Round 3 Open Questions
Answered this round
- NICE UK guidelines: ✓ TA924 — 3rd/4th line NHS; ≥1% HbA1c + ≥3% weight at 6 months continuation criteria
- Stopping effects / treatment dependence: ✓ SURMOUNT-4 (obesity): >25% weight regain in most patients within 1 year; all cardiometabolic benefits reverse; no T2D cessation trial exists
- Gastroparesis / delayed gastric emptying: ✓ Class GLP-1 effect; surgical aspiration risk; FAERS safety comparable to GLP-1 RAs
Still unanswered
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T2D-specific patient feedback (50+, on insulin): Need Reddit r/diabetes, r/diabetes_t2, HealthUnlocked — specifically patients 50+ with long diabetes duration on insulin reporting real-world experience (HbA1c change, insulin dose reduction, side-effect burden, quality of life).
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Retinopathy worsening risk: FDA label warns of rapid glycaemic improvement transiently worsening diabetic retinopathy. FAERS data (PMID 39141075) has retinopathy safety data — absolute rates not yet captured in vault. Relevant for patients with pre-existing diabetic eye disease.
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SURPASS-CVOT results: SURPASS-CVOT trial (tirzepatide vs dulaglutide in T2D with established ASCVD) may have published — PMID 41406444 identified but not fetched. Critical for cardiovascular claims.
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SURPASS-3 dedicated trial note: HbA1c, weight, and insulin dose reduction data vs insulin degludec still need a dedicated trial note.
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Advanced T2D on basal-bolus insulin (high TDD >80U): No specific SURPASS data for patients on full basal-bolus regimens with high total daily insulin. Evidence gap.
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KDIGO 2022 diabetes and CKD guidelines: Specific positioning of tirzepatide in CKD patients — where does it fit relative to SGLT2 inhibitors (empagliflozin, dapagliflozin) which have established kidney outcomes data?
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Muscle mass / lean body composition: DXA body composition data — does tirzepatide preserve lean mass during weight loss? SURMOUNT-1 extension DXA data may exist.