Amylin: the next hormone-based weight management medications?

All of the currently available hormone-based weight management medications are based on a hormone called GLP-1, and most of the emerging treatments are too. The trouble is, there are some people who don’t tolerate GLP-1 (usually due to gastrointestinal side effects), or they don’t tolerate a high enough dose to meet their treatment goals, or they are not reaching their treatment goals despite being on a GLP1 medication. I’m super excited to finally see that a different approach that stimulates receptors of a completely different hormone, called amylin, is really gaining momentum. Hot off the presses is a new study of an amylin analog called eloralintide.

Backgrounder: As blogged previously, amylin is a hormone made by our pancreas, which is secreted when we eat. Amylin talks to our brain to tell us that we feel full, and is also believed to act on parts of the brain involved in the wanting and liking of food (the ‘hedonic’ area, see more on this here), thus having a potential impact on emotional eating and food preferences. It slows down the stomach in response to food intake, and also suppresses glucagon after meals.

Eloralintide is a selective amylin receptor agonist, which looks very promising as a weight management medication based on this new phase 2 study. This study was conducted in USA, enrolling 263 people with obesity to receive eloralintide at various doses ranging from 1mg to 9mg weekly as subcutaneous (under the skin) injections, with some starting at a low dose and working their way up, and some starting at a higher dose right from the start. Participants had an average age of 49, BMI of 39, and 78% were female. At 48 weeks, weight loss of up to 20% was seen with the highest doses of eloralintide, and weight was still going down by the end of the study (had not yet plateaued). The most common side effects were gastrointestinal and fatigue. Not suprisingly, those who titrated up slowly from 3mg to 6mg to 9mg (max dose) did better from a GI side effect perspective compared with the groups who started at higher doses (6mg or 9mg).

There are a number of amylin agonists under development, some of which are selective for the amylin receptor like eloralintide, and others which stimulate both amylin and calcitonin receptors (cagrilintide is in the most advanced stage of development; 11.5% weight loss was demostrated at 68 weeks, as blogged previously here). Further studies will help us better understand what impact selective vs dual receptor stimulation may have on efficacy, obesity-related health benefits, and potential side effects; authors of this eloralintide study hypothesize that selectivity for the amylin receptor might provide an enhanced clinical profile. Pramlintide is a selective amylin agonist that has been available in USA for about 20 years for treatment of type 1 or type 2 diabetes, but is fairly weak in terms of glucose lowering and weight loss effect, and is not approved for weight loss.

BOTTOM LINE: Amylin agonists are a promising new group of emerging weight management medications. We will need to learn more not just about weight loss with these treatments, but importantly, potential health benefits. As for GLP1 medications, it seems that gradual titration is important to minimize GI side effects. Once they hopefully reach approval and clinical use, they will be a welcome alternative for people who don’t tolerate GLP1 medications well, or need more weight management benefit in addition to their existing GLP1-based treatment.

Disclaimer: I am/have been an investigator in clinical trials of cagrilintide. I receive honoraria as a continuing medical education speaker and consultant from the makers of eloralintide (Eli Lilly), and cagrilintide (Novo Nordisk).

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