Reliant Robin

ADA2023: An Amazing 3-in-1 Obesity Medicine

The last of four big days at ADA2023 brought us astonishing results from three studies of a new obesity medicine, retatrutide. This is the first 3-in-1 metabolic receptor agonist to advance this far in clinical trials as a medicine for obesity or diabetes. Researchers presented phase 2 results for obesity, diabetes, and NAFLD – three studies in all. It takes a lot to have hundreds of scientists break out in applause when a long and exhausting meeting is all but over. But that’s exactly what happened when Ania Jastreboff unveiled the key weight outcomes for the obesity study in this trio of studies.

Results Unlike Anything Ever Seen Before

The reason for the applause is simple. The results are unlike anything we have ever seen before.

The 2007 threshold for an effective obesity medicine was the delivery of at least five percent weight loss in 35 percent or more of patients in a study. In the retatrutide study of people with obesity or overweight, but not diabetes, 100 percent of patients met that threshold. The average weight loss was 24 percent after 48 weeks at the highest dose tested (12 mg weekly). A quarter of these patients lost more than 30 percent of their weight.

These results are stunning.

Effectiveness in Type 2 Diabetes

In the phase 2 study of retatrutide for people with type 2 diabetes, researchers also reported impressive results. At the highest dose tested, the drug reduced HbA1c from a baseline of 8.3 percent to 6.1 after 36 weeks. Notably, 31 percent of these patients achieved an A1c of less than 5.7 percent – representing a normalization of their glucose control.

Furthermore, they achieved an average weight loss of 17 percent. That’s a strong result in patients with pre-existing type 2 diabetes – patients who are typically more resistant to losing weight.

Potential Effectiveness in NAFLD

As if that were not enough, an analysis of patients from the obesity study who also had NAFLD showed noteworthy indications of benefit for reducing liver fat. At the 12 mg dose, more than 90 percent of persons with both NAFLD and obesity achieved normalization of liver fat. Now this was a small subset of patients from the larger study – only 98 in total. So clearly, much more research will be necessary. But these data offer an impressive early signal of potential effectiveness.

Validation for Multi-Receptor Hormone Agonists

Let’s be clear. This is the beginning of a story that will be unfolding for years. It was only two days ago that Matthias Tschöp won the Banting Medal. He won it for pointing to the potential of these multi-receptor hormone agonists. Now we see his work starting to bear fruit with this particular 3-in-1 obesity medicine.

Remember. A dozen other advanced obesity medicines are in clinical development already. Some of them will surely fall away – as lotiglipron did yesterday. But others will come forward. Obesity will be a target for robust innovation (and competition) for years to come. Simply because the unmet medical need is so great.

Click here for the retatrutide obesity study in NEJM, here for the diabetes study in Lancet, and here for a commentary that goes with it. For further perspective, click here, here, and here.

Reliant Robin, photograph by Dietmar Rabich, licensed under CC BY-SA 4.0

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June 27, 2023