Round 13 Open Questions
Answered this round
- Pancreatitis absolute risk: ✓ Not statistically significant elevated in meta-analyses of 17 RCTs (RR 1.29-1.46, all NS); ~10 cases per 4328 patients (<0.3%); amylase/lipase elevated asymptomatically — not equivalent to pancreatitis; gallbladder disease IS elevated (class effect — rapid weight loss triggers gallstones)
- Real-world outcomes in T2D: ✓ Multiple US registry studies (HIRD, academic centre, TriNetX) confirm trial-level HbA1c and weight reductions; GLP-1 RA naïve patients respond most; tirzepatide favoured over semaglutide in propensity-matched T2D real-world data; TriNetX CV/mortality signal (HR 0.54/0.33) likely confounded
Still unanswered
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Long-term outcomes in T2D beyond 2 years: No published data beyond 104 weeks in T2D. Is there evidence of continued HbA1c and weight maintenance, or attenuation of response? SURPASS-CVOT 5-year follow-up data expected in future publications.
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Older T2D patients (≥70 years) — specific evidence: SURPASS trials enrolled adults 18+, but specific outcomes in those ≥70 with frailty, sarcopenia risk, polypharmacy are not well characterised. Any SURPASS subgroup analyses for older patients?
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Drug interactions — levothyroxine and other medications: HealthUnlocked data suggests thyroid hormone dosing may need adjustment. Any formal pharmacokinetic interaction studies? What about warfarin, immunosuppressants, or narrow therapeutic index drugs?
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Stopping tirzepatide — clinical management: SURMOUNT-4 shows glycaemic rebound after stopping in obesity. What is the recommended clinical approach for T2D patients who need to stop tirzepatide (surgery, side effects, supply shortage)? Bridging strategy?
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Tirzepatide and insulin reduction/cessation in T2D: SURPASS-6 shows it can replace basal insulin. Can tirzepatide enable insulin dose reduction or cessation in patients on full basal-bolus regimens? Any data beyond SURPASS-5/6?