Why 15% don’t lose weight on Ozempic—’non-responders’ identified

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By Creative Media News

  • Ozempic’s weight loss success faces resistance in 15% of patients
  • Genetic, hormonal, and lifestyle factors contribute to non-responsiveness
  • Patients report varied responses and side effects with Ozempic use

Ozempic and comparable fat-burning injections have been a boon for the millions of obese Americans. 

A minimum of 5.6 million individuals in the United States have been prescribed the injection to reduce their body mass and, by doing so, their risk of a variety of diseases by 20%. 

According to large-scale clinical trials, the medication, which functions by inhibiting appetite signals, may assist patients in losing as much as 15 percent of their body weight in just over a year. 

However, while some patients may experience significant weight loss success, one in every six patients fails to lose any weight or loses so little that the difference is hardly perceptible. 

Certain physicians have begun to refer to this inquisitive cohort as “Ozempic non-responders.” 

This patient population perplexes specialists, as some individuals gain weight but soon reach a plateau, whereas others barely experience any weight loss. 

Prominent medical professionals posit that the ineffectiveness of the best-selling medication may be attributed to a confluence of factors including genetic predisposition, thyroid disorders, and diet. 

Approximately 15% of patients in clinical trials for similar medications (Ozempic, Zepbound, Mounjaro) fail to respond, losing less than 5% of their body weight over 68 weeks. 

A five percent loss, or twelve and a half pounds, for a 250-pound male taking the drugs, is significantly less than the study average of fifteen percent loss, or 37 pounds. 

Since the conclusion of those clinical trials, some individuals, including several Reddit users, have reported gaining weight on the medications; one individual claims to have acquired 13 pounds. 

TikTok user Shelly ultimately increased her Ozempic dosage to its maximum for five months but to no avail. 

“It did quiet the food noise; I no longer felt as though I was constantly thinking about food, but I did not lose any weight.” ‘While I was able to consume normally, I developed severe acid reflux that I no longer desired.’ 

She expressed disappointment that despite taking the medication to reverse the weight gain caused by a leg injury, she has not yet lost any of the weight. However, she suffered from severe acid reflux. 

She has ceased using a weight loss medication and has commenced engaging in vigorous physical activity, particularly lifting hefty weights. 

Viola, an additional TikTok user, remarked, “I have no idea why it isn’t working for me; in fact, it’s leaving me hungry.” 

Katherine, an additional TikToker, stated, “I used Wegovy, which contains the same ingredient as Ozempic, for four to five months with no loss.” I maintained a solid stance. 

“I’m simply maintaining; I’ve been fluctuating between four and five pounds; I basically don’t fall below a certain number; and I simply continue to bounce back and forth.” 

She further expressed her frustration regarding the plateau, particularly considering her lifelong struggle with weight management. 

Additionally, a user on the drug’s Reddit commented, “Since I began taking Mounjaro in September of last year, I have lost thirty pounds in five months.” I was required to transfer to Wegovy in February. I was initiated on the second-lowest dose and gradually increased to 2.4. Five pounds have been added to my weight since February… Neither do I experience appetite suppression. 

After the birth of her first child, Annie, who weighed 198 pounds in May 2022, had struggled with her weight for years and discovered that nothing worked to help her lose it. 

Annie reported being “extremely receptive” when she brought up the subject of taking the medications during a doctor’s appointment. 

Similar to Annie, the physician was a South Asian woman who had a familial predisposition to diabetes, which meant she could relate to her patient’s concerns

Annie was ecstatic. She had witnessed accounts of individuals who had lost twenty to thirty pounds and believed she was on the verge of discovering a treatment for her obesity; the individual assured her that she would recover in time to spend with her family. 

Although she did not encounter the intense nausea that is commonly reported, she also failed to observe any immediate benefits. 

Mounjaro, Wegovy, and Ozempic are agonists of the GLP-1 receptor. By replicating the actions of GLP-1, or glucagon-like peptide-1, a hormone in the brain that controls appetite and feelings of fullness, their active ingredient, semaglutide, promotes weight loss. 

Annie did not experience any symptoms of appetite suppression after she began injecting the drug; however, she developed an intense aversion to fried foods. 

Because she felt ill while completing a fast-food drive-through with her daughter, she was able to lose a few pounds each month. 

However, it was not the exorbitant figures that others mention, such as losing six to seven pounds or ten pounds per month. 

“I believe the highest I ever achieved was around four pounds per month.” Thereafter, the monthly weight loss was between one and two pounds, with many months passing with no weight loss. 

