The full ESSENCE Phase 3 results confirm semaglutide as the first pharmacotherapy to demonstrate MASH resolution in a pivotal trial. NHS tirzepatide prescribing approaches the critical 16-week review milestone, and Eli Lilly confirms the orforglipron EMA submission.

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ESSENCE — Full Phase 3 Results: Semaglutide in MASH

Novo Nordisk published the full 96-week results of the ESSENCE Phase 3 trial in The New England Journal of Medicine today.

Primary endpoints (96 weeks, n=1,800):

• MASH resolution without worsening fibrosis: 63.4% semaglutide vs 18.8% placebo (p<0.001)
• ≥1 stage fibrosis improvement: 36.8% semaglutide vs 22.1% placebo (p<0.001)
• Both co-primary endpoints met

Secondary endpoints:

• ≥2 stage fibrosis improvement: 18.2% semaglutide vs 8.4% placebo
• Cirrhosis development: 2.1% semaglutide vs 4.8% placebo (HR 0.43, 95% CI 0.24–0.78)
• Weight loss: −14.2% semaglutide vs −2.1% placebo

Novo Nordisk has confirmed simultaneous regulatory submissions to the FDA, EMA, and MHRA for a MASH indication.

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NHS Tirzepatide — 10-Week Update

• Cumulative patients: 88,000
• Prescribing rate: 7,500 new patients per week
• 16-week reviews: The first cohort of patients (those who started 1 February) will reach their 16-week review in late May/early June 2026

NHS England notes that approximately 12% of patients have not yet escalated beyond the 2.5 mg starting dose at 10 weeks, and has issued a reminder that dose escalation should be attempted in all patients unless limited by tolerability.

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Orforglipron — EMA Submission Confirmed

Eli Lilly has confirmed the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency for orforglipron for chronic weight management, simultaneously with the ongoing FDA review (PDUFA date August 2026).

An MHRA submission has also been confirmed, with the UK review running in parallel.

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Research Digest

GLP-1 agonists and addiction: A meta-analysis published in Nature Medicine found that GLP-1 receptor agonists are associated with significant reductions in alcohol use disorder (OR 0.61), smoking cessation failure (OR 0.72), and opioid use disorder (OR 0.68) in observational studies.

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This update is prepared for UK healthcare professionals. All prescribing decisions should reference current NICE guidance, the BNF, and individual patient clinical assessment.