Optimal Time Period for Weight Loss Drugs: Debate Continues

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Optimal Time Period for Weight Loss Drugs: Debate Continues

Ashley Lyles

April 18, 2023

After bariatric surgery in 2014, Kristal Hartman still struggled to manage her weight long term. It took her over a year to lose 100 pounds, a loss she initially maintained, but then gradually her body mass index (BMI) started creeping up again.

“The body kind of has a set point, and you have to constantly trick it because it is going to start to gain weight again,” Hartman, who is on the national board of directors for the Obesity Action Coalition, told Medscape Medical News.

So, 2.5 years after her surgery, Hartman began weekly subcutaneous injections of the glucagon-like peptide-1 (GLP-1) agonist semaglutide, a medication that is now almost infamous because of its popularity  among celebrities and social media influencers.

Branded as Ozempic for type 2 diabetes and Wegovy for obesity, both contain semaglutide but in slightly different doses. The popularity of the medication has led to shortages for those living with type 2 diabetes and/or obesity. And other medications are waiting in the wings that work on GLP-1 and other hormones that regulate appetite, such as the twincretin tirzepatide (Mounjaro), another weekly injection, approved by the US Food and Drug Administration (FDA) last May for type 2 diabetes and awaiting approval for obesity.

Hartman said taking semaglutide helped her not only lose weight but also “curb [her] obsessive thoughts over food.” To maintain a BMI within the healthy range, as well as taking the GLP-1 agonist, Hartman relies on other strategies, including exercise, and mental health support.

“Physicians really need to be open to these FDA-approved medications as one of many tools in the toolbox for patients with obesity. It’s just like any other chronic disease state, when they are thinking of using these, they need to think about long-term use…in patients who have obesity, not just [among those people] who just want to lose 5 to 10 pounds. That’s not what these drugs are designed for. They are for people who are actually living with the chronic disease of obesity every day of their lives,” she emphasized.

On average, patients lose 25% to 40% of their total body weight following bariatric surgery, said Teresa LaMasters, MD, president of the American Society for Metabolic & Bariatric Surgery. However, there typically is a “small” weight regain after surgery, she added.

“For most patients, it is a small 5 to 10 pounds, but for some others, it can be significant,” said LaMasters, a bariatric surgeon at UnityPoint Clinic, Des Moines, Iowa.

“We do still see some patients — anywhere from 10% to 30% — who will have some [significant] weight regain, and so then we will look at that,” she noted. In those cases, the disease of obesity “is definitely still present,” she added

Medications Can Counter Weight Regain After Surgery

For patients who don’t reach their weight loss goals after bariatric surgery, LaMasters said it’s appropriate to consider adding an anti-obesity medication. The newer GLP-1 agonists can lead to a loss of around 15% of body weight in some patients.

“The GLP-1 agonists have been very helpful for treating patients who’ve had bariatric surgery and had some weight regain, or even just to optimize their initial response to surgery if they are starting at a very, very severe point of disease,” she explained.

She noted, however, that some patients shouldn’t be prescribed GLP-1 agonists, including those with a history of thyroid cancer or pancreatitis.

Caroline M. Apovian, MD, codirector of the center for weight management and wellness and professor of medicine at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News that the physiology behind bariatric surgery and that of the newer obesity medications is somewhat aligned.

“In order to reduce…body weight permanently you need adjustments. We learned that you need the adjustments of the hormones [that affect appetite, such as GLP-1], and that’s why bariatric surgery works because…[it] provides the most durable and the most effective treatment for obesity…because [with surgery] you are adjusting the secretion and timing of many of the hormones that regulate body weight,” she explained.

So, when people are taking GLP-1 agonists for obesity, with or without surgery, these medications “are meant and were approved by the FDA to be taken indefinitely. They are not [for the] short term,” Apovian noted.

Benjamin O’Donnell, MD, an associate professor at The Ohio State University Wexner Medical Center, Columbus, agreed that the newer anti-obesity medications can be very effective; however, he expressed uncertainty about prescribing these medications for years and years.

