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.

Why Weight Loss Drugs May Not Work

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.

Why it is Important to Identify Non-responders

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.

Alternative Treatment Options

When Ozempic or Wegovy doesn’t yield desired results, there are still many paths to explore:

1. Switching to Another GLP-1 Drug

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.

2. Use of Older Medications

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.

3. Lifestyle Changes

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.

4. Medical Management of Obesity

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.

Why Side Effects of Weight Loss Drug Ozempic May Be a Barrier

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.

Long-term effects of Ozempic or Wegovy on the Brain

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.

For decades, mental health issues were explained as a result of many small genetic risks piling up over time. However, a study led by German scientists has now identified one gene whose specific variants could appear to directly impact psychiatric symptoms, even in the absence of neurological problems. In rare cases, the study suggests, a single faulty gene may be enough to directly cause mental disorders, much earlier tan doctors typically expect.

Scientists studying mutations in the GRIN2A gene found evidence that certain rare variants do not increase the likelihood of mental illness, but they appear to trigger it. This happens due to a clear biological mechanism, often in the beginning of childhood itself. The findings challenge long-held assumptions about how conditions like schizophrenia, anxiety, and mood disorders develop.

The findings are published in journal Molecular Psychiatry. The study describes GRIN2A null variants as the first known example of a single gene directly causing early-onset and even isolated psychiatric disorders, including early-onset schizophrenia.

How An Unexpected Pattern Emerged

The research team, led by Johannes Lemke from the University of Leipzig Medical Center, did not set out to study psychiatric genetics. They were working with a global registry of people diagnosed with GRIN2A-related disorders, most of whom were tested as children for epilepsy or developmental delays.

When the researchers began asking physicians about mental health diagnoses, a striking pattern emerged. Out of 121 individuals with disease-causing GRIN2A mutations, 25 had been diagnosed with psychiatric disorders. Of those 25, 23 carried null variants that completely shut down the gene’s function. In contrast, only 2 of 37 people with missense variants, which alter but do not eliminate the protein, developed mental illness.

To understand how high and unusual this risk was, the team of researchers compared their findings with 21 years of national health records in Finland. This included records of over 5 million people, and the results were stark.

The analysis of this large population showed that by age 12, carriers of GRIN2A null variants showed an 87-fold higher rate of psychotic disorder compared to the general population. Although this estimate was based on just four cases, risks for mood disorders were nearly 12 times higher, and anxiety disorder six times higher.

What stood out most was timing. Schizophrenia typically appears in late adolescence or early adulthood. Anxiety and mood disorders usually emerge in the teenage years or later. In people with GRIN2A null variants, symptoms began as early as ages 8, 10, or 12.

How Does This Gene Operate In Your Brain?

GRIN2A carriers instruction for making a protein known as GluN2A. This is a critical component of NDMA receptors, which help brain cells respond to glutamate, brain's main excitatory chemical messenger.

When GluN2A is missing, these receptors cannot assemble or function normally. This is what leads to disruption in brain signaling that appears to directly drive psychiatric symptoms. Unlike polygenic risk scores that reflect tiny contributions from thousands of genes, GRIN2A null variants remove a key part of the brain's signaling machinery in one decisive step.

Interestingly, people with missense mutations had similar rates of epilepsy and intellectual disability as those with null variants. But when it came to psychiatric illness, only null variants carried substantial risk.

Mental Illness That Comes Without Warning Signs

Six people in the study developed psychiatric disorders without any intellectual disability. Two of them never experienced epilepsy. Without any known family history, these individuals would have never undergone a genetic testing otherwise. Current psychiatric guidelines also do not recommend genetic screening for isolated mental illness. This is because most participants who were initially tested for seizures or developmental delays, cases with only psychiatric symptoms are likely undercounted. The true prevalence may be higher.

A Targeted Treatment Shows Early Promise

Four people with GRIN2A null-related psychiatric disorders were treated with the amino acid L-serine for over a year, at doses up to 500 mg per kilogram daily. All four showed improvement. In one case, hallucinations stopped entirely. Others saw paranoid symptoms resolve, behavioral control improve, or seizures decrease.

