Experts reveal why 15 percent of people don't lose weight on Ozempic – could you be a 'non-responder'?

Ozempic and similar fat-burning shots have been a godsend for millions of Americans living with obesity.

At least 5.6 million people across the US have been prescribed the injection to help them slim down and, in doing so, slash their risk of a host of diseases by 20 percent.

The medicine, which works by supressing hunger signals, can help patients lose up to 15 percent in their body weight in just over a year, according to major trials.

But while may have great success dropping pounds, some one in six patients don’t in fact any lose weight at all – or lose so little it’s barely noticeable. 

They are the curious group that some doctors have taken to calling, ‘Ozempic non-responders’.

Experts are baffled by this patient group; some of who gain some weight but quickly plateau, while others barely shift anything.

Doctors working in the field believe a combination of genetics, thyroid problems and bad food choices can all work to render the blockbuster medication effectively useless.

Clinical trials of Ozempic, Zepbound, Mounjaro and similar drugs show that about 15 percent of patients are ‘non-responders’, meaning they lose less than five percent of their body weight over about 68 weeks. 

For a 250-pound-man taking the drugs, five percent lost, or twelve and a half pounds, is far lower than the study average of 15 percent lost, or 37 pounds. 

Since the conclusion of those trials, some people, including many Reddit users, have said they actually gained weight on the medicines, with one person saying they put on 13 pounds.

TikTok user Shelly eventually dosed up to the highest level of Ozempic for five months – and it still did not work for her.

‘It did quiet the food noise; I didn’t feel like I was thinking about food all the time, but no weight loss. I could still eat like normal, and a lot of acid reflux that I didn’t want anymore.’

She said it was sad for her to have gotten the medication after having gained weight following a leg injury, and still see no weight loss. She did, however, experience a lot of acid reflux. 

She is no longer taking a weight loss drug but has instead immersed herself in exercise, especially heavy weight lifting.  

Another TikTok user named Viola said: ‘I don’t know why it’s not working for me either it’s making me hungry.’

Another TikToker, Katherine, said she was on Wegovy – which contains the same ingredient as Ozempic – for, ‘four or five months, and I didn’t lose anything. I stayed steady. 

‘I’m just maintaining, I’ve been up and down… the same four or five pounds, basically do not go below a certain number, and I just keep bouncing back and forth.’ 

She added that she has gotten frustrated about the plateau, especially given that she has struggled with her weight her whole life.  

And a Reddit user on the drug said: ‘I started Mounjaro last September and lost 30 pounds in 5 months. In February, I had to switch to Wegovy. They started me at the second lowest dose and I worked up to 2.4. I have gained 5 pounds since February… I also have no appetite suppression.’

Annie, a 40 year-old mother of one from Houston, Texas, told DailyMail.com that she was ‘heartbroken’ when Ozempic did not help her lose weight like she had expected.

Annie, who weighed 198 pounds in May 2022, had struggled with her weight for years and found nothing worked to drop the weight after she had her first child. 

When she broached the topic of taking the medications at an appointment with her doctor, Annie said she was ‘very receptive’.

Dr Gitanjali Srivastava, an obesity specialist at Vanderbilt University [pictured] told DailyMail.com that having an underlying condition like PCOS or certain genetic predispositions could make the drugs work less effectively for those people

The physician was a South Asian woman like Annie who, like most South Asian women, had a genetic predisposion to diabetes – so she understood her patient’s concerns.

Annie was excited. She had seen stories of people losing 20, 30 pounds and felt she was on the cusp of a cure for her obesity, promising to get her healthier to be there for her family. 

While she didn’t experience the severe nausea that many do, she didn’t notice any benefits immediately, either. 

Wegovy, Ozempic and Mounjaro are what are known as GLP-1 receptor agonists. Their active ingredient, semaglutide, spurs weight loss by mimicking the actions of GLP-1, or glucagon-like peptide-1, a hormone in the brain that regulates appetite and feelings of fullness. 

Once Annie started injecting the drug, she didn’t feel any signs of a suppressed appetite, but developed an extreme aversion to fried foods.

She couldn’t go through a fast-food drive-through with her daughter without feeling sick – which helped her shift a couple of pounds per month.

‘But it wasn’t the huge numbers that you see other people mentioning, that they lost like 10 pounds a month, or six to seven pounds a month. 

‘I think the highest I ever got was like four pounds a month. And then since then, it was one pound a month, two pounds a month a month, many months of no weight loss at all.’

She tried to follow a low-carb, high-protein diet and would go on a brisk walk every day on her lunch break for about 45 minutes. But still, there was no pattern to her weight loss, no hints as to why the medicine might not be working in the same way that it has for so many others.

