When Ozempic And Wegovy Fail To Work- Why GLP-1 Drugs Aren’t The Magic Bullet For Everyone
Ozempic and Wegovy have received a lot of publicity as revolutionizing treatment options for obesity. Both medications form a class of GLP-1 receptor agonists, which mimic a hormone in the body called glucagon-like peptide-1 and are involved in the regulation of appetite and blood sugar. Indeed, in initial clinical studies, the majority of those on the drugs lost 15% to 22% of body weight, hence much optimism. For most patients, these medications are underwhelming for about 20% of patients due to minimal weight loss or other challenges.
Take a closer look at why the weight loss drugs may not work for everyone, together with what options exist when they don't deliver the expected outcomes.
While GLP-1 receptor agonists have produced phenomenal responses in a majority of patients, it remains a reality that these drugs work differently for different people. Here's why:
1. Genetic and Hormonal Variability
Weight loss medications interact with complex systems in the body that differ from person to person. Genetics, hormones, and individual brain responses to energy regulation play significant roles in determining how a person responds to drugs like Ozempic and Wegovy.
2. Underlying Medical Conditions
Other conditions, such as sleep apnea, may be prevalent and prevent or delay the achievement of weight loss goals. Prescription drugs like antidepressants, steroids, or contraceptives are other medications that can nullify weight loss medication benefits.
3. Unrealistic Expectations
Often, they come to these medications with enormous hopes; expecting the promised rapid and dramatic weight loss. Progress creates disappointment if it has not stalled. In patients who rigidly follow recommended lifestyle modifications, frustration and disappointment are most common.
For most patients, the effectiveness of GLP-1 receptor agonists is evident within a few weeks of treatment. Weight loss typically begins within a few weeks of initiating therapy and tends to increase with dosage. However, some patients respond very little, if at all, despite strict adherence to their regimen.
For nonresponders, this can feel like a dead end. However, understanding the unique complexities of obesity is essential. This condition stems from brain dysfunction, and the pathways that contribute to weight regulation differ among individuals.
When Ozempic or Wegovy doesn’t yield desired results, there are still many paths to explore:
For example, some patients who don't respond well to one GLP-1 receptor agonist might find success with another drug in the same class. Newer medications, such as Zepbound, target other hormone pathways and seem promising even for those not responsive to earlier drugs.
While there is much to say about newer drugs, older treatments can still be useful and work for some patients. One can also seek the help of a medical provider specializing in obesity treatments in order to identify the best alternatives.
Diet, exercise, sleep, and stress management continue to be integral components of any weight loss program. New changes may be small but can make an enormous difference in one's health and success.
It is a complex disorder, and most patients should receive a multidisciplinary treatment. Collaboration with an obesity-aware doctor may mean access to tailored treatment plans, ranging from psychological support all the way to metabolic testing, and many others.
For others, side effects like nausea, vomiting, or diarrhea hinder them from continuing with these drugs. These symptoms often reduce as the body becomes accustomed, but for some, they might be severe enough to stop treatment altogether. In those instances, alternative drugs or procedures become vital to find.
Another largely unexplored area relates to GLP-1 drugs' long-term effects on the brain's regulation of hunger and satiety. Although GLP-1 drugs suppress appetite and can lead to effective weight loss, emerging research suggests that they may also affect brain reward mechanisms, changing the way patients experience foods.
This aspect could prove of paramount significance in the future treatment of obesity. Perhaps GLP-1 receptor agonists do indeed affect and rewire the brain's reward pathways and will thus provide sustained benefits beyond discontinuation. However, more research is required to understand this phenomenon fully.
While for many, Ozempic and Wegovy have revolutionized obesity treatment, these are certainly not a one size fits all. Nonresponders need not lose hope- alternative strategies and medications abound. A consultation with an obesity expert healthcare provider is essential to put together a comprehensive, tailored treatment plan.
The route toward effective weight loss may be challenging, but with the evolution of obesity medicine and a better understanding of individual needs, there is a path forward for everyone.
Credit: NYU Langone/iStock
Indians are facing an increasing burden of heart diseases, and mortality is rising faster compared to other countries. A top US cardiologist has now shared the major risk factors that range from genetics to obesity to pollution.
