GLP-1 Oral Meds: Any Drawbacks?

First introduced as a diabetes medication, GLP-1 drugs quickly took hold for off-label use as weight loss aids, even when the science was still very young.

Here’s one of our first articles on that, back in the day: Semaglutide’s Surprisingly Big Research Gap

As for that popularity? Check out: 1 in 5 US Women Aged 50–64 Has Used GLP-1 RAs: What We’ve Learned

Spoiler, one of the things we’ve learned is: Most People Who Start GLP-1 RAs Quit Them Within A Year (Here’s Why)

One of the main things in their favor is, of course, that (for most people, anyway), they work (except when they don’t: Why Intermittent Fasting (& GLP-1 Drugs!) Might Not Work For You).

In other words, a rocky road with pros and cons. But today, let’s talk about the question many have been asking:

Does it come in a pill?

Most people don’t love injections, and GLP-1 drugs being injection-only for these past years has not been simply because the drug companies like to be annoying.

In fact, there are often technical challenges with making a drug work by different routes of administration, for example:

• Skincare products are usually not best taken rectally
• It’s hard to make a gut-repair drug that can be taken as a transdermal skin cream
• And so on

For this reason, subcutaneous injections have worked as a way of delivering drugs to agonize GLP-1 receptors, in ways it’s been hard to do with a pill that has to get past stomach acid and your gut barrier, before getting into your bloodstream.

However! Most recently, researchers (Dr. Vanita Aroda et al.) tested elecoglipron, a once-daily oral GLP-1 receptor agonist for type 2 diabetes, in a sizeable trial involving 406 participants across 9 countries.

Unlike most GLP-1 drugs, elecoglipron is a non-peptide tablet taken once daily with no food or fluid restrictions, making treatment much more convenient.

In numbers:

• Before starting: the average participant was 58.4 years old, weighed 99.8 kg, had a BMI of 34.9 kg/m², and started with an HbA1c of 7.9%.
• Blood sugar results: after 26 weeks, HbA1c fell by 0.91 to 1.88 percentage points depending on dose, compared with a 0.15 percentage-point reduction in the placebo group.
• HbA1c results: up to 89.6% of participants receiving elecoglipron reached an HbA1c of 7% or below, compared with 24.9% of those receiving placebo.
• Weight loss results: up to 72.3% of participants taking elecoglipron lost at least 5% of their body weight, compared with 20.2% in the placebo group.
• Side effects: adverse events occurred in 63% to 87% of participants across the elecoglipron groups versus 63% with placebo, with the most common being nausea, constipation, diarrhoea, and vomiting. This sounds bad, and by itself it is, but it’s worth noting that the drug’s safety and tolerability were generally consistent with other GLP-1 receptor agonists. So in other words, in terms of adverse effects it’s very comparable to Ozempic, Wegovy, Mounjaro, and all the others of that ilk.

In other words: it works! Very comparable to other GLP-1 RAs. Same drug-related drawbacks, just without the needles.

You can find the paper itself, here: Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial

Want to learn more?

You might also like this book that we reviewed a little while back:

Magic Pill: The Extraordinary Benefits and Disturbing Risks of the New Weight-Loss Drugs – by Johann Hari

Take care!