Beginning on June 7, tirzepatide (Mounjaro) will be available in US pharmacies, according to an announcement by Eli Lilly and Company.
Announced on the final day of the American Diabetes Association (ADA) 82nd Scientific Sessions, Eli Lilly and Company noted the dual GIP/GLP-1 receptor agonist, which received approval from the US FDA as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, will be made available 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg doses.
Although not in a population with type 2 diabetes, results of the SURMOUNT-1 trial presented at ADA 2022 added to the excitement surrounding the agent. During Endocrinology Network’s on-site coverage of the meeting, we caught up with Juan Frias, MD, medical director of the National Research Institute and principal investigator of the SURPASS-2 trial, to learn more about his perspective on the excitement surrounding tirzepatide and its potential as a treatment for type 2 diabetes. That conversation can be found below.
Tirzepatide: A New Era in Glucose-Lowering
Endocrinology Network: As someone involved in the SURPASS program, what do you think of the reception of tirzepatide as an agent for T2D but also in weight loss after presentation of SURMOUNT-1 at ADA 2022?
Juan Frias, MD: I think it’s very exciting. We were, and still are, involved in the SURPASS program. Although it wasn’t the primary endpoint, a tremendous amount of weight loss was seen in those patients in SURPASS-1, -2, -3, -4, and -5. I wouldn’t say this was unexpected,based on the phase 2 data, but it’s much more difficult for patients with type 2 diabetes to lose weight and, in SURPASS-2, we saw significantly greater weight loss with tirzepatide versus semaglutide at the 1 mg dose. So, based on the phase 2 data, what we saw in phase 3, and going into SURMOUNT-1, I think the results may have been expected, particularly in nondiabetes patients.
I think it’s very exciting to see findings such as in SURMOUNT-1, for example, that patients had had prediabetes and 95% saw greater reversion to normal glucose tolerance. Clearly, there’s a part of this study that’s extending further that will look specifically at patients with prediabetes and what happens, but just to see that I think is very exciting. Even in patients without diabetes, to see the improvements in glycemic control that we’re seeing in HbA1c from either normal HbA1c to 1.5%, reductions and improvement not only in body weight, which was really unsurpassed in these trials, but also in their whole cardiometabolic profile. Be it blood pressure, be it lipids, be it amino transferases of liver health.
So, I think it’s very exciting. I think it’s from a diabetologist perspective, certainly, we’ve shifted so much from being very focused on glucose to really looking at all of the extra glycemic effects and also just how much improvement in body weight affects not only glucose, but also other cardiovascular risk factors.
Endocrinology Network: The only potential barrier to uptake of tirzepatide would seem to be the lack of data from a dedicated outcomes trial. What do you make of this potential hesitancy?
Juan Frias, MD: I understand the hesitancy in certain patient populations. So, certainly, if I’m going to use incretin-based therapy and one of my key focuses or the key rationale for using it in a patient is for cardiovascular protection, I’m going to go with a GLP-1 receptor agonist with proven cardiovascular benefits. So, this will be dulaglutide or semaglutide once-weekly, but many patients are lower cardiovascular risk. I could certainly use a dual agonist like tirzepatide in conjunction with an SGLT2 inhibitor with cardiovascular benefit. So, I actually do see that hesitancy in that very high-risk person who has established atherosclerotic cardiovascular disease.
Based on SURPASS-4 and based on the prespecified meta-analysis that looked at 7 clinical trials in tirzepatide and type 2 diabetes, I think we’ve established that it is safe. In fact, the hazard ratio of MACE was lower, but these were not trials specifically designed for statistical significance and to assess this cardiovascular safety. So, we’ll need to wait for the data from SURPASS-4, which in my understanding will be in 2024. In the meantime, for those patients that the clinicians have who are using a GLP-1 receptor agonist, specifically for cardiovascular risk reduction, it may be best to use a drug that has proven benefit.