ADA2023 in San Diego: Watching Tides Roll In

Suddenly at the ADA2023 meeting in San Diego, it seems the tides are rolling in to promise more options than ever before for treating obesity. By tides we mean all those drugs targeting the GLP-1 receptors. GLP-1 is shorthand for glucagon-like peptide 1. Most, but not all of these drugs making a splash in San Diego are also peptides, which is why so many of them have that tide suffix in their names: semaglutide, tirzepatide, cagrilintide, survodutide.

The outlier yesterday was orforglipron. It is not a peptide, but rather a small molecule that’s easier to make and can be given in a tablet form rather than an injection. Nonetheless, it targets the same GLP-1 receptor that all those tides target. In contrast, peptide drugs are much bigger molecules, hard to make in large quantities, and difficult to administer as anything but an injection.

Two Major Publications for Orforglipron

Orforglipron crashed onto scene yesterday with two big publications. First, in the New England Journal of Medicine came the phase 2 results with this drug for treating obesity. Sean Wharton was the lead author on this dose-ranging study of four doses to find the best dose to take into the pivotal phase 3 studies that will open the door for FDA approval. It was also a short-term study – just 36 weeks. Nonetheless, at the highest dose of 45 mg once daily, orforglipron yielded an average of 15 percent weight loss.

Next came a big publication in Lancet for the study of doses in patients with type 2 diabetes. These patients had an average BMI of 35 – solidly in the range of obesity. Weight loss in this group was less, as has been the case in diabetes with every obesity medicine. Weight reduction is harder when a person has diabetes.

The big news here is that we have yet another small molecule in the pipeline that can be given in a tablet with excellent effectiveness for obesity.

A Whole Symposium for Tirzepatide

In a room packed with hundreds of obesity and diabetes scientists, Jamy Ard chaired a session to present the SURMOUNT-2 study of tirzepatide for obesity in persons with type 2 diabetes. The results did not disappoint. The 15 percent weight loss they found in this population is impressive, as ADA VP for Research and Science Marlon Pragnell told the press:

“The data suggest an incremental effect from tirzepatide. This is a step forward for treating people with obesity and type 2 diabetes. It’s a very promising treatment option.”

The full publication of these results in Lancet showed up oddly as a pdf only, which you can find here. No doubt things are busy at Lancet and they’ll get the study up on the journal’s website eventually.

Cagrilintide, Survodutide, and More to Come

The combination of cagrilintide and semaglutide in persons with both obesity and diabetes scored yet another publication in Lancet yesterday. The weight loss seen in this phase 2 study led Caroline Apovian and Marie McDonnell to comment in an editorial published simultaneously that CagriSema “might surpass” the effectiveness of both semaglutide and tirzepatide for obesity and “might equal that of bariatric surgery.”

Oh, and then there were the results with survodutide – 19 percent weight loss – in a phase 2 study of this drug that didn’t even have a name until yesterday. Much more will be coming about this interesting peptide, which targets glucagon receptors as well as GLP-1.

Truly, the progress in research for treating obesity makes us dizzy. Insights on these tides rolling into ADA2023 will take some time to process. But they clearly bring good news about the prospects for people living with obesity.

Click here, here, here, here, and here for the publications in NEJM and Lancet. For further perspective on survodutide, click here.

A storm at Pors-Loubous, photograph by Henri Camus, licensed under CC BY 1.0

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June 24, 2023