Round 4 Open Questions
Answered this round
- SURPASS-CVOT results: ✓ Published NEJM Dec 2025; HR 0.92 (noninferior, NOT superior vs dulaglutide); 4-point MACE HR 0.88 (significant); all-cause mortality lower
- Reddit T2D patient feedback: ✓ Strongly positive HbA1c/insulin reduction reports; GI side effects main negative; cost/access barrier real; data anecdotal and self-selected
Still unanswered
-
Retinopathy worsening risk: FDA label warns that rapid glycaemic improvement can transiently worsen diabetic retinopathy. FAERS data (PMID 39141075) reportedly includes retinopathy safety — absolute rates not yet captured. Relevant for patients with pre-existing diabetic eye disease.
-
KDIGO 2022 diabetes and CKD guidelines: Positioning of tirzepatide in CKD patients — where does it fit relative to SGLT2 inhibitors (empagliflozin, dapagliflozin) which have established kidney outcomes data? KDIGO recommends SGLT2i first for CKD — where does tirzepatide fit?
-
SURPASS-3 dedicated trial note: Tirzepatide vs insulin degludec; n=1444; 52 weeks; HbA1c and weight data still need a dedicated note.
-
Muscle mass / lean body composition: DXA body composition data — does tirzepatide preserve lean mass during weight loss in T2D specifically? SURMOUNT DXA data exists for obesity; T2D-specific data unclear.
-
Advanced T2D on basal-bolus insulin (TDD >80U): No specific SURPASS data for patients on full basal-bolus regimens with high total daily insulin. Evidence gap for the vault’s target patient group.
-
SURPASS-CVOT renal secondary endpoints: Full renal data from SURPASS-CVOT (eGFR slope, UACR change, CKD progression) not yet extracted — likely reported in supplementary data.