“If somebody has obesity, they need medicine to help them manage appetite and maintain a lower, healthier weight. It would make sense that they would just stay on the medicine,” he noted.

But he qualified: “I have a hard time committing to saying that someone should take this medication for the rest of their life. Part of my hesitation is that the medications are expensive, so we’ve had a hard time with people staying on them, mostly because of insurance formulary changes.”

Why Stop the Medications? Side Effects and Lack of Insurance Coverage

Many people have to discontinue these newer medications for that exact reason.

When Hartman’s insurance coverage lapsed, she had to go without semaglutide for a while.

“At that time, I absolutely gained weight back up into an abnormal BMI range,” Hartman said. When she was able to resume the medication, she lost weight again and her BMI returned to normal range.

These medications currently cost around $1400 per month in the US, unless patients can access initiatives such as company coupons. Some insurers, including state-subsidized Medicare and Medicaid, don’t cover the new medications.

O’Donnell said, “More accessibility for more people would help in the big picture.”

Other patients stop taking GLP-1 agonists because they experience side effects, such as nausea.

“Gastrointestinal complaints…are the number one reason for people to come off the medication,” said Disha Narang, MD, an endocrinologist and obesity medicine specialist at Northwestern Medicine Lake Forest Hospital, Illinois.

“It is an elective therapy, so it is not mandatory that someone take it. So if they are not feeling well or they are sick, then that’s a major reason for coming off of it,” she said.

Dan Bessesen, MD, professor of medicine at the University of Colorado Anschutz Medical Campus, Denver, and chief of endocrinology, agrees.

Patients are unlikely to stay on these medications if they feel nauseous or experience vomiting, he said. Although he noted there are options to try to counter this, such as starting patients on a very low dose of the drug and up-titrating slowly. This method requires good coordination between the patient and physician, he stressed.

Goutham Rao, MD, a professor of medicine at Case Western Reserve University School of Medicine Cleveland, Ohio, and head of the weight loss initiative Fitter Me at University Hospitals, said that prior to prescribing GLP-1 agonists for weight loss, he sets four basic, non-negotiable goals for patients: “to have breakfast within 30 minutes of getting up, to drink just water, no food or drink after 7:00 PM except for water, and 30 minutes of continuous exercise per day, which is typically, for older clientele, walking.”

This, he said, can help establish good habits because if “patients are not engaged psychologically in weight loss…they expect the medication to do [all] the work.”

Most Regain Weight After Stopping Obesity Medications

As Hartman’s story illustrates, discontinuing the medications often leads to weight regain.

“Without the medicine, there are a variety of things that will happen. Appetite will tend to increase, and so [patients] will gradually tend to eat more over time,” Bessesen noted.

“So it may take a long time for the weight regain to happen, but in every study where an obesity medicine has been used, and then it is stopped, the weight goes back to where it was on lifestyle alone,” he added.

In the STEP 1 trial, almost 2000 patients who were either overweight or living with obesity were randomized 2:1 to semaglutide, titrated up to 2.4 mg each week by week 16, or placebo in addition to lifestyle modification. After 68 weeks, those in the semaglutide group had a mean weight loss of 14.9% compared with 2.4% in the placebo group.

Patients were also followed in a 1-year extension of the trial, published last year in Diabetes, Obesity, and Metabolism.

Within 1 year of stopping treatment, participants regained two thirds of the weight they had initially lost.

Hence, Bessesen stressed that a total rethink of how obesity is approached is needed among most physicians.

“I think in the future treating obesity with medications should be like treating hypertension and diabetes, something most primary care doctors are comfortable doing, but that’s going to take a little work and practice on the part of clinicians to really have a comfortable conversation about risks, and benefits, with patients,” he said.

“I would encourage primary care doctors to learn more about the treatment of obesity, and learn more about bias and stigma, and think about how they can deliver care that is compassionate and competent,” he concluded.

Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University’s Science, Health, and Environmental Reporting Program. Previously, she studied professional writing at Michigan State University. Her work has taken her to Honduras, Cambodia, France, and Ghana, and has appeared in outlets like The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, TCTMD, Insider Health, and Tonic (Health by Vice), among other publications.

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