Cagrilintide
(AM833)

1987-2005

The Forgotten Hormone

Discovering Amylin

In 1987, scientists discovered amylin — a hormone released alongside insulin from the pancreas after meals. It slowed stomach emptying, reduced appetite, and signaled fullness to the brain. Amylin was part of the body's natural meal-ending system.

In diabetes, amylin function was impaired. Type 1 diabetics lost it entirely. Type 2 diabetics became resistant to it. This contributed to overeating and weight gain often seen with diabetes.

The FDA approved pramlintide (Symlin) in 2005 for diabetes. It helped somewhat with blood sugar and weight. But it required injections before every meal — too inconvenient for widespread use.

2017-2020

The GLP-1 Explosion

Semaglutide Changes Everything

When semaglutide (Ozempic/Wegovy) achieved 15%+ weight loss in trials, the obesity treatment landscape transformed. A weekly injection could produce meaningful, sustained weight loss. The medication went viral.

But Novo Nordisk wasn't done. They knew GLP-1 was only part of the satiety system. What if they could target amylin too? The challenge was making an amylin analog that worked with weekly dosing instead of before every meal.

Cagrilintide was born — a modified amylin with a fatty acid chain (like semaglutide) that let it last a full week. One injection could provide continuous amylin signaling.

2020-2023

Better Together

CagriSema Phase II

Novo Nordisk tested cagrilintide alone and with semaglutide. The combination — dubbed CagriSema — produced remarkable results. Phase II trials showed ~15.6% weight loss with the combination, versus just 5.1% with semaglutide alone at the same doses used.

The synergy made biological sense. GLP-1 (semaglutide) and amylin (cagrilintide) work through different pathways and receptors. Together, they created a more complete satiety signal than either alone.

Early data suggested CagriSema might eventually achieve weight loss approaching 25% — territory previously reserved for bariatric surgery.

2023-2025

REDEFINE Trials

Phase III Success

The REDEFINE program launched — large Phase III trials testing CagriSema against semaglutide alone and placebo. The results, announced in late 2024, exceeded expectations.

REDEFINE 1 showed CagriSema achieved approximately 22% weight loss at 68 weeks — significantly more than semaglutide alone. Over 90% of participants lost at least 5% of body weight. The combination was working.

Side effects were similar to other GLP-1 drugs: nausea, vomiting, diarrhea. These typically improved over time. The safety profile supported moving toward approval.

2025-Future

The Next Generation

Beyond Semaglutide Alone

In December 2025, Novo Nordisk filed for FDA approval of CagriSema. If approved, it would become the most effective injectable weight loss treatment available — pushing toward weight loss levels that previously required surgery.

Cagrilintide is also being tested alone for patients who can't tolerate GLP-1 drugs. The amylin-only approach achieved ~12% weight loss in trials — meaningful for those with GLP-1 side effects.

The obesity treatment landscape is rapidly evolving. CagriSema represents the next wave: combination therapies that target multiple satiety pathways simultaneously. The question is no longer whether medications can treat obesity effectively, but how effectively we can do it.