-storing liver cells themselves. The glucagon component acts on receptors dense in the liver to stimulate fatty acid oxidation, reduce new fat synthesis, and increase energy expenditure. This mechanism directly coaxes liver cells to burn stored fat, an effect distinct from the indirect benefit of systemic weight loss and a key reason these drugs are posting compelling anti-fibrotic signals.
Adding a typically glucose-raising hormone like glucagon to a metabolic drug seems counterintuitive, but the design is elegant. The GLP-1 component simultaneously stimulates insulin secretion, which effectively neutralizes glucagon’s hyperglycemic potential. This lets the drug harness glucagon’s direct fat-burning effects in the liver without elevating blood sugar. Companies deliberately engineer the activity ratio between the two targets; Altimmune’s pemvidutide, for instance, is a balanced 1:1 dual agonist. The strategy is not a fringe bet: survodutide (Boehringer Ingelheim and Zealand) is the most advanced of these duals, already in Phase 3 for MASH, and retatrutide’s triple agonist layers this same glucagon lever on top of GIP.
The EASL readouts provide fresh evidence for this liver-centric mechanism. D&D Pharmatech’s zabopegdutide showed statistically significant fibrosis improvement on 48-week biopsies, with about half of patients on the high dose achieving at least a one-stage improvement without MASH worsening. Altimmune’s pemvidutide demonstrated fibrosis regression at 24 weeks via AI-based digital pathology and showed broad metabolic benefits at 48 weeks, including a nearly 24% drop in triglycerides. MetaVia’s early-phase DA-1726 posted 9.1% weight loss by day 54, with exploratory FibroScan data hinting at early liver improvements.
Still, the path forward requires navigating real trade-offs. The clinical evidence varies in quality, from gold-standard biopsy histology for zabopegdutide, albeit in a small Phase 2, to digital pathology and non-invasive measures for the others. Glucagon’s known risks, like increased heart rate, remain a dose-limiting concern that requires careful management of the agonist ratio. And in a crowded field with approved agents like Rezdiffra and semaglutide, these dual agonists must ultimately prove that their direct hepatic action delivers anti-fibrotic outcomes beyond what weight loss alone can achieve.
ClinicalTrials.gov: NCT05989711 (pemvidutide IMPACT, MASH) | NCT06410924 (zabopegdutide / DD01, MASH) | NCT06632444 (survodutide LIVERAGE Phase 3, MASH)
🆕 NEWLY REGISTERED TRIALS (industry programs from 5 registered in last week)
Cagrilintide Phase 1 investigating its tolerability in patients who previously stopped GLP-1 therapies due to GI side effects (Novo Nordisk, n=114)
[Safety/Tolerability]
Trials: NCT07607587 | Mechanism: Dual amylin/calcitonin receptor agonist
This newsletter compiles publicly available information from press releases, news sources, and trial registries. Not investment advice.
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