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.
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Harry Potter star Daniel Radcliffe has quit smoking after 20 long years. The reason: his two–year–old son with girlfriend Erin Darke.
Speaking to media outlet Vulture, the 36-year-old English actor shared that after becoming a father, he was inspired by intrusive thoughts about his mortality, which enabled him to quit the deadly habit after two decades.
"I smoked for 20 years pretty heavily, and I was never even thinking about quitting, and then shortly after having my son, the intrusive thoughts of my own death really helped as an incentive to quit," Radcliffe was quoted as saying.
Radcliffe also shared how a book -- The Easy Way to Quit Smoking, by Alan Carr -- helped him decide to quit smoking.
"It may not work for everybody, but it really worked for me," noted the star, currently starring in the Broadway play Every Brilliant Thing.
Earlier this month, the actor spoke with WSJ Magazine and shared that from being on “cigarettes all day”, he's transformed into a fitness freak.
Smoking can affect all organs in our body. While lung cancer and tuberculosis are the most prominent ones, smoking can seriously increase the risk of several chronic diseases. These include:
While quitting tobacco is important, it is a difficult task, with some people finding it harder to quit than others. It may be important to seek help quitting.
Also read: Cigarettes And The Female Body: The Hormonal Toll We Don’t Talk About
These strategies have shown varying levels of success in aiding smokers to quit permanently. In addition, alternative methods like e-cigarettes and mindfulness-based techniques have gained traction in helping reduce smoking addiction.
Behavioral Support
Quitting smoking isn’t just about resisting cravings. Often, behavioral support through counseling or therapy is crucial for tackling the psychological aspects of addiction. Behavioral therapy involves working with a trained professional to identify triggers, develop coping strategies, and create a tailored quit plan. Research shows that combining counseling with other quit methods can significantly increase success rates.
Prescription Medications
Some medications, such as varenicline (Chantix) and bupropion (Zyban), have been shown to help people quit smoking by reducing cravings and withdrawal symptoms. Experts suggest that varenicline works by blocking the effects of nicotine in the brain, while bupropion is an antidepressant that helps manage withdrawal symptoms. Both medications are generally more effective when combined with behavioral therapy.
Nicotine Replacement Therapy (NRT)
Nicotine replacement products, such as nicotine patches, gums, lozenges, and nasal sprays, deliver controlled amounts of nicotine to ease withdrawal symptoms. According to experts at Harvard Health, NRT can double the chances of quitting by alleviating physical cravings while the person works on overcoming the psychological addiction.
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About 10.6 percent –15 percent of India's population suffers from some form of mental health conditions, with 15 percent of the adult population also requiring active intervention.
To enable researchers to gather as well as systematically document data on patients with major forms of mental illness, neuroscientists in India have developed CALM-Brain — a digital repository of data on brain structure and function from a range of psychiatric disorders.
CALM-Brain contains data from over 2,000 participants from 900 families across the country.
CALM-Brain will help clinicians and researchers
“CALM-Brain was conceived as a method to assemble data from multiple scales of analysis of brain structure and function on a single platform. We believe that the application of modern methods of data analysis to this dataset will help bridge the gap between these scales of analysis,” said Prof. Raghu Padinjat, CBM co-ordinator at CBM-NCBS, in a statement.
Also read: World Happiness Report 2026 Flags Social Media Harms On Adolescents' Mental Well-being
CALM-Brain is the result of collaborative efforts of researchers at the Rohini Nilekani Centre for Brain and Mind (CBM) — a partnership between the National Institute of Mental Health and Neuro Sciences (NIMHANS) and the National Centre for Biological Sciences (NCBS) - TIFR.
CALM-Brain is India’s first-of-its-kind repository of clinical, neuroimaging, behavioral, genetic, and other datasets on disorders such as:
The dataset is also linked to a biorepository of stem cells, which can be used to perform biological research in psychiatry to understand the origins of such severe mental illnesses.
“The primary goals of the project are to identify biological markers of severe psychiatric illnesses, which cut across traditional diagnostic frameworks. In addition, we will try to identify fundamental biological mechanisms of the disease and medication response,” said Prof. Y.C. Janardhan Reddy, CBM coordinator at CBM-NIMHANS.
Mental wellness is a major health and economic concern in India. The World Health Organization (WHO) estimates India’s economic loss due to mental health conditions to be USD 1.03 trillion (2012-2030).
Recently, health experts and policymakers, as part of the government-led Post-Budget Webinar series, highlighted the growing burden of mental and neurological disorders in India and also stressed the urgent need to strengthen institutional capacity to meet emerging healthcare demands.
"One in seven Indians is affected by mental health disorders, while several states continue to face a treatment gap ranging from 70 to 90 percent," the experts said.
They added that "neurological and mental health conditions are among the leading contributors to disability-adjusted life years (DALYs)" among citizens.
To address the rising burden, the government aims to launch NIMHANS-2 — first announced by Finance Minister Nirmala Sitharaman during the Union Budget 2026-27 — to deliver specialized care for mental health and neurological disorders in north India.
"In addition, the Central Institute of Psychiatry, Ranchi, and the Lokopriya Gopinath Bordoloi Regional Institute of Mental Health, Tezpur, will be upgraded as regional apex institutions to strengthen mental healthcare services in the eastern and north-eastern regions," FM Sitharaman said.
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Metformin has remained the safe and most effective first-line treatment for Type 2 diabetes for the last 60 years. The anti-diabetic drug has been known to work through the liver and gut to lower blood sugar levels and improve the way the body handles insulin.
However, a new study has, for the first time, shown that metformin probably works through the brain, and neurons in a specific region boost its anti-diabetic effects.
The findings open up potential for more targeted and effective diabetes therapies as well as for improving brain health.
The international team of researchers led by those at Baylor College of Medicine, in the US, decoded a brain-based pathway involved in metformin's ability to lower blood sugar.
They found that the widely used diabetes medication switches off a key protein and activates specific neurons, and lowers blood sugar through a previously hidden pathway.
"Metformin is not just working in the liver or the gut, it's also acting in the brain. We found that while the liver and intestines need high concentrations of the drug to respond, the brain reacts to much lower levels," said corresponding author Dr. Makoto Fukuda, associate professor of pediatrics - nutrition at Baylor.
The new study, published in Science Advances, targeted a small protein called Rap1 -- located in a brain region known as the ventromedial hypothalamus (VMH).
Mice studies proved that metformin fights blood sugar by suppressing the activity of Rap1 in VMH.
To prove the findings, the team deployed genetically engineered mice without Rap1 in the brain.
In mice with a high-fat diet that models type 2 diabetes, low doses of metformin did not improve their blood sugar levels.
On the contrary, when metformin was delivered in very small amounts directly into the brains of diabetic mice, it effectively lowered blood sugar levels.
Further, the team found that SF1 neurons located in the VMH are helping metformin to fight diabetes.
When the team measured the electrical activity of these neurons, they found that metformin’s activity increased only when Rap1 was present
The findings demonstrated that Rap1 is required for metformin to activate these brain cells and regulate blood sugar.
"This discovery changes how we think about metformin," Dr. Fukuda said.
Also read: Indian Drug Regulator Flagged 90 Combination Medicines Sold Without Approval
Metformin has also shown potential to boost fertility levels in people with polycystic ovary syndrome (PCOS) -- a condition that affects how the ovaries work.
Metformin treats PCOS by lowering insulin and blood sugar levels. This can also improve ovulation and encourage regular periods.
Metformin has previously shown its potential for slowing brain aging and improve lifespan.
While metformin is safe for most adults and children aged 10 years and older, the drug may not suitable for some people. this includes people who:
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