Marketed for type 2 diabetes as Mounjaro, the drug can lead to dramatic weight loss and a significant reduction in A1C, or average blood sugar levels, in people with type 2 diabetes. Mounjaro is now commercially available for that group, says Maggie Pfeiffer, the associate director of Lilly Diabetes Communications (Eli Lilly and Company manufactures the drug). This once-weekly injection was approved by the FDA as a new class of medication for people with type 2 diabetes on May 13, 2022. On October 6, 2022, Eli Lilly announced in a press release that the FDA had given Fast Track designation to tirzepatide as a potential treatment for people with weight-related health diagnoses such as obesity and overweight. This designation allows Lilly to complete an application for FDA approval of tirzepatide for this new indication on a rolling basis, as it conducts additional research, rather than complete the application all at once. If results of Lilly’s trial are favorable, the Fast Track designation could mean a quicker FDA approval of tirzepatide for obesity and overweight, and possibly a faster entry to market, the company notes in its release. Lilly also said that its research, part of a trial called SURMOUNT-2, may be completed by late April 2023. The news follows early speculation from experts that Mounjaro could be rebranded as an obesity drug, after study results revealed the weight loss potential of the drug in people with type 2 diabetes and obesity, and obesity independent of a type 2 diabetes diagnosis. “It was very exciting to hear that this became approved [for type 2 diabetes],” says Robert Gabbay, MD, PhD, the chief science and medical officer for the ADA, in Arlington, Virginia, speaking about tirzepatide’s approval as a type 2 diabetes medication. During the 2021 ADA Scientific Sessions, Dr. Gabbay says, “studies were presented and simultaneously published in the New England Journal of Medicine that led to its approval [for type 2 diabetes]. Now to have tirzepatide available, both clinicians and patients are, to some degree, chomping at the bit to have these kinds of benefits.” And yet, because Mounjaro remains relatively new, questions linger. Gabbay notes that it’s still unclear whether tirzepatide has all the benefits of other GLP-1 drugs in terms of reducing cardiovascular and kidney disease. Early data suggests a potential benefit for the latter. In what was called a “pre-specified exploratory analysis,” Hiddo L. Heerspink, PhD, PharmD, of the University Medical Center Groningen in the Netherlands, reported at ADA Scientific Sessions that people taking tirzepatide in the SURPASS-4 clinical trial experienced fewer renal, or kidney, complications than those taking insulin. They had significantly lower rates of new onset macroalbuminuria, a sign of kidney disease in which there’s excess albumin in your urine. Gabbay notes that studies on the potential cardiovascular benefits are ongoing. Another common question around tirzepatide, and its potential obesity drug counterpart, is pricing. The current list price of Mounjaro is $974 for a four-week prescription of all doses, says Pfeiffer. “Each person’s individual insurer and plan will determine the out-of-pocket costs for Mounjaro,” says Pfeiffer, adding that some people may qualify for savings cards to reduce out-of-pocket costs. Disparities in affordability of new diabetes and obesity medications, as well as bariatric surgery, for underinsured or people without insurance was a topic among experts at ADA Scientific Sessions. What is clear now is that the most common side effects of tirzepatide are nausea and diarrhea, and people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 should not take tirzepatide. Gabbay talked more about the medication, explaining how it works, key findings from clinical trials — and what people with type 2 diabetes specifically should ask their doctor if they’re curious about tirzepatide. Everyday Health: How does tirzepatide work to lower A1C and weight in the body? Robert Gabbay: It is mimicking the effect of two different hormones in the body. One is GLP-1, and we have, for a few years now, had medications that do that specifically. The new part about this medicine is that it also has the effect of a second hormone called GIP (gastric inhibitory polypeptide). So, it has the effect of two hormones. It helps affect A1C and weight in a number of ways. When blood sugars are high, it causes the body to release extra insulin, but not too much, so it won’t cause too low a blood sugar level. It slows down emptying of the stomach, so it allows one to feel more full, eat less, and lose weight. And it also has effects on hunger and satiety in the brain (the signals that tell you when to stop eating), leading to weight loss. So, it’s a combination of all these things that improve blood glucose and reduce weight. EH: Who is eligible to take tirzepatide, and at what point in their diabetes journey? For example, after they’re diagnosed or after taking metformin? RG: It’s a good question. It just became available, so we are literally sorting some of that out, and there will be a lot of discussion at our ADA Scientific Sessions this week centered on exactly that issue. It could be used potentially at various points in the journey of people who need both lowering of A1C and improvement in weight. And I think the dramatic thing about this medication is that it has the potential to really have a major effect on weight; it’s more potent than other options we typically have available. It has the opportunity to be quite special. EH: How might tirzepatide