L-serine converts to D-serine in the brain, which helps activate NMDA receptors. Boosting this pathway may compensate for the missing GluN2A subunits, offering a targeted approach rather than trial-and-error treatment.

Rethinking Early Diagnosis

More than 80 percent of people with GRIN2A null-related mental illness also had epilepsy at some point, though seizures did not predict who developed psychiatric symptoms. In most cases, mental illness appeared after epilepsy had resolved.

The findings suggest genetic testing could eventually become part of evaluating early-onset psychiatric disorders. For a small but significant group of patients, the cause of mental illness may be clearly identifiable, biologically grounded, and potentially treatable.

For most people living with mental disorders, the origins will remain complex. But this research shows that, sometimes, the answer may lie in a single gene.

Four-year-old Sienna Dunion had initially flu-like symptoms, however her condition rapidly worsened, leading to a coma. What seemed like a simple flu was actually Acute Necrotising Encephalitis (ANE), a rare and severe brain disorder. After undergoing multiple surgeries and having removed 60% of her intestines, she is now struggling to walk and talk like from before.

How Did It Begin?

The first indication, which was very easy to miss was when she asked to return home five minutes after heading out to play with her scooter, reports The Independent. She had always been happy and exciting, so for her to return home so soon was not normal. She had also complained about feeling "cold and chilly" to her older sister, however, all of such symptoms were just seen as a common cold or flu signs.

As a result, her parents, Gary and Angelina Dunion, decided to keep her off school on Monday 17 November. Her temperature raised, no one was really concerned. All of these were cold and flu symptoms. She was still playing with her Barbies.

But it was on a Wednesday morning when she became unresponsive and had to make an emergency trip to A&E in Kettering. This is when she was induced into coma and diagnosed with the rare brain disease ANE.

Three weeks later, her family is facing the challenges to cope with the new changes which may take away how her daughter was before. Now, she requires years of intense rehabilitation to learn how to walk and talk again.

What is Acute Necrotising Encephalitis (ANE)?

Acute necrotizing encephalopathy (ANE) is a rare and serious brain condition that can cause sudden and rapid neurological decline after a viral infection, most often the flu or COVID-19. Because only a small number of cases have been reported worldwide, there is no standard treatment, making diagnosis and management especially difficult.

Sienna's father told The Independent, "For us, it’s really important that people can understand this has happened to a really healthy four-year-old girl who had no underlying issues. It has completely changed our lives overnight. What started as a flu has turned into a complicated brain disease and the last three weeks have just been horrendous.”

A Rare Diagnosis, But Urgent Care

Sienna had been feeling unwell on Monday and Tuesday, but it was on November 19 that her condition suddenly worsened. Her mother, Mrs Dunion, became alarmed when she tried to wake her and realised Sienna was unresponsive.

At A&E, doctors initially believed she was dehydrated after she tested positive for influenza. However, a CT scan showed unusual findings, including white lesions, while other test results remained unclear.

By 11 pm, doctors decided Sienna needed to be moved to the intensive care unit at Nottingham’s Queen’s Medical Centre. An MRI scan later confirmed a diagnosis of acute necrotising encephalopathy (ANE), a rare condition linked to viral infections.

Because of how uncommon the disease is, doctors designed a personalised treatment plan for her. This included plasma exchange, a procedure her family described as effectively washing her brain.

On Saturday, November 22, an ultrasound revealed a large build-up of fluid in her stomach. Sienna had to undergo emergency surgery, during which 60 per cent of her intestines were removed. Her father called it the hardest night of his life.

She later needed two more surgeries after air was found in her abdomen. Sienna now has a stoma bag and will live with short bowel syndrome for the rest of her life.

“The one thing doctors have been clear about is that she will not be the same when she fully wakes up,” Mr Dunion said. “She will need extensive rehabilitation.”

Although Sienna is awake, her father explained that she does not understand what is happening around her. She is weak, struggles to track with her eyes, and cannot eat on her own. The family is now fundraising to support her rehabilitation, including physiotherapy, speech and language therapy, feeding support, and changes needed at home.

A family struggling to cope

The couple also have a seven-year-old daughter, who is very close to Sienna. “They are best friends,” Mr Dunion said. “She keeps asking, ‘Where is Sienna? When can we be a family again?’”

