GLP-1s, Surgery and Nutrition: Experts on the New Era of Weight Management

GLP-1 medications have reshaped how doctors treat obesity in just a few years. But according to experts from Montefiore Einstein, they work best as one part of a broader plan that can include surgery, nutrition support and lifestyle changes.

At a recent virtual media briefing, Sriram Machineni, M.D., director of the Fleischer Institute Medical Weight Center; Jenny Choi, M.D., director of bariatric surgery; and Monica Kelly, M.S., R.D., a registered dietitian, discussed how these treatments fit together.

Obesity Is About Health Risk, Not Just the Scale

Machineni explained that obesity is defined as an abnormal or excessive buildup of fat that poses a risk to health. Body mass index (BMI) is widely used to classify it, but it doesn’t directly measure body fat.

Treating obesity matters because it causes or worsens roughly 200 medical conditions, including Type 2 diabetes, obstructive sleep apnea and degenerative arthritis. He said treatment options range from diet and exercise changes to expert support, medications and surgery. Doctors often combine these based on the severity of a patient’s condition.

“It’s actually not a ladder,” he said.

From Lizard Venom to Today’s Weekly Injections

The road to GLP-1s began decades ago. In 1992, researchers found a molecule in Gila monster venom that acts on the same receptors as the GLP-1 hormone. That discovery led to exenatide, the first GLP-1 receptor agonist approved for Type 2 diabetes in 2005. Liraglutide became the first GLP-1 approved for obesity in 2014. Since then, newer once-weekly options, semaglutide and tirzepatide, have become the most effective treatments available.

These drugs are also being approved for conditions beyond weight loss. In December 2024, the FDA approved tirzepatide (Zepbound) as the first medication for moderate to severe obstructive sleep apnea in adults with obesity. In the trial that led to approval, 42% of participants on tirzepatide alone achieved remission or mild, nonsymptomatic sleep apnea after one year. Among those also using PAP therapy, it was 50%.

How Real-World Results Compare With Clinical Trials

Clinical trials show tirzepatide produces more weight loss than semaglutide. But Machineni said the gap narrows in everyday practice. A real-world analysis called SHAPE, published in Advances in Therapy, found average one-year weight loss of 16.5% with tirzepatide, compared with 14.1% with semaglutide. That works out to roughly 38 pounds versus 32 pounds. Machineni noted that about 85% of people in both groups lost at least 5% of their body weight, which is considered clinically meaningful.

Other real-world data show wider differences. A 2026 study in PNAS Nexus of more than 20,000 matched patients found average weight loss of 14.7% with tirzepatide and 10.8% with semaglutide. Results vary depending on dose, how long people stay on treatment and who is studied.

In his practice, Machineni typically starts patients on a low dose of semaglutide and increases it gradually. He switches to tirzepatide if a patient isn’t tolerating the medication or isn’t losing enough weight.

“We don’t always try to get them to the highest dose because now more and more data [are] coming out which says that there’s no need to push to the highest dose to get the best results,” he said.

More Options on the Way

The field keeps expanding. In April, the FDA approved orforglipron (Foundayo), a once-daily GLP-1 pill that can be taken without food or water restrictions. Retatrutide, an investigational drug that targets three hormone receptors, produced an average 25% weight loss at its highest dose over 80 weeks in a Phase 3 trial. Some participants reached up to 30%, which approaches results seen with bariatric surgery.

“About 15 to 20 percent of total weight loss is a sweet spot for quality of life and comorbidity improvement, and we are already there with the present medications,” Machineni said.

Bariatric Surgery’s Changing Role

Choi acknowledged the appeal of avoiding surgery.

“The reality is, who really wants to have surgery if they can avoid it, right? I mean, I’m a surgeon, and I would not want to have surgery, so I completely understand the sentiment,” she said.

National data reflect that shift. According to the American Society for Metabolic and Bariatric Surgery, U.S. bariatric procedures fell from about 230,000 in 2022 to about 177,000 in 2024. The organization notes that fewer than 1% of eligible people have the surgery in any given year.

Today, most new patients Choi sees have already tried medication. Some stopped because of side effects such as nausea, vomiting, reflux or constipation. Others stopped because of cost, regained weight after tapering off or didn’t lose enough weight. Weight regain after stopping is well documented. In an extension of the STEP 1 trial, people regained about two-thirds of the weight they had lost within a year of stopping semaglutide.

Medications now play a supporting role in surgical care too. Choi said some patients who regain weight after surgery may benefit from medication rather than another operation. GLP-1s can also help high-risk patients lose weight before surgery, or help patients with very high BMIs get more out of a first procedure.

She said bariatric surgery remains more effective than current medications and will continue to have a place, especially for patients with very high BMIs and those who have tried other options.

Smaller Portions of Better Food

Choi and Machineni both noted that GLP-1s affect appetite through the brain, much like bariatric surgery.

“These medications are not simply acting on the stomach; they work on the brain,” Machineni said.

But less appetite doesn’t automatically mean better choices.

“Yes, it takes away your appetite, but you can’t eat less of the same junk you’re eating. You have to eat smaller portions of the better things, right?” Choi said.

Nutrition Priorities for People on GLP-1s

Kelly’s approach follows a 2025 joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association and The Obesity Society. It focuses on managing digestive side effects, preventing nutrient deficiencies and preserving muscle mass.

“We know that with these medications, their appetite decreases, so that means they’re eating less, which is the purpose of the medication. But are they eating enough to not become nutritionally deficient in something?” she said.

The advisory notes that GLP-1s can cut daily calorie intake by 16% to 39%. That can make it harder to get enough nutrients such as iron, calcium, vitamin D and vitamin B12.

Kelly recommends the following:

• Prioritizing protein to help preserve muscle. The advisory suggests 1.2 to 1.6 grams of protein per kilogram of body weight per day during active weight loss, or roughly 80 to 120 grams per day.
• Eating high-fiber foods to support digestion. The advisory recommends increasing fiber gradually, with enough fluids.
• Cutting back on ultraprocessed, high-fat and fried foods, and processed meats. These can slow weight loss and worsen side effects.

Managing side effects is essential to staying on treatment. Kelly cited one large study in which about 40% of patients reported nausea and about 20% reported vomiting. That’s consistent with the advisory, which found nausea in 25% to 44% and vomiting in 8% to 24% of clinical trial participants.

She also urged patients to add strength or resistance training, not just walking or aerobic exercise. In the STEP 1 trial, about 38% of the weight participants lost was lean mass, and the joint advisory notes that protein alone likely isn’t enough to preserve muscle without regular strength training.