Expert: Semaglutide Versus Tirzepatide, How Both Can Aid Type 2 Diabetes and Obesity

Pharmacy Times interviewed Jennifer N. Clements PharmD, BCACP, BC-ADM, BCPS, CDCES, FADCES, FCCP, a Clinical Professor and Director of Pharmacy Education with the University of South Carolina College of Pharmacy at the School of Medicine, on the role of Semaglutide and Tirzepatide for type 2 diabetes and obesity. Clements discussed treatment recommendations based on the American Diabetes Association Standards of Care and emphasized the need of shared decision making with the patient to find which treatment would be most successful. Clements noted that the drugs have differences and similarities, but both are great choices to aid the conditions.

Pharmacy Times

Can you introduce yourself?

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Jennifer Clements

My name is Jennifer Clements. I am Clinical Professor and Director of Pharmacy Education with the University of South Carolina College of Pharmacy.

Pharmacy Times

Can you give a brief overview on the main differences of Semaglutide and Tirzepatide?

Jennifer Clements

When we look at these two drugs, there are similarities, but then there are also some differences. First, we must look at the pharmacology. We know with Semaglutide being a GLP-1 receptor agonists, it has a unique mechanism as with other drugs in that class, but also hits one gastrointestinal hormone— the GLP-1. With its mechanism, we know diabetes can promote insulin release, suppress glucagon, promote satiety by hitting the receptors in our appetite center in the brain, but then also slow gastric emptying. With Tirzepatide, while there are similarities in terms of being an injectable — having very similar adverse events, being a once weekly, whereas Semaglutide is also once weekly. The main difference that we tend to talk about is that it has this dual mechanism because it is a dual incretin mimetic, as we call it, but then being very specific, a GLP-1 and GIP receptor agonist. That dual effect on two different gastrointestinal hormones is emphasized in terms of potentially being one to cause more weight loss from the studies that it has available and labeled in its packaging.

Pharmacy Times

What are the main treatment recommendations for individuals with type 2 diabetes and obesity?

Jennifer Clements

We can look at two different organizations for where these drugs are really recommended for people with type 2 diabetes and living with obesity. If we look at just obesity by itself, there is obviously the need to update more regularly. In terms of recommendations and algorithms, we see more updates when we look at diabetes. For example, we know that the American Diabetes Association comes out with their standards of care every year, and it is a living document— things can get changed during the year. If we look at type 2 diabetes and obesity, from the American Diabetes Association, we see that both drugs are labeled as having very high efficacy to promote glucose lowering effects, as well as promoting weight loss. There is obviously now in the pathway for treating type 2 diabetes, two different ways to look at it because of cardio renal benefits with certain drugs, then also focusing on glucose, or weight loss. So, that is really where they fall. Of course, we could focus on the other pathway with Cardiorenal benefits, because some GLP-1 receptor agonists do have that in its label. Tirzepatide would have studies coming out in the future to investigate its effect on cardiovascular risk reduction. If you look at the endocrinology guidelines — the American Association of Clinical Endocrinology, very similar in terms of recommending them because of minimum risk of hypoglycemia, but very potent and very efficacious in terms of AIC lowering, but then also promoting weight loss.

Pharmacy Times

What are the benefits, risks, and barriers of both treatments?

Jennifer Clements

I think this is one where a lot of us would have agreement, and maybe it depends on where you practice. Not necessarily a disagreement, but just knowing that where we live and what insurances may cover could vary and depending on our patient population as well. We know with both drugs, they are very beneficial for those with type 2 diabetes and obesity as previously mentioned, but I think because of these two, we see larger and sustained weight loss that we have not seen before in clinical trials. The weight loss is not as large in those with type 2 diabetes, but that is traditionally the trend that we see. But the larger and sustained weight loss is great because we are getting closer and closer to what we see with bariatric surgery because of these new drugs like Semaglutide and now Tirzepatide. With that there are some risks that we must talk about because of their mechanism —there can be nausea and vomiting. With that, you tend to see more of it when you start the drug or anytime you must titrate. They both are once a week; you must start at a lower dose and titrate every month to try to get to the high dose. Semaglutide is 2 — if you look at Ozempic, or 2.4, as Wegovy and then 15 mg with Tirzepatide. I think you must evaluate tolerability before going up or give them education on how to mitigate the nausea and the vomiting that they may be experiencing. There are various ways to help relieve that, such as avoiding certain types of spicy, greasy, or fatty foods, maybe cutting down the portions even more — which may naturally happen when being on one of these drugs, but also maybe what they drink. Avoiding certain types of beverages like carbonated beverages, because that could make you feel a nauseous or just a different way, depending on how that individual reacts. I think barriers that is going come up is cost and coverage from payers, maybe even employee plans, depending on where individuals practice. We also know that people have been dealing with compounded incretins. That has been available because people are seeking these medications out, given various reasons and it has caused a shortage that has waxed and waned over time —then led to alternative ways to get the product, also at a cheaper price. That is a barrier because for us as pharmacists, we know what was studied and then we hear about the compound, and we must address those questions. We are the source of information, but then it also affects the supply because these products are in high demand. That is something that will be a barrier for a while and probably wax and wane over time.

Pharmacy Times

How should health-care providers determine which treatment would better improve the patients’ health?

Jennifer Clements

A strategy is giving the individual all the options that are available because ultimately, they need to be successful. If they have more buy in through shared decision making, then they are more likely to go with something that they believe will make them successful. I do think when having those discussions, it is important to understand that those products are even covered by their insurance, depending on where someone practices. It is an easier conversation with the ability to answer questions about potential cost, when providing them all the options and already knowing what is going to be covered on their insurance. So, maybe having a list where you practice that is updated regularly— having it at the computer of certain plans and what they cover that may change over time because of new evidence, or what comes out with both products. But I think something like that could easily be able to then guide someone in having that conversation because people are going to hear about this, they are going to read it magazine articles, sees the advertisements on TV, talk to their friends — people are going to be aware of it. But the biggest thing that they are going to ask is how much does it cost, does my insurance cover it. If someone is in a transition of care system, or maybe it is something you could recommend at discharge because you see value in it. I have done various things— you could run a dummy script to know the cost or the copay that someone would have. You can think of ways to be creative in how you can ensure that you have all the information before providing the option to the individual, but health care providers and teams are going to want to turn to Semaglutide and Tirzepatide because of their efficacy and what they see in clinical practice and have read from the trials. These are very efficacious medications, as mentioned for AIC lowering and weight loss, and they are highly recommended in the guidelines for those reasons. Health care providers and teams are going to be turning to them if they have not already, which I suspect that most people are going to them, based on what we have seen in terms of trends in practice.

Pharmacy Times

Is there anything else you would like to add?

Jennifer Clements

There are obviously some differences between these drugs and there are even some head-to-head studies with them together — people can go in read those. But again, what we have are two great options. We want to provide the individual with both and if one does not work, it is nice to know you have something else to turn to. You may have your own way of using them in practice, like an algorithm, but I think that both are great choices, and now both having indications for type 2 diabetes, and separate products for obesity. And we look forward to the additional studies that will come out with Tirzepatide, particularly in knowing its potential benefit with cardiovascular endpoints.