Today, nearly two years on, she has managed to shift 40 pounds – for which she credits to Mounjaro, which she started taking in July 2023. 

Still, it was a slow process, shifting roughly three pounds per month – far fewer than the six to 10 pounds many people report regularly losing. 

And she was still hungry. Despite the drugs mimicking the hormone that makes a person feel fuller for longer, Annie felt they had not suppressed her appetite. 

Dr Gitanjali Srivastava, an obesity specialist at Vanderbilt University, told Dailymail.com: ‘Oftentimes these patients have very complicated conditions. 

‘There are a lot of factors going on including probably very strong genetics that are at play.’

New York City-based obesity specialist Dr Rekha Kumar [Pictured] told DailyMail.com  that there are so many reasons people eat that are not related to stomach hunger. Emotional eaters, for instance, are more likely to ‘eat through’ the appetite suppressing effects

Annie, for instance, has PCOS, or polycystic ovarian syndrome. This condition runs in families which causes the ovaries to become enlarged and the formation of small cysts on the ovaries, as well as causing hormonal imbalances.

Annie also has hypothyroidism, a condition in which the thyroid gland, which produces and releases hormones that help regulate metabolism, doesn’t make enough of those hormones. 

Hypothyroidism causes a slow response to GLP-1s, according to New York City-based obesity specialist Dr Rekha Kumar. Genetics have been shown to influence a person’s susceptibility to these drugs. Dr Kumar says it’s not just genetics, it’s biology, which includes neural pathways, hormone secretions, and more than just one’s DNA.

Dr Kumar said: ‘Having PCOS, having insulin resistance, having type two diabetes, make patients less responsive, or they tend to lose weight slower because of their biology.

‘I wouldn’t say that they’re necessarily are non responders, but we know across all clinical trials for anti-obesity medicines that people with insulin resistance do respond slower and tend to lose weight slower.’

Doctors say emotional eating, or using food to cope with stress could also be a factor. Even if semaglutide suppresses someone’s appetite, they may still experience cravings or a need for food as a coping mechanism. 

Appetite can rebound after about a year of steady weight loss, too. The body finds a way to counteract the drop in calories a person takes in. 

In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, found that people’s weight loss tends to halt at about 12 months. 

With every 2.2 pounds the study participants lost, their appetite spiked. By the end of the study, participants were still working as hard as they did initially to resist food, but they were only able to cut about 200 calories per day instead of the necessary 800 they aimed for. This reduction in calorie deficit caused their weight loss to plateau.

Dr Kumar said: ‘There are so many reasons people eat that are not related to stomach hunger. 

‘There’s different types of brain circuitry that lead people to eat, cravings, emotional eating. So the underlying way that GLP-1s work might not target the issue that every person has.’ 

Semaglutide, marketed as Wegovy and its sister drug Ozempic, hasn’t worked for about 15 percent of patients taking them, losing less than five percent of their body weight

The above graphic shows how weight-loss drug tirzepatide works. It works to suppress hunger by mimicking hormones indicating that the body is full. It also shows the passage of food through the stomach by reducing the production of stomach acid and contractions of the muscle

The higher the dose the drug, the more extreme the effects are projected to be. 

In addition to suppressing appetite, GLP-1 agonists block the action of glucagon, a hormone that signals the liver to release glucose into the bloodstream, thus increasing blood sugar levels. 

The medicines help the body better respond to changes in insulin, also known as insulin sensitivity.

For about 15 percent of patients, semaglutide simply isn’t what they need. Doctors can prescribe several other options. According to Dr Srivastava, many who switch to Eli Lilly’s Zepbound ‘do beautifully’. 

Many patients stop taking semaglutide because of the side effects, most notably the severe nausea and vomiting, although most people’s experiences with the unpleasant side effects are typically short-lived.

Some people fare much worse, though, coming down with an inflamed pancreas, severe GI distress, and low blood sugar. Ozempic users have even reported losing their hair while taking the drug.

Ever since Ozempic’s and Wegovy’s debuts, patients and many doctors have lauded them as game changers in the field of obesity medicine. And that has led millions of Americans to believe that they’re a cure-all for excess pounds.

Dr Kumar described how discouraged some of her patients become when the weight does not fall off like it does so many others on the drugs.

‘Recently, we’ve been seeing that because of the expectations that people have based on what is presented out there right now. But I always remind people I say, I know it’s upsetting because you think you’re not responding to the miracle drug, but there are other choices.

She added: ‘I think what’s happening is people are hearing about super responders’ success stories from people that may not necessarily need the medicines to begin with, and they’re hoping for a miracle response. And that is rare for any medicine.’