Over the weekend, Novo Nordisk dropped a pile of scientific data on three new experimental weight-loss drugs, including an oral one, showing what appears to be a strategic “something for everyone” plan of attack from the pharmaceutical giant.
Weight loss therapeutics is a lucrative market and one that has now landed Novo Nordisk DKK65.1 billion, or more than US$10 billion, in profits – with nearly half of this from 2024 alone. But the makers of Ozempic and Wegovy have plenty of competition, including a new dark horse from China we recently reported on, made by rising pharma company Sciwind.
This weekend, the company released the results of three clinical trials, in the process giving away an interesting new strategy – to not just provide medication for clinical obesity, but offer easier-to-take options for both post-injection “maintenance” and for people who have a more modest amount of “excess weight” they’d like to shift.
So, to keep it as simple as possible, we’ll run through the three – two of which are related but have significant differences in terms of target market.
1. CagriSema
This drug’s timeline has been rocky for Novo Nordisk; early trial data published in February resulted in a $125 billion dip in share value and the eventual ousting of its CEO. But the full, comprehensive trial data is now out, and – at least on paper – it is shaping up as the likely successor to Ozempic and Wegovy.
CagriSema is, as the name hints, semaglutide but more – it combines the GLP-1 receptor agonist with a long-acting amylin analog, caggrilintide. Cagrilintide binds to the calcitonin receptor and all three amylin receptors, essentially silencing hunger and boosting satiety that reduces food intake.
Focusing solely on the results of the Phase IIIa REDEFINE 1 obesity trial, CagriSema achieved the highest weight loss recorded so far in trials. After 68 weeks, 3,417 overweight or obese participants lost an average of 20.4% of their body weight. Breaking the figures down, almost 20% of participants lost 30% or more of their body weight, while nearly two thirds of the people enrolled lost more than 20%. This far outperforms semaglutide on its own over 68 weeks (which has a mean of around 15% of body weight lost).
What’s more, CagriSema performed slightly better in fat loss versus muscle loss, with around 2-7% more fat loss (so 2-7% less muscle loss) than semaglutide alone.
The main difference between this and Wegovy or Ozempic is that it doesn’t just target the GLP-1 receptor to boost insulin and reduce appetite and stomach emptying, it has an equal dose of the amylin analog (cagrilintide), which affects the brain’s satiety signals and boosts appetite suppression.
“In REDEFINE 1, CagriSema provided weight loss in the highest range of efficacy observed with existing weight loss interventions,” said lead investigator Timothy Garvey, MD, a professor at the University of Alabama at Birmingham. “Investigators were allowed some flexibility in dose adjustments to balance efficacy and safety, but regardless of dose adjustments participants lost significant weight. These findings are relatable to clinical practice, where dosing is often adjusted based on individual needs and clinical judgement.”
Discontinuation in the trial was reasonably low at 6%, with reported mild to moderate side effects in line with the gastrointestinal issues also seen in people taking semaglutide. The reasons for quitting the trial were nausea (55%), constipation (30.7%) and vomiting (26.1%), and overall side effects were “mostly transient.”
Novo Nordisk will now make a case for its release, as a once-weekly subcutaneous injectable, and if approved it is likely to see the light of day in 2026.
2. Amycretin
Within a day of the CagriSema news, the drugmaker released the findings of two trials involving the experimental weight-loss drug amycretin, which is expected to reach the market in daily oral and weekly subcutaneous injectable form.
Firstly, a phase Ib/IIa 36-week clinical trial of 125 adults aged 18-55 years and with a BMI of 27-39.9 kg/m² (at the high end of overweight through to severely obese) passed efficacy and safety checkpoints and will move straight onto a Phase III larger trial.
Unlike the semaglutide-cagrilintide combo, amycretin is a single-molecule drug that activates both the amylin and GLP-1 receptors. Like CagriSema, it’s designed to do what semaglutide does, but enhance satiety and and promote fullness to regulate hunger and metabolism better than a GLP-1 receptor agonist alone.
The trial tested dose tolerance and maintenance treatments (20 mg/week). Overall, a 20-mg dose resulted in an average weight loss of 13.1% over 36 weeks. A subgroup were titrated up to 60 mg/week, and the scientists report “up to 24.3%” weight loss, but no average was detailed; this 60-mg subset of participants was primarily testing the drug’s safety and tolerability. And 70% of these participants experienced mild or moderate gastrointestinal issues, including nausea or vomiting, though for most the side effects resolved over time.
In another, separate Phase I trial of amycretin, a daily oral dose was tested on 144 participants (BMI of 25–39.9 kg/m²) over 12 weeks. Those on the highest dose (100 mg/day) lost an average of 5.3% of their body weight after the three months, and as with the weekly injections, the high dose resulted in common gastrointestinal side effects but were reported as manageable.
Because this was the first human trial for oral amycretin, the researchers were testing for a number of factors and focused more on titrating and the tolerability of different combinations of doses. It too will advance to a Phase III trial that more rigorously studies its weight-loss capabilities longer term.
While it’s so far less impactful than existing and experimental injectable therapeutics, a daily pill has obvious advantages – it’s easier, doesn’t require the same cold storage, offers flexibility and is likely to appeal to people who would be considered clinically overweight but not obese.
“We are pleased with the promising results of amycretin and the feedback from regulatory authorities and are excited to advance both subcutaneous and oral versions of this molecule into Phase III development for weight management,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “We understand that addressing obesity is a complex challenge that many patients face. These results reflect our robust pipeline in obesity, our focus on progressing scientific innovation and expanding the range of options available to patients and healthcare professionals.”
The CagriSema study was published in The New England Journal of Medicine; while the amycretin (injected and oral) research was published across two papers in the journal The Lancet.
Source: Novo Nordisk via Scimex
