Round 2 Open Questions

Answered this round

  • Gallbladder disease rates: ✓ Composite RR 1.97 (significant); individual components ≤1%
  • Pancreatitis: ✓ Not significantly increased in RCT meta-analyses
  • Discontinuation rates: ✓ 3–10% dose-dependent
  • Guidelines (ADA 2023/2024): ✓ Added; positioned as preferred agent for T2D+obesity
  • Circulation claims: ✓ Classified as “weak” evidence — only indirect biomarker and risk factor data
  • Patient feedback overview: ✓ Drugs.com 8.5/10, ~70% positive; mixed GI tolerance

Still unanswered

  1. T2D-specific patient feedback (50+): Reviews aggregated across T2D and obesity users. Need Reddit r/diabetes and HealthUnlocked T2D threads specifically reporting experience in patients 50+ with long diabetes duration, on insulin.

  2. Gastroparesis and retinopathy risks: FDA label mentions gastroparesis-like symptoms and retinopathy worsening (rapid glucose reduction can transiently worsen diabetic retinopathy). Absolute rates not yet captured.

  3. NICE guidelines (UK) and KDIGO 2022 diabetes and CKD: Specific recommendations for tirzepatide in UK practice and in CKD patients. NICE approved; positioning details missing.

  4. Stopping effects / treatment dependence: What evidence exists for tirzepatide washout? Weight regain and glycaemic rebound after stopping. SURMOUNT-4 washout data for obesity — relevance to T2D unclear.

  5. Advanced T2D on basal-bolus insulin: SURPASS-6 covers basal insulin + tirzepatide vs adding prandial. What about patients on full basal-bolus regimens (high total daily insulin >80U)? No specific SURPASS data.

  6. SURPASS-3 detailed data: HbA1c, weight, and insulin dose reduction data for SURPASS-3 (vs insulin degludec) still need a dedicated trial note.

  7. SURPASS-CVOT results: Trial vs dulaglutide in T2D with established ASCVD — results not yet available in knowledge base.