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Semantic Search: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.896
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z > • > News-Medical coverage: “New quintuple agonist shows promise for treating obesity and type 2 diabetes.” September 21, 2025. news-medical.net > • > Andreassen KV, et al. Research on Dual Amylin and Calcitonin Receptor Agonists (DACRAs, KBP-042, KBP-089) — various publications > • > Eli Lilly pipeline page (no quintuple currently listed): lilly.com/science/research-de
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.896
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z > • > News-Medical coverage: “New quintuple agonist shows promise for treating obesity and type 2 diabetes.” September 21, 2025. news-medical.net > • > Andreassen KV, et al. Research on Dual Amylin and Calcitonin Receptor Agonists (DACRAs, KBP-042, KBP-089) — various publications > • > Eli Lilly pipeline page (no quintuple currently listed): lilly.com/science/research-de
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.891
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z of the next 12-18 months. The quintuple is the story of the early 2030s at the earliest. Many preclinical compounds never make it to humans. The history of drug development is full of animal models that looked amazing and then failed in translation. We should expect that possibility with any new molecule. The dysesthesia signal in retatrutide — the abnormal sensation s
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.891
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z View this post on the web at https://derekpruski.substack.com/p/eli-lillys-quintuple-agonist-the Let’s talk about one of the biggest stories currently brewing in the obesity and metabolic disease space — Eli Lilly’s rumored quintuple agonist. If you’ve been on peptide Twitter, Reddit, or Instagram the last few weeks, you’ve seen the hype. Animal data reportedly droppin
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.880
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z still mouse data Mouse-to-market is typically 8-12 years Retatrutide is what’s actually arriving soon Eloralintide is what’s actually advancing through Phase 3 for amylin The quintuple, if real, is a late-decade story The most important thing to do right now is stay curious and stay patient. Let the science play out. Don’t build expectations around compounds that haven
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.871
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z > Upgrade to paid > I want to walk through what’s actually going on here, because there’s real, exciting science behind this AND there’s a lot of social media buzz that’s getting mashed together. The mechanism is fascinating, the trajectory of the field is remarkable, and calcitonin in particular could solve problems nobody has solved yet. > This post is going to cover w
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.871
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z > Upgrade to paid > I want to walk through what’s actually going on here, because there’s real, exciting science behind this AND there’s a lot of social media buzz that’s getting mashed together. The mechanism is fascinating, the trajectory of the field is remarkable, and calcitonin in particular could solve problems nobody has solved yet. > This post is going to cover w
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.870
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z in human trials — but it demonstrates that pushing past three receptor targets is a legitimate and productive research direction. Different compound, same direction of travel. ═══════════════════════════════ THE CURRENT LANDSCAPE — WHAT’S ACTUALLY IN TRIALS To keep perspective on where the quintuple fits in, here’s what’s actually advancing right now. Retatrutide (Trip
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.866
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z be a quintuple before that is a scam > > ═══════════════════════════════ > BOTTOM LINE > The progression from dual to triple to quintuple is one of the most exciting trajectories in modern metabolic medicine. > What makes the quintuple concept interesting: > > • > Each receptor in the rumored stack solves a distinct problem > • > The mechanisms are complementary, not red
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.866
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z be a quintuple before that is a scam > > ═══════════════════════════════ > BOTTOM LINE > The progression from dual to triple to quintuple is one of the most exciting trajectories in modern metabolic medicine. > What makes the quintuple concept interesting: > > • > Each receptor in the rumored stack solves a distinct problem > • > The mechanisms are complementary, not red
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.859
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z ---------- Forwarded message ---------- From: Derek from Research Radar <derekpruski@substack.com> Date: Apr 24, 2026 at 9:10 AM -0400 To: tjphuhs@gmail.com Subject: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine > Let’s talk about one of the biggest stories currently brewing in the obesity and metabolic disease space — Eli Lilly’s rumored quintup
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.859
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z ---------- Forwarded message ---------- From: Derek from Research Radar <derekpruski@substack.com> Date: Apr 24, 2026 at 9:10 AM -0400 To: tjphuhs@gmail.com Subject: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine > Let’s talk about one of the biggest stories currently brewing in the obesity and metabolic disease space — Eli Lilly’s rumored quintup
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.858
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z single dose and push efficacy into territory that previously only bariatric surgery could reach. ═══════════════════════════════ THE FIVE RECEPTORS AND WHY EACH MATTERS The rumored Lilly quintuple reportedly targets GLP-1, GIP, glucagon, amylin, and calcitonin. Let’s break down what each one actually does. GLP-1 (Glucagon-Like Peptide-1) This is the backbone of every m
