Round 10 Open Questions
Answered this round
- Beta-cell function / diabetes remission: ✓ HOMA2-B improves vs semaglutide; 13-62% achieve HbA1c <5.7% across SURPASS trials; SURPASS-1 mean HbA1c 5.9-6.1%; but glycaemic gains reverse on stopping — pharmacological control, not structural remission
- Comparative effectiveness vs semaglutide 2.4mg (SURMOUNT-5): ✓ Tirzepatide -20.2% vs semaglutide -13.7% at 72 weeks in obesity without T2D; tirzepatide superior; NOTE: obesity-only trial, not T2D-specific
Still unanswered
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Tirzepatide in advanced CKD (eGFR <30): Safety and dosing — does tirzepatide require dose adjustment? What did SURPASS-4 data show for patients with low eGFR? Can tirzepatide be used safely in dialysis patients?
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NHS patient experience (UK, HealthUnlocked): UK-specific patient experience — do older T2D patients on NHS Mounjaro report different experiences vs US users? Access barriers, continuation criteria challenges?
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Obstructive sleep apnoea (OSA) outcomes: SURMOUNT-OSA trial — tirzepatide in obese patients with OSA. Relevant to T2D patients with OSA comorbidity.
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Long-term cardiovascular outcomes (absolute rates): SURPASS-CVOT showed HR 0.92 (NI vs dulaglutide) — but what are the absolute event rates? How many MACE events per 1000 patient-years? Practical number needed to treat?
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Mechanism of GIP receptor action in T2D context: GIP receptor agonism is the key differentiator from GLP-1 RAs. What does tirzepatide’s GIP component specifically add in T2D beyond what GLP-1 alone provides — visceral fat, adipokines, bone effects?