Eli Lilly's other new GLP1 - Orforglipron

The GLP1 Receptor Agonist race continues. The market leaders – Novo Nordisk and Eli Lilly – are producing more and varied new GLP1 drugs, which have fascinating new takes on the ways the category of drugs can be used/how they are made.

At GLP1.Guide we're fans of anything that increases the availability and innovation behind these drugs, so we're happy to see the continuing work on Orforglipron, a non-peptide GLP1 that is taken orally.

What is Orforglipron?

Orforglipron is an orally-taken GLP1, similar to Rybelsus – it isn't taken with an injection pen, but rather by simply swallowing a pill.

Unlike Rybelsus, Orforglipron is actually not a peptide which are normally short chains of amino acids. While Orforglipron works the same way – my mimicking the naturally produced GLP1 hormone – it is not a peptide but instead a separate small molecule. Practically, this means that Orforglipron is easier to produce than other GLP1 Receptor Agonist peptides – which means we can hope for lower prices once if supply is more plentiful.

What does the research say about Orforglipron?

Orforglipron has already advanced to Phase 3, and while we have to wait till 2025 for the next major study to conclude, we can look at previously concluded research.

There was some research done comparing Orforglipron, Dulaglutide and placebo:

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study - PubMed

Eli Lilly and Company.

PubMedJuan P Frias

There is another study that tries to compare Orforglipron against only placebo:

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity - PubMed

Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.).

PubMedSean Wharton

We'll go through each study result individually in more detail to figure out what the results can tell us.

Orforglipron vs Placebo vs Dulaglutide

ClinicalTrials.gov

The first study answers the important question – is Orforglipron the same or better than existing GLP1 peptide treatments?

A few points about the study:

• 352 people actually completed the study (569 were screened)
• The group of participants was 59% men and 41% women
• The average age of participants was 58/59 years old
• The average BMI was 35.2kg/m2 (Note that obesity is generally classified as above 30kg/m2)
• Orforglipron caused an increased occurrence of negative side effects, with most of them being gastrointestinal – 61.8% to 88.9% of patients had some negative side effects occur, compared to 56% with Dulaglutide, and oddly enough 61.8% with placebo.
• In 26 weeks, Orforglipron produced a change in mean body weight of -10.1kg, compared to -3.9kg for Dulaglutide and -2.2 for placebo.

Though the study size was small, Orforglipron showed a dramatically positive results in this study – there is a great improvement in weight loss compared to even relatively recent Dulaglutide and much more improvement over Placebo.

The fact that a non-peptide (which is easier to manufacture) can improve on the results for previous solutions is great news.

Orforglipron vs Placebo

ClinicalTrials.gov

While this study was slightly smaller, it afforded a direct comparison between Orforglipron and placebo – a direct comparison.

A few quick points about this study:

• 272 Participants
• Participants who were given Orforglipron were given doses of 12, 24, 36, or 45 mg
• Average BMI was 37.9 kg/m2
• The most common negative side effects reported were gastrointestinal
• After 26 weeks, the average weight lost was -8.6% to -12.6% across Orforglipron dosage groups, compared with -2% for the placebo group
• By 36 weeks 46-75% of participants who received Orforglipron lost at least 10% of their body weight.

This is another great result for Orforglipron – while the study was not quite so long and there is nothing we can glean from what people taking this drug long term might go through, the results are impressive – a comfortable 4-6x improvement in weight loss over what placebo could produce.

Clearly, Orforglipron is at least as good as recent GLP1 Receptor Agonists, and it looks to be even easier to take, cuts down on waste (people are starting to worry about the waste produced by injection pens), and produces great results.

When will Orforglipron be available?

Outside of participating in a study, it is unlikely anyone will be able to purchase or use Orforglipron for quite a while – studies remain to be conducted and FDA approval also needs to be.

The next time we'll hear about Orforglipron making substantial progress is 2025 – and production is sure to be even further out.

As always it's great to see more options enter the GLP1 RA market place, and hopefully increase accessibility, innovation, and scrutiny into the class of drugs.