Cardiovascular diseases (CVDs) cause nearly 31 per cent of all deaths in India, according to the latest Sample Registration Survey (SRS) 2021-2023 data from the Registrar General of India, released in September 2025.
The SRS report highlighted cardiovascular diseases as the leading cause of death, especially among adults over 30.
Speaking exclusively to HealthandMe, Dr. Sripal Bangalore, Professor of Medicine at New York University School of Medicine, highlighted the key reasons why India is seeing a huge burden of heart diseases.
"I think it’s a combination of traditional and non-traditional risk factors. Globally, we are seeing the burden of obesity increasing, and specifically in India, genetic factors and non-traditional risk factors also play a role," Dr. Sripal said.
"There is a growing investigation into lipoprotein(a) and other causes of cardiovascular disease (in India). Obesity is a major risk factor, and I’m sure stress and pollution also add to it, with more and more data supporting these links," he added.
Data from the World Heart Federation showed that heart disease kills 28.6 lakh Indians every year. In the recent past, India has also been seeing a significantly higher rate of heart attacks and related deaths, even in children as young as 12 years old.
Also read: AHA’s New Dyslipidemia Guidelines Stress Early Screening, Lifestyle Management
"I think we need to know that part of it tends to be non-traditional, because in the Western world most of it is explainable by traditional risk factors like hypertension, diabetes, and hypercholesterolemia," Dr. Sripal said.
"What we see in India is that it is less about those risk factors, but more about non-traditional ones, including potentially genetic factors and lipoprotein(a)," the doctor added.
The Indian-origin interventional cardiologist also cited lifestyle factors such as stress and pollution that are significantly adding to the increased risk of cardiovascular events in the country.
Recently, the American Heart Association (AHA) released cholesterol guidelines, which stressed the importance of early screening, starting with teenagers.
The guidelines call for early intervention through early screening and healthy lifestyle changes, starting from childhood.
It recommends:
"India is a good example where LDL levels (bad cholesterol) may not be very high, like in the Western world. Many times, HDL cholesterol (good cholesterol) tends to be lower, and there are other risk factors, including lipoprotein(a), which seems to be elevated here," Dr. Sripal said.
The doctor also explained whether overall diet quality matters more than just cholesterol intake.
"Diet adds to the totality of everything that we do, including increasing the risk of obesity. Cholesterol may explain some part of it, but having a heart-healthy diet is critically important," Dr. Sripal said.
The cardiologist highlighted the need to increase the intake of fruits and vegetables, as consuming natural foods is critically important.
Importantly, he also emphasized at least making sure that you have a lipid panel to check your cholesterol levels.
"We are assuming that you are staying healthy and not smoking. Checking blood pressure, it depends on your age, but at least once a year, checking your lipid panel would be critically important," Dr. Sripal told HealthandMe.
As a cardiologist, he shared that to boost heart health, the key is
"Pollution is one factor, and I think we can all do our part to make sure that we don’t contribute more to environmental pollution," he noted.
Credit: Toxic Link
While India’s Ministry of Environment, Forest, and Climate Change (MoEFCC) enforced a nationwide ban on identified single-use plastic (SUP) items from July 1, 2022, a new survey showed that violations continue to persist across major cities in the country, raising significant health and environmental risks.
The survey of 560 locations by Toxics Link -- an Indian environmental research and advocacy organization -- showed that 84 percent of sites across Delhi, Mumbai, Guwahati, and Bhubaneswar still use or sell banned plastic items.
Bhubaneswar recorded the highest availability of banned SUPs at 89 percent of survey locations, followed by Delhi at 86 percent, Mumbai at 85 percent, and Guwahati at 76 percent.
The survey noted that high use among street food vendors, juice shops, coconut water sellers, vegetable vendors, and ice cream parlours.
"The continued presence of banned plastic items in a majority of locations suggests that enforcement remains inconsistent,” said Ravi Agarwal, Director of Toxics Link.
“Unless implementation improves and the supply of these products is controlled, the ban will not effectively address plastic littering and pollution,” he added.
