Tirzepatide: 'Exciting' and Promising in Lowering A1c

Anne L. Peters, MD


May 23, 2022

This transcript has been edited for clarity.

The FDA just approved tirzepatide as the first dual GIP/GLP-1 (glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1) receptor agonist on the market for treating type 2 diabetes.

The indication that it currently has is reducing glucose in patients with type 2 diabetes who are not successful with diet and exercise. It doesn't yet have a cardiovascular outcomes indication, nor does it have a weight loss indication. But those are likely coming in the next few years, depending on the results of their clinical trials.

I've done a video in the past on the SURPASS trials, which were the main trials that they did. I want to remind you that these trials included over 6000 patients and they saw an A1c reduction from baseline of around 1.9% to 2.6% from baseline. And these A1c reductions were greater than that seen with 1 mg of semaglutide and greater than with adequately titrated doses of the long-acting insulins degludec and glargine. Clearly it is a very strong drug in terms of glucose lowering.

We've also seen significant weight loss with tirzepatide, which is greater than the agents it was studied against. I think these data are really exciting, and they're the data that the FDA used to approve the drug.

Of the remaining trials, the most interesting to me will be the outcomes from the SURPASS Cardiovascular Outcomes study which is being done in over 12,000 people. They're comparing tirzepatide to the existing dulaglutide, which is a GLP-1 receptor agonist that actually has a cardiovascular indication. The results from this trial should be out by the end of 2024 and hopefully it will show cardiovascular benefit.

The other series of studies that are being done are the SURMOUNT trials, looking at the role of tirzepatide in weight loss in people without diabetes. The results from this should be available in the spring of 2023.

Tirzepatide will be available on the market soon and it will come in six different dose strengths starting at 2.5 mg, which is not really a clinically effective dose, and increasing up to the maximum dose of 15 mg. The most common side effects to tirzepatide are similar to the gastrointestinal (GI) side effects that we see with GLP-1 receptor agonists.

Even though I know there are a lot of doses, I'm hopeful that having these slow dose titrations will allow us to reduce some of the GI side effects that we're used to seeing as we use these agents.

It's given once weekly, and it will come in the auto-injector pen that Lilly's dulaglutide is available in, so that patients won't have to learn much in terms of how to give a dose of this agent.

It does carry the same black box warning that the GLP-1 receptor agonists have regarding the risk for medullary thyroid carcinoma. It has the same exclusion for people who have a personal or family history of medullary thyroid carcinoma or an emergent syndrome.

I'm really excited about this drug. I think it's going to help a lot of our patients who still struggle with high A1c levels, and in particular those patients who may be on insulin, patients on insulin who have trouble dosing their insulin or adjusting their insulin. Maybe this will be useful in getting them on either simpler insulin regimens or less insulin.

I don't know yet. I haven't played with it in my practice, but I'm hoping to soon. The one caveat to remember is that it does not have the cardiovascular outcomes indication. And when you have patients with type 2 diabetes and known cardiovascular disease, you may want to stay with an agent that does have a cardiovascular benefit, at least until we have the cardiovascular outcomes trial available with tirzepatide.

This has been Dr. Anne Peters. Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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