May 11, 2023 – They’re both popular ways to lose weight. Anti-obesity medications like semaglutide (Wegovy) and liraglutide (Saxenda) are in such high demand that drugmakers sometimes report shortages. And gastric sleeve surgery – a procedure that shrinks stomach size by up to 80% – remains the most common intervention for weight loss.
Research shows both strategies can lower total body weight, but little is known about what happens when you combine them.
Is it better to take weight loss medication first, and then reduce stomach size – or the other way around? If you’re going to do both, how much time should you wait?
Investigators are starting to answer these and other questions that could help the 42% of Americans with obesity.
Adding medication appears to help people lose more total body weight than the gastric sleeve alone, according to a study at Digestive Disease Week (DDW) 2023. DDW is an international meeting of gastrointestinal doctors, nurses, and other providers that had 13,000 virtual and in-person attendees this year.
In the study of 224 people with obesity, 69 had the combination of medication and the gastric sleeve procedure. Having both within 6 months of each other was considered “combination therapy.” This approach was linked to the most weight loss: an average of 24% of total body weight by 1 year.
Gastric sleeve surgery was done endoscopically in the study – a minimally invasive procedure known as gastroplasty. Instead of cuts in the stomach, specialists known as bariatric endoscopists insert a flexible tube down the throat and use a special instrument on the end to make the stomach smaller.
Different Anti-Obesity Drugs Studied
The combination group took different anti-obesity medications. About one-third took a glucagon-like peptide-1 agonist, or a GLP-1 for short, such as semaglutide and liraglutide. Other medications included phentermine/topiramate extended-release capsules (Qsymia) or a combination of bupropion and naltrexone extended-release for weight loss (Contrave).
When combined with gastroplasty, these other drugs led to 18% total body weight loss at 1 year.
Another 77 people in the study had sleeve gastroplasty alone. They lost an average 17% of their total body weight.
A third group of 78 people had “sequential therapy,” which means they started medication more than 6 months before or after gastroplasty. This group had the least amount of weight loss – 14% of total body weight at 1 year if gastroplasty came first and 12% if medication came first.
Waiting for weight loss to start to plateau after gastroplasty might be an ideal time to add weight loss medication, said Pichamol Jirapinyo, MD, a bariatric endoscopist at Brigham and Women’s Hospital in Boston. “Usually when I see them at 3 months, I plot how fast their weight loss has been. If it’s been going down [steadily], we do not offer an anti-obesity medication until I see them again at 6 months.”
Not every patient offered weight loss medication is interested, said Jirapinyo, the lead researcher on the study.
The serious side effect rate for gastroplasty was similar among groups: 2.6% for the group that only got the procedure, 1.4% with combination therapy, and 1.3% with sequential therapy. Side effects linked to anti-obesity medication occurred in 1.3% of the sequential therapy group – and was not reported in either of the other two groups.
Combo Makes Sense
“I certainly think combination therapy should be more effective than just gastroplasty alone and is probably better," said Gregory L. Austin, MD, a gastroenterologist at the UCHealth Digestive Health Center in Denver.
But the study did not address whether people should still have gastroplasty after being on medication for 6 months or longer. He said they probably should if they’re not seeing enough weight loss that comes with improved health outcomes by that time.
“Whether you start immediately or wait 3 months afterwards is a question that still needs to be answered,” Austin said.
‘Wave of the Future’
The study is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy at Brigham and Women’s Hospital.
Medication begun within 6 months of the endoscopic procedure “led to superior outcomes compared to just endoscopy alone,” she said.
“I think that's really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough,” Lee said. “Of course, we have [bariatric] surgery, but we also realize that with surgery, sometimes the weight starts to creep back up over time.”
“From my point of view, as long as the medicine is safe and not harming them, then let's do both of them together,” she said.