Round 5 Open Questions
Answered this round
- Retinopathy worsening risk: ✓ Nuanced picture — worsening in moderate-severe NPDR (OR 2.15); protective in patients without retinopathy (OR 0.73); overall better than GLP-1 RA in large EHR study
- SURPASS-3 dedicated trial note: ✓ Tirzepatide vs insulin degludec, n=1444, 52wks; HbA1c −1.93/−2.20/−2.37% vs −1.34%; weight −7.5 to −12.9 kg vs +2.3 kg; hypoglycaemia 1–2% vs 7%
Still unanswered
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KDIGO 2022 diabetes and CKD guidelines: Positioning of tirzepatide in CKD patients — where does it fit relative to SGLT2 inhibitors with established kidney outcomes trial data? KDIGO 2022 was published before tirzepatide’s major kidney data; what does it say?
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Muscle mass / lean body composition: DXA body composition data — does tirzepatide preserve lean mass during weight loss in T2D specifically? SURMOUNT trials used DXA but enrolled obesity not T2D. What is the lean mass impact for T2D patients who lose 10–15% body weight?
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Advanced T2D on basal-bolus insulin (TDD >80U): No specific SURPASS data. SURPASS-6 covers basal insulin users; SURPASS-3 covers insulin-naive. What happens to patients already on full basal-bolus regimens? Clinical guidance and real-world experience?
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EASD 2022 position statement and AACE 2023 guidelines: Positioning of tirzepatide relative to SGLT2 inhibitors and GLP-1 RAs in European and American endocrinological society guidance.
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Liver disease (MASLD/NAFLD) outcomes: SURPASS-3 MRI substudy shows liver fat reduction; any dedicated MASLD outcomes evidence? Tirzepatide in NASH trials?