He added that it is impossible to explain the seriousness of the situation to her. “I can’t tell her that she won’t be able to talk to her sister for a long time.”

“She was the most caring, easygoing four-year-old I’ve ever known,” her father said. “Even when she had a fever, she would check our temperature to make sure we were okay.”

He described her as a social child who loved being around other kids and had an infectious belly laugh. “We just don’t know if we’ll hear that laugh again,” he said.

The last thing anyone hopes to unwrap this Christmas is a heavy dose of flu. Yet as hospital admissions linked to the virus climb to levels not seen since 2010, this winter’s flu surge has pushed the NHS into what officials are calling a “worst-case scenario.”

Infections have jumped by over 50 per cent in just one week, and health leaders say there is still no clear peak. On average, 2,660 people a day were occupying hospital beds with flu last week, the highest figure ever recorded for this point in the season. Data from the UK Health Security Agency show the highest infection rates among children aged five to 14, followed closely by young people between 15 and 24. A number of schools have temporarily closed to curb outbreaks, while NHS leaders have advised people to consider wearing masks at work or on public transport, echoing guidance seen during the Covid years.

What Is Super Flu?

The strain driving the current spike has picked up the nickname “super flu” because it is believed to be a mutated form of influenza A (H3N2), known as “subclade K.”

Influenza H3N2 does not circulate as often as some other flu strains. Dr Simon Clarke, associate professor of cellular microbiology at the University of Reading, explains that the letters “H” and “N” refer to two proteins found on the virus surface, haemagglutinin and neuraminidase. “The numbers simply tell us which versions of those proteins are present,” says Dr Clarke. “It’s a way of grouping strains. This year, H3N2 happens to be the one in the lead.”

“H3 subtypes are relatively uncommon,” he adds. “That means fewer people have built up immunity. There is also evidence they spread more easily and mutate faster, which makes them harder for vaccines to keep up with.

“What we are seeing now is the outcome of that: cases rising sharply earlier than usual, with numbers likely to climb further as winter goes on.”

How Does Super Flu Differ From The Usual Variety?

Broadly speaking, flu falls into three main groups, A, B and C, according to Professor Ed Hutchinson from the Glasgow Centre for Virus Research. “Types A and B are the ones that make people seriously ill each winter. Influenza C circulates too, but it rarely causes severe disease. They are related, but not closely enough that immunity to one protects against the others,” he explains.

The concern is not that the virus has suddenly become far more deadly. Many people will catch it and recover without major problems. “The issue is scale,” Hutchinson says, as reported by The Telegraph. “When a virus spreads widely, even a small proportion of severe cases quickly adds up. That is what puts pressure on individuals and on the NHS.”

Last week, around 1,700 flu patients were in hospital, a 63 per cent increase on the previous week and more than 50 per cent higher than the same period last year. This rise is partly linked to a particularly aggressive subtype of the circulating H3N2 virus. “This strain is appearing earlier and spreading faster than we would expect, and immunity levels in the population are lower than usual for this stage of the season,” says Dr Aslam.

Is The Flu Shot Effective Against Super Flu?

Recent figures suggest the flu vaccine cuts the risk of hospital admission by roughly 30 to 40 per cent in older adults. That protection rate is lower than for some other vaccines, but it is in line with flu vaccine performance in past years. For that reason, advice has not changed. Vaccination remains the single most effective step people can take to protect themselves and to ease pressure on the NHS.

Why Does The Vaccine Have Different Effectiveness In Different Age Groups?

This season’s vaccines are still doing a solid job of preventing severe illness. Vaccinated children are about 70 to 75 per cent less likely to need a hospital visit or admission for flu. Among adults, the reduction is closer to 30 to 40 per cent.

One reason for this gap is the type of vaccine used. Children receive a nasal spray, while adults are given an injection. Research shows the nasal spray works particularly well in children but is less effective in adults, which is why different recommendations exist. So the comparison reflects not just age, but also different vaccines.

Another factor is prior immunity. Adults have encountered many flu viruses over their lifetime, so the added benefit of each new vaccine dose may be smaller than it is for a child. Even so, that extra protection still matters and can make a real difference.