Round 12 Open Questions
Answered this round
- NHS patient experience (UK, HealthUnlocked): ✓ UK T2D patients report dramatic weight loss and HbA1c normalisation; access remains key barrier — NICE TA924 (T2D) since 2023 but GP knowledge patchy; obesity pathway very slow (12-year rollout); notable emerging signal: levothyroxine interaction (possible altered absorption)
- GIP receptor mechanism vs GLP-1 alone: ✓ Three distinct GIPR mechanisms: (1) adipose lipolysis + WAT insulin sensitisation (weight-independent); (2) sustained beta-cell stimulation without tachyphylaxis; (3) lipid/BCAA normalisation — collectively explain tirzepatide’s superiority over semaglutide beyond just additive incretin action
Still unanswered
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Long-term T2D outcomes beyond 2 years: SURPASS trials are 52–104 weeks. Is there data beyond 2 years on T2D outcomes — sustained HbA1c, weight, eGFR, CV events? Do benefits persist with continuous use?
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Real-world outcomes vs trial populations: Do registry or observational studies show the same magnitude of benefit seen in highly selected SURPASS trial populations? Particularly in patients ≥70 years, eGFR variability, multiple comorbidities.
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Pancreatitis risk — absolute rates: The FDA label mentions pancreatitis as an adverse event. What are the absolute incidence rates across SURPASS trials? How does this compare to GLP-1 RA class risk and background T2D pancreatitis rates?
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Drug interactions in complex T2D patients: Levothyroxine interaction emerging from patient reports. Any pharmacokinetic interaction data for warfarin, immunosuppressants, or other high-risk medications commonly used in older T2D patients?
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Cost-effectiveness modelling for NHS T2D (beyond TA924): NICE TA924 established cost-effectiveness for T2D at restricted criteria. With the obesity NICE decision (December 2024) and expanding evidence base (SUMMIT, SURPASS-CVOT), is there updated health economic modelling?