Plastic carry bags, disposable plastic cutlery, cups, plates, and straws often contain chemicals like BPA and phthalates, which can interfere with the body’s hormonal balance.
BPA is an industrial chemical used to make certain plastics and resins, and its exposure has been linked to several health conditions, including an increased risk of high blood pressure.
Phthalates, another group of chemicals used to make plastics more flexible, have been found to disrupt the endocrine system, leading to potential health issues.
Also read: Your Kids’ Fast-fashion Clothing May Be Laced With High Levels of Toxic Lead
Studies have proven that BPA and phthalates can mimic the body’s hormones, particularly estrogen. This interference can disrupt the normal functioning of the cardiovascular system, leading to increased blood pressure.
Plastics also contain some highly toxic chemicals, such as flame retardants, per- and polyfluoroalkyl substances (PFAS), that can migrate into the environment and into human bodies.
According to a report by WWF, an average person could be ingesting approximately 5 grams of plastic every week.
Scientific studies have proven that the health effects of plastics include cancer or changing hormone activity (known as endocrine disruption), which can lead to reproductive, growth, and cognitive impairment.
Recent evidence also indicates that humans constantly inhale and ingest microplastics through contaminated seafood, including fish and shellfish.
In addition, microplastics have been found in tap water, bottled water, and even commonly consumed beverages, such as beer and salt.
The UNDP urges individuals, organizations, and governments to work together to
Other options include
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While a weakened immune system and fear of complications once denied people with HIV access to organ transplants, doctors at a Delhi hospital have now challenged the idea with a successful kidney transplant surgery on a 43-year-old HIV-positive patient from Ethiopia.
According to the team of doctors from the Max Super Speciality Hospital, Patparganj, who successfully performed the complex living donor kidney transplant, advancements in antiretroviral therapy and transplant protocols have made such procedures increasingly safe in carefully selected cases.
“HIV is no longer a barrier to organ transplantation when managed appropriately,” said Dr. Ravi Kumar Singh, Senior Consultant, Nephrology and Transplant Physician at Max Hospital, Patparganj.
“With strict selection criteria and coordinated multidisciplinary care, patients with well-controlled HIV can achieve outcomes comparable to the general transplant population.”
Also read: India Identifies 219 Districts As Priority For Intensified HIV/AIDS Interventions
The patient, who had been living with HIV for 10 years, developed end-stage renal disease 3 years ago and has been dependent on regular dialysis since then.
Before the surgery, the patient underwent extensive evaluation to ensure optimal control of HIV, including a stable immune profile and undetectable viral load.
The patient’s 33-year-old wife donated one of her kidneys. Compatibility testing confirmed matching blood groups and a negative cross-match, enabling the team to proceed with the transplant.
“Kidney transplantation in patients with HIV requires a highly meticulous and coordinated approach, given the complexities of balancing immunosuppression with ongoing antiretroviral therapy,” said Dr. Paresh Jain, Senior Director, Urology, Robotic Surgery & Renal Transplant.
“In this case, careful pre-transplant evaluation, precise surgical execution, and close post-operative monitoring were critical to ensuring a successful outcome. This procedure reflects how advances in transplant science and surgical expertise are enabling us to safely expand access to life-saving transplants for patients who were once considered high-risk,” he added.
Following the transplant, the patient has shown encouraging recovery, has been taken off dialysis, and is gradually returning to normal daily activities, the doctors said. The patient also continues on a carefully monitored regimen of immunosuppressive and antiretroviral therapy, they added.
Also read: India's Silent Crisis: Why We Must Embrace Deceased Donor Organ Transplantation
With advancements in antiretroviral therapy (ART), enabling people to live longer, HIV has now become a chronic, manageable condition. However, the HIV positive patients are now more likely to die from end-stage organ disease than from AIDS-related infections.
As per the US National Institutes of Health, people with HIV can successfully donate or receive transplanted organs with reasonable success rates.
However, health care providers must consider and monitor potential drug interactions, kidney and liver function, and HIV viral suppression in people with HIV receiving a transplant.
Further, the NIH advised HIV positive patients to continue taking all prescribed HIV medicines before and after transplant.
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