Genetic test will predict the efficacy of semaglutide for weight loss

A risk assessment biomarker that identifies the “hungry stomach” phenotype could help determine how likely semaglutide-based drugs like Vegovi are to help a person lose weight, according to research presented at the Digestive Disease Week 2024 conference.

Researchers have developed machine learning to calculate the genetic risk of "hunger stomach," a condition that occurs when a person eats but feels hungry again an hour or two later because the stomach empties quickly.

The study involved 84 people with obesity or other weight management issues. Saliva or blood samples were collected for genetic analysis and information about the participants' eating habits was collected.

Participants took a drug based on semaglutide for one year. The scientists recorded total body weight loss at months 3, 6, 9 and 12. They then determined the likelihood of a positive response to semaglutide depending on the type of weight management problem.

Semaglutide and Weight Loss Study Details

Researchers at the Mayo Clinic in Minnesota have developed a test called MyPhenome that categorizes obesity phenotypes, which can help improve weight loss. There are four types:

• Hungry Brain - Eating too many calories without feeling full.
• Hungry stomach - eating a full meal, but quickly feeling hungry.
• Emotional hunger is eating in response to an emotional trigger.
• Slow metabolism means you burn calories too slowly.

The researchers used observations of adults undergoing weight loss treatment, focusing on those prescribed semaglutide.

The researchers reported that people with a positive fasting phenotype lost 14% of their body weight after 9 months, compared with 10% for those with a negative phenotype.

After 12 months, those with a positive fasting phenotype had lost 19% of their total body weight. Those with a negative phenotype remained at around 10% body weight loss.

How semaglutide research could be useful

All people react to medications differently.

But the researchers say the genetic test explains the differences and allows doctors to target the underlying cause of obesity. They believe the phenotype test could be used in medical settings to determine who will respond well to semaglutide.

The presentation suggests the test is 75% accurate in predicting who will respond to semaglutide, without the need for "trial and error" to determine whether the drug works.

"Severe obesity is deadly," said Dr. Mitchell Roslin, chief of bariatric surgery at Northwell Lenox Hill Hospital in New York City, who was not involved in the study. "It creates a phase transition. So people's bodies are 10 to 20 years older than their chronological age. Heart disease is the leading cause of death."

Semaglutide is a relatively new drug for treating obesity. Insurance companies do not always cover its cost. Out-of-pocket payments can reach up to $1,000 per month.

Researchers say knowing whether a drug will work could help doctors and patients better decide whether to try it.

"Like all medications, semaglutide has side effects. People may experience gastrointestinal symptoms such as nausea, vomiting, diarrhea or constipation," said Dr. Mir Ali, a bariatric surgeon and medical director of the MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in California.

"Usually the side effects go away as the body adapts to the drug. However, it is important to start at the lowest dose and increase as needed," said Ali, who was not involved in the study.

Limitations of Genetic Testing for Weight Loss Drugs

Not all physicians plan to use risk assessment in their practice.

"I probably wouldn't use a risk calculator to determine whether one of my patients should or shouldn't use semaglutide," Ali said. "There are a lot of calculators out there that may or may not be helpful. Using calculators is cumbersome, and I probably wouldn't ask patients to spend extra money on genetic testing."

Ali said he considers various factors before prescribing a weight loss drug. These factors include:

• How much excess weight a person has.
• What is his body mass index (BMI).
• What weight loss strategies have been used in the past and how effective have they been?
• Do they meet the criteria for bariatric surgery?

"Weight-loss surgery is still the most effective for weight loss and maintenance," Ali said. "If they don't meet the criteria for surgery, I'll look at GLP-1 analogs like semaglutide."

"It's important to remember that no matter what treatment method is used, the goal is to change habits, develop healthy eating habits and make lifelong changes," Ali stressed.

Roslin agrees. "We're trying to teach people how to use weight loss tools in the best possible way," he said.