Seed Round Open Questions
Unanswered after seed research
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Circulation claims: What is the specific evidence (or lack thereof) for tirzepatide “improving blood circulation”? Is this a marketing claim based on indirect CV risk factor reduction (BP, HbA1c, weight), or is there direct vascular evidence (endothelial function, peripheral blood flow)?
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Side effect rates — gallbladder disease and pancreatitis: What are the absolute rates of gallbladder events (cholecystitis, cholelithiasis) and pancreatitis with tirzepatide? These were not captured in search results but are class concerns for GLP-1 RAs and relevant to the FDA label.
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Patient feedback — real-world vs trial: What do patients with T2D specifically report about tirzepatide on Drugs.com, WebMD, Reddit diabetes forums? Particularly regarding: insulin dose reduction in practice, GI tolerability over time, and effects in older adults (60+).
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Long-term dependence and stopping effects: What happens to patients who stop tirzepatide? Evidence for rebound hyperglycaemia, weight regain, and insulin requirement after discontinuation is absent from the SURPASS trials (which had no washout phase).
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Guideline positioning — ADA, EASD, NICE, KDIGO as of 2023–2024: Exactly where do major guidelines position tirzepatide relative to SGLT2i and semaglutide, especially for patients with CKD or cardiovascular disease?
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Advanced T2D — very high insulin doses: The SURPASS-6 population was on basal insulin; the most advanced patients using 80–100+ units/day of total insulin are not well represented. Does tirzepatide work similarly in severe insulin-requiring T2D?
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SURPASS-3 results: Full HbA1c, weight, and insulin dose reduction data from SURPASS-3 (vs insulin degludec) need to be captured in a dedicated trial note.