How promising are new drugs to treat obesity and who should — and shouldn't — use them?

B.C. bans some online Ozempic sales New regulations in B.C. prevent online sales of the diabetes drug Ozempic to people who reside outside of the province or Canada.

The pharmaceutical company Eli Lilly announced last week that a medication developed to treat diabetes, tirzepatide, also had a substantial effect on reducing weight.

Among the more than 900 adults with obesity and diabetes in a study, tirzepatide not only controlled their blood sugar but also helped those on the higher dose lose an average of 34 pounds, which was nearly 16 per cent of their starting weight, according to a company news release. The participants took the drug for a year and five months.

Eli Lilly plans to file for approval by the U.S. Food and Drug Administration to market tirzepatide for treating obesity.

Another pharmaceutical company, Novo Nordisk, manufactures the medication semaglutide, which the FDA has already approved to treat diabetes under the brand name Ozempic and to treat obesity under the brand name Wegovy. Celebrities have claimed to use it as a weight-loss tool, and its widespread use has triggered medication shortages.

How exactly do semaglutide and tirzepatide work? How promising are they to treat obesity? What are the side effects? Who is eligible? What if someone wants to lose a few pounds for a wedding or event — should they take them?

To help us with these questions, CNN Medical Analyst Dr. Leana Wen. Wen, who is an emergency physician and professor of health policy and management at the George Washington University Milken Institute School of Public Health, explains. She previously was Baltimore's health commissioner.

HOW DO THESE MEDICATIONS WORK?

Dr. Leana Wen: Both of these injection medications were initially developed to treat type 2 diabetes. In the process of doing clinical trials, research also found that they have a substantial effect on weight loss.

Semaglutide mimics a digestive hormone called glucagon-like protein-1, or GLP-1, that's released by intestines when we eat. This hormone promotes insulin production, which encourages cells to take up glucose and therefore to reduce blood glucose levels. GLP-1 also slows gastric emptying and prolongs the sensation of feeling full. In addition, it suppresses appetite, resulting in people wanting to eat less and inducing weight loss.

Tirzepatide mimics GLP-1 as well as another hormone released by the gut to stimulate insulin production called glucose-dependent insulinotropic polypeptide (GIP). While GIP isn't as well studied as GLP-1, it appears to have a similar effect to it. Tirzepatide has this dual effect on GLP-1 and GIP, while semaglutide targets just GLP-1. It's important to note that we do not have study results comparing these two medications side by side.

HOW PROMISING ARE THESE DRUGS TO TREAT OBESITY?

Wen: Of the two medications, semaglutide is the one that's better studied. A 2022 study, published in JAMA Network Open, found that study participants' mean weight loss after taking it for three months was 6.7 kilograms (14.8 pounds), or 5.9 per cent body weight reduction. After six months, it was 12.3 kilograms (27.1 pounds), or 10.9 per cent.

Another study, published in The New England Journal of Medicine, found a mean loss of body weight of 14.9 per cent from baseline to more than a year later in the semaglutide group, compared with 2.4 per cent in the placebo group.

According to the news release from Eli Lilly, it appears that the company achieved a very high rate of weight loss as well. For those taking the higher dose of tirzepatide, patients lost an average of 15.6 kilograms (34.4 pounds), which was equivalent to a 15.7 per cent body weight reduction, at over a year of treatment. These results are not yet published in a peer-reviewed publication, but if they hold up, these would be really excellent results as well.

I think the key to emphasize here is that obesity is a chronic medical condition that increases the risk of developing many other diseases, including heart disease, diabetes, high cholesterol and many forms of cancers. Patients with obesity also experience higher rates of sleep apnea, arthritis, back pain and depression, and they are at higher risk for early mortality. It is really important to treat obesity as the disease that it is — and having effective medications to do so is crucial.

WHAT SIDE EFFECTS SHOULD PEOPLE BE AWARE OF?

Wen: Virtually all medications and therapies have side effects. These are no different.

The most common side effects are gastrointestinal discomforts, such as nausea, diarrhea, vomiting and constipation. The medications have been associated in rare cases with pancreatitis and gallbladder problems, and some patients may experience low blood sugars while taking them. Some animal studies have linked them to thyroid tumours — and although this has not been seen in humans, patients are advised against using either of these medications if they or their family members have had a type of thyroid cancer known as medullary thyroid carcinoma.

In addition, these are injection medications. As such, there could also be pain, swelling and redness at the injection site. And because these medications are relatively new, long-term effects are not known, and it is also not known as to how long people should continue taking them.

Anecdotally, many patients have had their weight rebound back soon after stopping.

WHO IS ELIGIBLE TO TAKE THEM?

Wen: Semaglutide is marketed under the brand name of Ozempic for treatment of diabetes and Wegovy for treatment of obesity. For Ozempic, it is approved only to treat type 2 diabetes. For Wegovy, patients are eligible if they have a body mass index, or BMI, at or over 27. They are to use it together with lifestyle modifications, including increased physical activity and improved diet.

Tirzepatide, also known as brand name Mounjaro, is only approved by the FDA to treat type 2 diabetes. However, like other prescription medications, it can be prescribed for what's called off-label use by physicians. Some physicians prescribe Mounjaro and Ozempic for treatment of obesity, even though (they are) not approved by the FDA for this purpose.

WHO SHOULDN'T TAKE THESE DRUGS?

Wen: Well, you just described the type of person who should not take these medications. Type 2 diabetes and obesity are serious medical conditions. These medications should be reserved for individuals with these conditions.

These are not medications to be taken by nondiabetic people who do not have obesity. In addition, individuals who are considered overweight or to have obesity based on BMI may not need these medications. In general, just like for other chronic conditions of hypertension and diabetes, people should try lifestyle modifications first. Only if these modifications do not work should medications be considered in consultation with your doctor, and even then, the lifestyle changes should continue.

I want to emphasize that these are not medications to be used for vanity purposes. Someone who is trying to lose a few pounds for a wedding or event should not take them for several reasons. First, it's very likely that once that person stops taking the medication, the weight will come right back. Second, there are better ways to lose weight, and, more importantly, to maintain good health. Third, this is not what the medication is intended for. Given the medication shortages that have occurred, a person taking it for this kind of short-term use could be taking it away from patients who really need it for their medical conditions.