Amylin and GLP-1: the new frontier of gene-based weight loss therapies, between Big Pharma and revolutionary start-ups

A new generation of therapies promises significant results with fewer side effects. While research is revolutionizing obesity treatment, companies like AstraZeneca and Novo Nordisk reveal a rapidly changing market. Meanwhile, two American biotech firms are testing innovative approaches to turn the body’s cells into mini drug factories producing compounds similar to Ozempic. Early results are promising, but the path to human use is still long.

The companies leading this innovation are reporting results that confirm how central this sector has become to global health. Clinically, a new generation of amylin-based drugs promises to overcome previous limitations. Molecules like cagrilintide and combinations like CagriSema show weight losses of 12% and over 20%, approaching the effects of bariatric surgery without the same risks. Pharmaceutical companies are increasingly focusing on complex combinations - including GIP, glucagon, and peptide YY - to counteract the physiological adaptation that reduces the effectiveness of single-hormone treatments.

AstraZeneca, one of the most active groups in amylin agonists, reported an 11% revenue increase in the first nine months of 2025, with the last quarter rising from $14.46 billion to $15.19 billion and a net margin of around 13%. The picture is different for Novo Nordisk: despite an operating profit of 95.9 billion DKK (+5% from 2024), the group lowered its 2025 guidance due to slowing U.S. demand and competition from compounded versions, reducing projected sales growth to 8-14% and launching a restructuring worth 8-9 billion DKK.

The market is becoming more competitive: new combination drugs could reshape leadership and margins. While science pushes the limits of pharmacological weight loss, the sector enters a phase where innovation, production capacity, and cost control will be decisive.

Beneath the Big Pharma market, however, two young U.S. companies - RenBio and Fractyl Health - are experimenting with gene therapies capable of making cells produce a GLP-1 receptor agonist protein, the same mechanism behind drugs like Ozempic. GLP-1 is a natural hormone that regulates satiety and blood sugar. Drugs that mimic it have revolutionized obesity treatment, but they are expensive, require frequent administration, and can cause nausea and fatigue. This has sparked a race to find longer-lasting alternatives with fewer side effects.

RenBio proposes a surprisingly simple method: a plasmid, a “naked” DNA ring in saline solution, is injected into the muscle and delivered into cells via brief electrical pulses. The cells then read these instructions as their own, continuously producing the GLP-1 protein. In mice, the treatment resulted in a stable 15% weight loss for over a year, with improved blood sugar control.

Fractyl Health, on the other hand, uses a more classical gene therapy approach, employing an adeno-associated virus to insert DNA directly into pancreatic cells. Here, GLP-1 production activates only when the cell produces insulin, reducing the risk of overdosing. In tests on mice and pigs, weight decreased by up to 20% in a few weeks, and the animals no longer gained weight even on high-fat diets.

Despite encouraging results, transitioning to humans requires extreme caution: genetically modifying cells can have irreversible effects, and many promising therapies have stalled in the leap from animals to patients. But in a world where ultra-processed food fuels an obesity epidemic, researchers see these strategies as a potential breakthrough: helping the body generate on its own what today only comes from a weekly injection.

Andrea Pelucchi