Semaglutide, the drug from the Danish pharmaceutical giant Novo Nordisk, was approved under the brand ‘Ozempic’ for the treatment of diabetes in 2017, followed by Wegovy, the obesity version in 2021.
To those of us working in the field of diabesity (see what I did there?), this was no surprise. We had seen the conference presentations and read the papers. What was surprising, however, is how it has leapt into the public consciousness.
Semaglutide, is the latest in the line of analogues of glucagon-like peptide 1, or GLP1, a gut hormone that was originally identified as one of the two ‘incretins’. These send signals to the pancreas to enhance insulin secretion and help to manage blood sugar levels.
undefined
The drug’s main superpower is that it survives far longer in the blood than native GLP1, which only has a half-life of two minutes. Through a once-weekly injection, it provides improvements in diabetes symptoms, primarily through its actions on the pancreas, and also a 15 per cent loss in weight over two years through its action on the brain.
It was this combination of reduced injection frequency (all previous iterations of these drugs were once daily injections) and improved efficacy (surpassing the magical 10 per cent weight loss barrier), turbo-charged by social media, that drove it into the cultural zeitgeist.
Suddenly, there were celebrities using it to lose a little weight to be ‘red-carpet’ ready, and it soon went viral on TikTok. This led to an unprecedented worldwide demand for the drug that surpassed even the manufacturer’s expectations and led to severe supply issues. In fact, Novo Nordisk had to pause its advertisement campaign for a time, such was the severity of the problem.
Read more:
- The carnivore diet: What eating only meat does to your health, a nutritionist explains
- Dr Michael Mosley: The best way to lose weight? Eat more protein
- The 3 rules your diet needs to actually work
The remarkable thing is that the rise of semaglutide was just a prologue. Since then, there have been a series of drugs, either approved or in various phases of clinical trials that, on the face of it, have emerged as superior rivals.
All of these new players share one thing in common; unlike semaglutide, which is a ‘mono-agonist’, that only targets the GLP1 receptor, they target multiple receptors.
Eli Lilly came first with tirzepatide, a drug that targets both the GLP1 and glucose-dependent insulinotropic polypeptide, or GIP, the second incretin.
While also a once-weekly injection, because it targets both incretin receptors, it is, under the brand Mounjaro, more effective at maintaining blood sugar levels, and branded as Zepbound, results in more weight loss (20 per cent) over two years, as compared to semaglutide.
If hitting two receptors is better, what happens when you target three? Eli Lilly asked exactly that question, with their next compound retatrutide, which targets the GLP1, GIP and glucagon receptors.
This approach resulted in an almost 25 per cent weight loss in just 48 weeks.
However, we must keep in mind that these were the results from a phase 2 trial and we wait with bated breath to see the results from the final phase 3 trial.
The newest kid on the block, which takes a very different tack, is AMG133 from AMGEN. As with some of the other drugs we have discussed here, AMG133 targets both the GLP1 and GIP receptors. But uniquely, instead of activating the GIP receptor, they are blocking it with an anti-body.
Without going into the minutiae, there is ample evidence that either blocking or activating the GIP receptor has positive benefits, although no one has any real idea why.
So does it work? Well, AMG133, on a monthly dosing regime, results in 15 per cent weight loss in just three months.
However, it is early days yet – only the phase 1 trial data involving just over 20 participants has been published.
What these approaches have shown us is that the multiple attack approach allows more scope for tailoring treatment, hence increasing efficacy, improving tolerability, and reducing side effects.
However, in addition to diabetes and obesity, semaglutide has additionally been approved as a therapy for heart disease and is being trialled as a treatment for Alzheimer’s disease. It isn’t certain that these other drugs will have the same ‘extracurricular’ benefits - only time will tell.
What I do know is that there has never been a more exciting time to work in the field of obesity, certainly with regard to the number of treatment tools available now. But while useful as treatments, these drugs won’t fix the root cause of the problem. That will require changing policy and tackling poverty.
Read more: