Novel Dual Agonists for Type 2 Diabetes


Drs Dennis Bruemmer and Jennifer Green review recent trial data on a novel combination of GIP and GLP1 receptor agonists to treat type 2 diabetes.

Jennifer B. Green, MD: We should shift to what we see in the future as options to treat and improve the lives of patients with type 2 diabetes. One of the exciting topics at the last ADA [American Diabetes Association] meeting was related to data presented from the tirzepatide trial, which is a novel but not available combination GIP and GLP1 receptor agonist. This has been an interesting concept. There have been a number of agents in development that have had varying effects on GLP1 receptors, GIP receptors, and glucagon receptors, because we know that various degrees of stimulation or inhibition of those receptors can be associated with a wide and complementary way of metabolic benefits.

This agent, tirzepatide, appears to be closest to becoming available for treatment for our patients. The trial data were very exciting to see that use of this combination agent provided outcomes benefits, particularly with respect to weight loss and glycemic control, that appeared to reproduce and exceed those provided by the comparator GLP1 receptor agonist. We’re seeing an option for patients who either need more than effective and available GLP1 receptor agonism, or patients who might already be maxed out on the dose of a GLP1 receptor agonist that they can tolerate, or that’s FDA approved for glycemic control. Perhaps this represents a next step for such patients. We all have patients who are on as many classes as we feel are effective choices for them, but still struggle with glycemic control, weight management, or both. It’s very exciting to have at least 1 such agent on the near horizon. Did you have any other thoughts about the data that were presented?

Dennis Bruemmer, MD, PhD: It’s fair to say that the data were quite powerful if not stunning. If you look at the SURPASS-3 trial data, the hemoglobin A1C [glycated hemoglobin] drop was 2.3% with 1 injection per week compared with degludec. More than 80% of patients achieved hemoglobin A1C of less than 7% in that study. That’s the most powerful drug that will become available. The maximum body-weight reduction was 12.9 kg compared with degludec, which raised the weight by 2 kg. It’s a very powerful medication, with less hypoglycemia, not just because of the comparison with basal insulin but also through the increased glucagon secretion that occurs with the GIP component of the dual incretin molecules. It’s a promising and powerful drug that will expand our tools that we have available.

One of the main challenges that we’re faced with is: how do we apply all these new medications to the broad population? How do we make this available? You mentioned that we need to be proactive in our care. That will be the main challenge: going from socioeconomics to formulary restrictions to access to patients to physicians and nurses. There’s a lot to be discussed and to be done, but it’s certainly a powerful medication.

Jennifer B. Green, MD: What we may see over time is a shake-up in the traditional stepwise approach to diabetes care, where you add 1 drug and essentially wait for it to fail before another is added. Perhaps we’ll be able to treat diabetes a little differently if we can choose very effective agents from the outset. Certainly, the GRADE trial results weren’t encouraging regarding long-term effectiveness of available agents, but we can talk about that further. That trial probably has much more interesting information to come.

Thank you, Dr Bruemmer. I’d like to thank everyone for watching this HCPLive® Peers & Perspectives®. If you enjoyed the content, please subscribe to the e-newsletters to receive upcoming Peers & Perspectives® and other great content right in your in-box. Thank you very much.

Transcript edited for clarity.

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