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.853
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z control (the tirzepatide backbone) Adding glucagon brings fat-burning and energy expenditure (the retatrutide upgrade) Adding amylin brings extended satiety and slowed gastric emptying from a different pathway Adding calcitonin brings longer-duration satiety, insulin sensitivity, and bone/joint protection On paper, you’d be combining the best of everything that’s alrea
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.845
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z PPAR part is only released inside cells that express GLP-1 or GIP receptors, so it’s targeted rather than systemic. > Mouse models showed it outperformed GLP-1/GIP co-agonism alone on both weight and glucose control. > This is academic preclinical work — not owned by Lilly, not in human trials — but it demonstrates that pushing past three receptor targets is a legitimate
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.845
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z PPAR part is only released inside cells that express GLP-1 or GIP receptors, so it’s targeted rather than systemic. > Mouse models showed it outperformed GLP-1/GIP co-agonism alone on both weight and glucose control. > This is academic preclinical work — not owned by Lilly, not in human trials — but it demonstrates that pushing past three receptor targets is a legitimate
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.839
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z sits well behind all of these. > ═══════════════════════════════ > WHY TIME IS THE KEY VARIABLE > Here’s what matters most for anyone following this story. The excitement is warranted, but the timeline is not short. > If animal data drops at ADA in 5 weeks, that’s mouse data. From mouse preclinical to approved human drug is historically 8-12 years. Even in this accelerat
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.839
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z sits well behind all of these. > ═══════════════════════════════ > WHY TIME IS THE KEY VARIABLE > Here’s what matters most for anyone following this story. The excitement is warranted, but the timeline is not short. > If animal data drops at ADA in 5 weeks, that’s mouse data. From mouse preclinical to approved human drug is historically 8-12 years. Even in this accelerat
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.834
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z actually does. > GLP-1 (Glucagon-Like Peptide-1) > This is the backbone of every modern weight loss drug, from semaglutide forward. GLP-1 stimulates insulin release when blood sugar is high, suppresses glucagon (preventing unnecessary sugar release from the liver), and slows gastric emptying so you feel full longer. It also acts directly on the brain’s appetite centers i
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.834
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z actually does. > GLP-1 (Glucagon-Like Peptide-1) > This is the backbone of every modern weight loss drug, from semaglutide forward. GLP-1 stimulates insulin release when blood sugar is high, suppresses glucagon (preventing unnecessary sugar release from the liver), and slows gastric emptying so you feel full longer. It also acts directly on the brain’s appetite centers i
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.828
· Account tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z and GIP give core appetite and blood sugar control (the tirzepatide backbone) > • > Adding glucagon brings fat-burning and energy expenditure (the retatrutide upgrade) > • > Adding amylin brings extended satiety and slowed gastric emptying from a different pathway > • > Adding calcitonin brings longer-duration satiety, insulin sensitivity, and bone/joint protection > > O
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.828
· Account oc.tjphuhs@gmail.com
· 4/24/2026, 9:42:34 AM
Fwd: Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from tjphuhs@gmail.com on 2026-04-24T13:42:34.000Z and GIP give core appetite and blood sugar control (the tirzepatide backbone) > • > Adding glucagon brings fat-burning and energy expenditure (the retatrutide upgrade) > • > Adding amylin brings extended satiety and slowed gastric emptying from a different pathway > • > Adding calcitonin brings longer-duration satiety, insulin sensitivity, and bone/joint protection > > O
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine
Score 0.796
· Account tjphuhs@gmail.com
· 4/24/2026, 9:05:46 AM
Eli Lilly’s Quintuple Agonist: The Next Frontier in Metabolic Medicine from derekpruski@substack.com on 2026-04-24T13:05:46.000Z have better tolerability than incretins, with less nausea Lilly’s eloralintide (a selective amylin agonist) showed up to 20.1% weight loss at 48 weeks in Phase 2 — as a standalone drug. Novo Nordisk’s CagriSema combines semaglutide with an amylin agonist for this exact reason. Amylin is a proven target. Calcitonin This is the most interesting addition, and the one most
Quintuple Agonist for Obesity: One Drug, 5 Receptors
Score 0.788
· Account tjphuhs@gmail.com
· 4/24/2026, 11:51:08 AM
Quintuple Agonist for Obesity: One Drug, 5 Receptors from onthepen@substack.com on 2026-04-24T15:51:08.000Z frameworks. Biologics introduce a different level of complexity, a different regulatory pathway, and a different set of barriers. A quintuple agonist fits into that shift in a way that is hard to ignore. Increasing the number of pathways is not just about amplifying weight loss, it also increases the complexity of the molecule itself. Complexity makes meaningful replication more difficult,
Quintuple Agonist for Obesity: One Drug, 5 Receptors
Score 0.784
· Account tjphuhs@gmail.com
· 4/24/2026, 11:51:08 AM
Quintuple Agonist for Obesity: One Drug, 5 Receptors from onthepen@substack.com on 2026-04-24T15:51:08.000Z hoping they line up in a way that produces a net benefit. A multi agonist is one engineered molecule with a single pharmacokinetic profile that is designed to engage multiple receptors in a coordinated and predictable way. The ratios are fixed, the timing is unified, and the interaction across receptors is intentional rather than incidental. That is the difference between experimentation a