When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.

Maria Teresa Anton, MD

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide…because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Sue Decotiis, MD

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re much more likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.