She attempted to adhere to a low-carb, high-protein diet and would walk briskly for approximately 45 minutes during her daily lunch break. Nevertheless, her weight loss lacked any discernible pattern and did not indicate why the medication might not be functioning in the same manner as it has for countless others. 

Presently, after almost two years, she has successfully lost forty pounds; she attributes this accomplishment to Mounjaro, a program she commenced using in July 2023

Nonetheless, the process was gradual, averaging around three pounds per month of weight loss—considerably less than the six to ten pounds that many individuals claim to lose regularly. 

Moreover, she remained ravenous. Annie believed that despite the medications simulating the hormone responsible for prolonged satiety, they had not effectively inhibited her appetite. 

Obesity specialist at Vanderbilt University, Dr. Gitanjali Srivastava, said, “Frequently, these patients have extremely complicated conditions.” 

“There are numerous factors at play, including very strong genetics,” the speaker speculated. 

For example, Annie is afflicted with polycystic ovarian syndrome (PCOS). Hereditary in nature, this disorder manifests as ovarian enlargement accompanied by the development of small cysts, in addition to inducing hormonal imbalances. 

Annie also has hypothyroidism, a condition characterized by insufficient production of hormones that aid in metabolism regulation by the thyroid gland, which is responsible for their production and release. 

A sluggish response to GLP-1s is the result of hypothyroidism, according to obesity specialist Dr. Rekha Kumar of New York City. There is evidence that an individual’s susceptibility to these substances is influenced by genetics. It is biology, not genetics, according to Dr. Kumar, which encompasses neural pathways, hormone secretions, and more than just DNA. 

According to Dr. Kumar, patients with PCOS, insulin resistance, or type 2 diabetes are typically less responsive or shed weight at a slower rate due to biological factors. 

“I would not say they are non-responders, but we know that people with insulin resistance respond and lose weight more slowly to anti-obesity medications across all clinical trials.” 

According to physicians, emotional eating or the use of food as a coping mechanism may also play a role. Despite the appetite-suppressant effects of semaglutide, individuals may still encounter cravings or a compulsion for food as a means of coping. 

Additionally, after about a year of consistent weight loss, appetite may return. The human body devises a mechanism to compensate for the reduction in caloric intake. 

Kevin Hall, a National Institutes of Health researcher specializing in measuring metabolism and weight change, discovered in a recent study that weight loss typically ceases around 12 months in. 

An appetite increase was observed in study participants for every 2.2 pounds lost. Participants maintained the same level of effort to resist food until the conclusion of the study; however, their daily caloric reduction was only approximately 200, as opposed to the intended 800. The cessation of their calorie deficit led to a plateau in their weight loss. 

There are numerous reasons why people eat that are not related to stomach hunger,” said Dr. Kumar. 

Eating is influenced by various forms of brain circuitry, including cravings and emotional eating. Therefore, the fundamental mechanism by which GLP-1s function may not address the specific issue that each experiences. 

It is anticipated that the effects will become more extreme as the dosage of the substance increases. 

GLP-1 agonists increase blood sugar levels by inhibiting the action of glucagon, a hormone that instructs the liver to secrete glucose into the circulation, in addition to suppressing appetite. 

Medications improve the body’s sensitivity to fluctuations in insulin, a condition referred to as insulin sensitivity. 

Approximately 15% of patients do not require semaglutide for whatever reason. Others may be prescribed by physicians. Many individuals who transition to Eli Lilly’s Zepbound, according to Dr. Srivastava, “do beautifully.” 

Numerous patients discontinue semaglutide due to its adverse effects, particularly severe nausea and vomiting. However, it is important to note that the majority of individuals encounter these distressing side effects for a brief duration.

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However, some individuals fare considerably worse, developing pancreatic inflammation, severe gastrointestinal distress, and low blood sugar. Hair loss has been reported by Ozempic users while on the medication. 

Since their introductions, patients and numerous physicians have hailed Ozempic and Wegovy as revolutionary products in the field of obesity medicine. As a result, millions of Americans have concluded that they are a panacea for surplus weight. 

Dr. Kumar described how disheartened some of her patients become when they fail to lose weight as rapidly as so many others who are taking the medication do. 

Recently, this has become apparent because people’s expectations are predicated on what is presently presented. However, I consistently reiterate to individuals that while it may be disheartening to find oneself not responding to the miracle medication, alternative courses of action do exist. 

Further, she stated, “I believe that people are hoping for a miraculous response after hearing about the success stories of super responders who may not have needed the medications to begin with.” And such an occurrence is uncommon in the field of medicine.

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