The buzz and excitement in the world of weight loss medications is previously unsurpassed, with the advent of semaglutide (Wegovy for weight loss, also known as Ozempic for type 2 diabetes), and tirzepatide (approved as Mounjaro for type 2 diabetes, not yet approved as a weight loss medication).
Many people are enjoying the benefits of these treatments, to improve health and weight.
But what is missing from these exciting treatment options?
Both semaglutide and tirzepatide are GLP1 receptor agonists (GLP1RAs). GLP1 is a hormone that our intestines make when we eat, which works at the pancreas to help control blood sugar for people with diabetes or prediabetes, and works in the brain to reduce appetite, and can also reduce cravings for some people. Tirzepatide is also a GIP receptor agonist (thus it is called a dual GIP/GLP1 agonist), which has effects also to control blood sugar and appetite.
Unfortunately, there are some people who do not tolerate GLP1RAs due to gastrointestinal side effects (though these side effects can often be successfully navigated – more on this published in Postgraduate Medicine – disclosure, I am senior author). There are also people who should not be started on GLP1RAs, such as people with an (extremely rare) personal or family history of medullary thyroid cancer.
The main advanced contenders in the obesity medication pipeline also contain GLP1, so these are unlikely to be options for people who have tried but not tolerated other GLP1RAs. Note that regarding these pipeline medications, the jury is not out on the tolerance piece yet – perhaps with the balance of adding other hormone activity to the mix in these upcoming options, there could be better tolerance – but so far the studies do not suggest this.
Just as we have many medication options for other medical conditions like hypertension, we need more obesity medication options that do not contain GLP1. Some exist on the market already, such as naltrexone/bupropion (Contrave), orlistat (Xenical), and phentermine/topiramate (Qsymia – note this is not available in Canada). But we need more choices.
There are some contenders that could fit the bill. For example:
- Cagrilintide, which demonstrated -10.8% weight loss at 26 weeks, compared to -9% with liraglutide 3mg (Saxenda, a GLP1RA) and -3% with placebo (disclosure: I was an investigator and co-author of this paper).
- A GIP receptor agonist has shown promise in a phase 1 trial – and without nausea as a side effect.
- A host of other hormone-based medications are under consideration in early development phases as well.
While the above contenders may not prove to achieve the 20+ percent weight loss that we are seeing with the newer GLP1-based strategies, we need more non-GLP1 based options (in addition to the few already available) to help people who do not tolerate or cannot take GLP1RAs. In our quest for a precision medicine approach to weight management, I hope that the future brings a host of additional medication choices, so that we can find the right treatment for each person.
Disclaimer: I am/have been an investigator in clinical trials of tirzepatide, semaglutide, liraglutide, and cagrilintide. I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide, liraglutide and cagrilintide (Novo Nordisk), tirzepatide (Eli Lilly), and naltrexone/bupropion (Bausch).
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