The pitch: add amylin to go further
GLP-1s are not getting pushed off the stage. They are getting a co star. Drugmakers are leaning into the amylin pathway to complement existing obesity and diabetes drugs, or to open doors for people who do not get enough benefit from GLP-1s.
That showed up in Lilly's latest data. The company tested eloralintide, an amylin analog, alongside tirzepatide in people living with obesity and Type 2 diabetes. After 48 weeks, the highest dose combo group shed an average 23.3% of body weight, compared with 14.8% for those on a high dose of tirzepatide alone, based on an analysis that counts people as remaining on treatment.
"These are encouraging results," said Benjamin Bikman, a Brigham Young University professor and recognized authority on metabolic health and insulin resistance. He noted that adults with Type 2 diabetes tend to lose less weight on these medicines than those without diabetes.
Safety, staying power, and what comes next
The trial was small, so Lilly still has to prove it at scale. Phase 3 studies are slated to start later this year, and the company says it wants to smooth out tolerability for the combo. In the Phase 2 study, discontinuations due to side effects ranged from 10.8% to 27% for people on both drugs, depending on dose, versus 2.9% for tirzepatide alone. "A therapy is only effective if patients can remain on it, so tolerability in Phase 3 will be as important as efficacy," Bikman said. Dr. Caroline Apovian added, "27% is not a good number."
"Patients may not get what they need from a drug like tirzepatide," said Ken Custer, president of Lilly Cardiometabolic Health. "They may not get what they need from a drug like a eloralintide on its own." Bikman also pointed to the combo as a way to help patients who started on tirzepatide and then hit a plateau.
Why amylin, and how Novo fits in
Amylin is a hormone released with insulin that helps dial down hunger and boost satiety, slowing how quickly the stomach empties. It aims for similar outcomes as GLP-1 drugs, but through a different biological route. The thesis is simple: hit multiple pathways and you might get deeper weight loss or broader metabolic gains than pushing one target ever harder.
Novo Nordisk has been on this road for years. Its amylin analog cagrilintide delivered meaningful weight loss on its own in late stage testing, and pairing it with semaglutide as CagriSema lifted results further in clinical studies. Novo says CagriSema is expected to arrive early next year, with a solo cagrilintide and a higher dose CagriSema planned for 2028.
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Fresh this week, Novo also highlighted that in a yearlong functional MRI study, CagriSema lowered "food noise" and showed improvements in organ and bone health. The company reported that CagriSema changed how the brain responded to high calorie foods in regions tied to cravings, reward and self control among people who were overweight or had obesity. Novo's chief scientific officer, Martin Holst Lange, said, "The signal in the brain changes in a way that actually is associated with improved quality of life."
Novo is advancing another candidate, amycretin, also called zenagamtide, a single molecule designed to hit both GLP-1 and amylin. It is being tested as a weekly injection and a daily pill, and delivered encouraging mid stage data earlier this year.
A quick rewind and what it means for your money
The new wave is long acting, so weekly dosing is the goal. More broadly, the playbook is shifting toward multi hormone medicines. Tirzepatide already combines GLP-1 and GIP. Lilly's retatrutide adds glucagon and, in published data, has produced substantial weight reduction as well as decreases in hepatic fat, triglyceride levels, and fasting insulin.
On the commercial side, Leerink Partners analyst David Risinger thinks eloralintide could be a whale. He sees "millions of individuals, potentially over 10 million people," who tried a GLP-1 and did not get there due to efficacy, tolerability or genetics. His model projects that by the close of 2035, eloralintide products could generate $23.2 billion annually, with the standalone debut in 2029 and the combination following in 2030. He also sees more upside in the standalone drug given the large pool of patients who did not succeed on existing GLP-1s.
For regular investors, the takeaway is more choice ahead for people managing obesity and Type 2 diabetes, spanning weekly injections and possibly daily pills. The open question is whether amylin based combos can keep the efficacy edge while staying tolerable enough for people to stick with them. The next few years of trial readouts and launches will tell you if this becomes a durable, patient friendly category or just a flashy add on.
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