change how clinicians approach early treatment of type 2 diabetes with the medication’s potential for dramatic weight loss and the corresponding health benefits, in the immediate future or down the line? RG: Given that most people with type 2 diabetes also have obesity, I think tirzepatide will certainly be an important medication for the treatment of many. We await the results of cardiovascular risk reduction studies to better understand tirzepatide’s role vs. the GLP1 class of medications. EH: How long and how rigorously has it been studied? What are some of the key findings that patients should know about? RG: The way drugs get approved by the FDA is they go through a series of studies to determine safety and dosing. Then they do a larger study to determine if it is better than current treatments (and they do a variety of those). Each study has a safety component. So, it has been studied now in a good number of people, and the findings have been that it significantly lowers weight. In the SURMOUNT-1 study, people without diabetes lost 20 percent of their body weight. In the study, at the highest dose of tirzepatide, people lost an average of 52 pounds, which is a lot. EH: What are the findings around diabetes remission? RG: Diabetes remission is having non-diabetes-range blood glucose levels in the absence of any medical therapy or drug treatment for three months. That is the other exciting piece of the data from this treatment. In one of the trials, people in the early course of diabetes used tirzepatide and as many as 50 percent of people treated went into remission, so that really is dramatic. It gives the opportunity to more realistically think of remission as a goal for the treatment of type 2 diabetes. EH: How does tirzepatide compare with diabetes medications that are out there right now? RG: It’s quite different in a few ways. It’s the first medication that has the effect of those two hormones. That’s why it acts differently. There aren’t a lot of head-to-head studies of tirzepatide versus other medications yet. But it appears, from what they’ve presented, that the weight loss is more significant than that of current treatments. Really the only comparable treatment to tirzepatide for weight loss is bariatric surgery. It does seem to be more potent than other medications we have on the market. Over time, there will be more head-to-head trials to prove that more clearly. EH: With any new medication, there are things we can’t know about safety or efficacy in the general population. What do you see as the potential risks? RG: What we do know is the main side effect is nausea. That’s why the dosage is slowly increased and not everyone tolerates the highest dose. That is a limiting factor. Tirzepatide may not be for everybody, in the same way the current GLP-1 drugs are not for everybody. That we already know, and we’ll get a better sense of that as it’s used in a wider population — what percentage of people can tolerate it versus not. EH: How should patients think about the weight loss that has been achieved with tirzepatide in some of the clinical trials? RG: First, an important message is that people shouldn’t be stigmatized about their weight. Weight loss is challenging. Obesity is a disease. We are developing better treatments. This is one potential treatment for obesity associated with diabetes. It has promising results. Maybe we need to rethink what treatment of obesity in the setting of diabetes looks like. If someone needs treatment, then they need treatment. EH: What else should patients know about this medication? RG: As wonderful as we’ve described it, it doesn’t let us off the hook of doing the things that are good for our health in terms of managing the quantity and the quality of the foods we’re eating and getting physical activity. Those are still important. The goal is, do those, and then potentially use medication to augment that and make you more successful. EH: Sometimes there was low participation in clinical trials of tirzepatide by Black adults compared with white adults. And Black adults are more likely to have diabetes than white adults. What do you think this means for the drug’s efficacy in that population? RG: One thing the ADA has really been working on and engaged with the FDA on is to improve participant diversity in clinical trials. This is not just true for the tirzepatide trials. If you look across all diabetes medication and device trials, the participation rates of Black, Indigenous, and People of Color (BIPOC) communities are quite low and don’t represent the fact that these individuals are more adversely affected or at risk for diabetes. We hope to see progress in this area and have been advocating strongly for it. EH: Can tirzepatide be combined with other medications? RG: Yes, it appears it can be combined with standard diabetes medications that are not GLP-1 drugs, but we’ll need more of that data to be sure. It will be interesting to see. EH: What questions should patients ask their doctors about tirzepatide? RG: Would I be eligible for this drug? It’s important to hear from their provider about what the downsides or side effects might be. That’s true anytime you start something new. Have a conversation with your healthcare provider to decide if it’s right for you. With obesity being an underlying issue for most people with type 2 diabetes, this new treatment is a potential game changer. Editor’s note: Answers have been edited for clarity and concision. Disclosures: Gabbay disclosed that he is on the advisory board for Lark, Health Reveal, Vida Health, Onduo, and Sweetech.
