UB pharmacy professor discusses pros and cons of popular weight-loss drugs

BUFFALO, N.Y. — Popular prescription drugs such as Ozempic, Wegovy and Zepbound have transformed the way overweight and obese individuals shed pounds. So-called weight-loss drugs have achieved such a heightened status over the past year that Morgan Stanley research analysts estimate that as much as 9% of the U.S. population will be taking these drugs by 2035.

In the future, such drugs also could be used to address alcoholism and other addictions. Researchers in Sweden examined more than a quarter million people with alcohol-use disorder and found those who had taken Ozempic and Wegovy cut their risk for hospitalization. It is one of a handful of recent studies showing the connection between weight-loss drugs and reduced drinking.

However, the expense and troubling side effects of the drugs may limit their appeal for some.

Nicole Albanese, PharmD, clinical associate professor in the Department of Pharmacy Practice in the University at Buffalo School of Pharmacy and Pharmaceutical Practices, discusses the science behind weight-loss drugs, their potential to treat other addictions as well as possible dangers.

Albanese, whose specialties are diabetes, obesity and nutrition, also serves as the program director for the UB-Buffalo Medical Group PGY2 Ambulatory Care Residency Program.

Are these drugs more effective than weight loss drugs of the past because patients feel satisfied after eating smaller amounts of food?

Yes. The semaglutide in Ozempic and Wegovy mimics the glucagon-like peptide-1 (GLP-1) hormone that is released in the gastrointestinal tract in response to eating. This prompts the production of insulin and sends a signal to your brain, saying, “We’ve had enough food and we’re full.”

Tirzepatide, sold under the brand names Mounjaro (for Type 2 diabetes) and Zepbound (for weight loss), is a once-weekly injectable drug that works by mimicking two hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) — the two gut hormones that help regulate blood sugar, digestion and appetite.

Obviously, people who are obese make way less of the hormones, and people who are super skinny are probably making too much of them. Also, taking the drug over time usually changes the foods patients want to eat. They may have loved potato chips before, but now that food turns them off.

Will the prevalence of these drugs significantly reduce diabetes and other obesity-related disease?

Yes and no. From a strictly scientific point of view, these drugs could revolutionize how overweight and obese patients are treated. But the people who typically need these drugs aren’t able to access them. Both the real version of the drugs and the compounded (reformulated or customized) versions are still very expensive, and only people who can afford to pay out of pocket are getting access to them. These drug classes represent just the first iteration of drug therapy to treat overweight and obesity. The good news is many other therapies are in discovery and trials that will continue to revolutionize this therapeutic area.

Do people need to stay on the drug to prevent regaining the weight?

That is what all the early data is telling us. They’ve done a number of studies and for people who have been on a weight-loss drug for a year or two and then go off, they usually regain around 50% of the weight they lost.

It’s also true that a small subset of people who exercise regularly and completely change the way that they eat, including eating less processed and lower calorie food — can maintain the weight loss.

Because I’ve been dealing with these behaviors for so long I think we probably need to see five years’ worth of data. Within five years, someone who had bad habits before they started taking the drug has retrained their brain into new habits. I have a friend who lost about 50 pounds with a GPI-1 two years ago, but she still over-orders food in restaurants, although she can’t finish it. Or she’ll say, “I’m starving,” and reach for a bag of potato chips or M&Ms instead of healthy food. For two years, she’s had this feeling of fullness and nausea, but she still wants to overeat and not make good food choices. So, I really think you need more time to gauge success.

Did you anticipate these drugs becoming so popular?

I didn’t anticipate where we are now in that celebrities would have gotten on board, that the success of the drugs would be all over social media, and there would be all these drug compounds.

But we did learn early on that the diabetes drugs could result in amazing weight loss. I knew that these weight-loss studies were occurring and that the drugs eventually would get approved for weight loss in patients without diabetes. I also knew that it was going to be restricted. A lot of people just can’t get the drugs when insurance doesn’t cover them.

So, health insurance typically does not cover weight-loss drugs?

It depends. Government plans don’t cover them. Medicare and Medicaid don’t even recognize obesity as a disease state, so they don’t cover any weight-loss medications. However, they are considering it now that some have the indication of cardiovascular risk reduction. If the drugs are going to help prevent heart attacks and strokes, they probably will have to cover them.

In response to the craze that’s happening with these drugs, insurance companies are locking it down and saying, “Actually we’re not going to cover GLP-1 for prediabetes.” And they certainly don’t cover drugs such as Ozempic and Mounjaro if you just have a strong family history or are considered prediabetic. You have to wait until you actually have a diabetes diagnosis.

Because of the way our health care system works, including mandatory insurance for everybody, many people have high deductible plans. If you have to spend $10,000 or even $5,000 of your own money before insurance kicks in, that’s just not affordable for most people. And on top of that, insurance companies are putting stricter guidelines in place for people to continue taking the drugs.

What do you think about using these drugs to treat alcohol addiction and other addictions?

The science behind it makes total sense based on what we know about how the drugs work. They curb appetites by working directly in the “reward center” of the brain. That is where addictions happen as well. So, you can see how a drug that reduces appetites could work for other kinds of cravings and addictions. I’m really interested to see what ongoing studies will show about using weight-loss drugs for alcohol and drug addiction.

What are common side effects of the weight-loss drugs?

The most common is nausea, which I believe is controllable. You need to eat less and maybe more often. The key is to stop eating the first second you feel full because it takes a while for food to get to your stomach and then signal to your brain that you’re full.

I’m more concerned about serious side effects such as gallbladder disease and pancreatitis. We’re seeing this because more people are taking these drugs at super high doses. The side effects are pretty linear at the low dose, but as you increase the dosage, the side effects go up, and there could be irreversible damage.

Another risk is how the drugs interact with oral contraceptives. Weight-loss drugs slow down your gut and oral contraceptives aren’t going to work the way women are used to them working. They may need to change to the patch or an IUD, and that sometimes gets lost in translation with providers and even pharmacists who are focused on getting the patient the weight-loss drug.

Also, anesthesiologists are realizing that because of that slow-down function in the gut, the drugs they’re giving patients are not working as well as they did before. So, if you’re on these drugs and you’re scheduled for surgery, you have to stop them at least a week before surgery. But that message isn’t getting out to everybody. And people may be reluctant to stop since they’re only taking the injection once a week. They may decide just to stay on it despite the surgery, and that can be dangerous.

Are there other dangers associated with these drugs?

Yes, a new warning about increased suicidal ideation recently came out in Europe. The U.S. Food and Drugs Administration (FDA) has said that there doesn’t appear to be any substantiated data on suicidal ideation, but studies are ongoing.

However, people who take these drugs typically have more depression even after losing the weight. You would think it would be the opposite, right? You lose weight and you start to feel better about yourself, but that is not always the case. I think it’s more complicated than that.

You don’t feel good about yourself and you blame it on being overweight or obese. When that is taken away, you still don’t feel good about yourself. It wasn’t the weight that was causing the depression. It was tied to other factors that you haven’t figured out yet.