Category: Metabolic Disorders

South Africa’s Weight-loss Revolution is Testing Medical Discipline

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One in every two South African adults is considered overweight or obese. It is not surprising, then, that potentially lifesaving prescription-based metabolic medicines are surging in popularity. The challenge: demand is rising faster than the clinical structure needed to support it, leaving many patients unsure what responsible, medically supervised care should look like.

It is a concern Dr Gerhard Vosloo, a prominent sports, exercise, and lifestyle physician, says he is encountering more frequently in clinical practice. “Expectations are becoming unreasonably high, while few understanding the level of medical oversight required to manage these therapies responsibly. It’s just not as simple as prescribing an aggressive regime and standing back.”

To address issues in today’s weight management sector, Dr Vosloo established Dr GL Vosloo Medical Practice, managed by BioWell, as a formal online medical practice built around sound clinical judgment, structured care, and meaningful patient oversight. He says, “We’re building a model – one that could serve as a stable structure for the wider industry, where sound medical judgment is consistently prioritised over the public’s growing appetite for weight loss drugs.”

The danger of normalising prescription therapy

Dr Vosloo cautions that the rapid rise of these medicines in the mainstream is oversimplifying a highly complex subject and making pharmaceutical use seem routine, when it should remain a final option after disciplined nutrition- and exercise-led approaches have been fully explored.

“Misinformation spreads like wildfire online. People are starting to view prescribed medicines as a routine diet option, when they should be a last resort. Pharmaceuticals are powerful tools for people who struggle to lose weight, but they should be introduced only when medically appropriate, and only after nutrition, exercise, and appropriate supplementation have been fully explored.”

He maintains that prescribed medicines should form part of a structured metabolic management programme that, when used correctly, will reduce cardiometabolic risk, improve insulin sensitivity, regulate appetite, and support meaningful body composition change. The goal is to improve metabolic health under disciplined supervision, and when treatment is not medically necessary, doctors must refuse to prescribe.

“Clinical eligibility must be determined by medical rationale,” he says. “A patient’s preference for medication, emotional pressure to start treatment, or the ability to pay cannot override clinical judgement. Where medical need is absent, a BioWell doctor will decline to prescribe and direct the patient to a non-pharmaceutical, doctor-supported metabolic management pathway.”

Dosing with discipline

Beyond unnecessary prescribing practices, Dr Vosloo stresses that the industry is undermined by over lenient dosing habits. As practiced on the BioWell platform, dosing decisions should instead follow a conservative model guided by clinical responses and tolerability rather than speed of weight loss. The objective is to protect overall health while supporting steady progress that the body can sustain.

“An unfortunate consequence of aggressive dosing is the loss of muscle mass. It’s easier for the body to draw from muscle than it is to mobilise fat, particularly when calories and protein are low – a hallmark of aggressive dosing protocols. The nutritional and training commitment needed to offset muscle loss under more radical regimens are difficult to manage for most people. It’s far safer and more sustainable to take low doses over a longer period.”

“BioWell doctors are more measured in our approach. Conservative dosing and escalation protocols help keep muscle loss to a minimum, while structured nutrition and exercise support plans strengthen the muscular system. This also reduces the risk of nutritional deficiency and limits the physiological stress that often accompanies poorly managed treatments.”

The end goal, Dr Vosloo explains, is to safely and gradually bring South Africa’s obesity crisis under control without creating any additional harm. “Prescription-based metabolic medicine is an undeniably powerful tool in the fight against obesity – one we cannot afford to lose. It’s a lifeline for people battling weight-related illness, but it’s also become a dangerous crutch for those willing to gamble with their health just to lose a few kilograms quickly. If we want to change the health trajectory of millions, we need to rein in aggressive dosing practices and establish a common-sense structure across the sector.”

Vitamin D May Help Prevent Diabetes – Depending on Genetics

New analysis of a major clinical trial finds supplementation reduced diabetes risk in prediabetic adults with certain variations in the vitamin D receptor gene

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Prediabetes is a condition marked by higher-than-normal blood sugar levels that often leads to type 2 diabetes. A new study finds that vitamin D may help delay or prevent that progression – but only in people with certain genetic variations.

The study, published today in JAMA Network Open, found that prediabetic adults with certain variations in the vitamin D receptor gene had a 19% lower risk of developing diabetes when taking a high daily dose of vitamin D.  

The researchers analysed data from the D2d study, a large, multi-site clinical trial that tested the effect of 4,000 units of vitamin D per day versus placebo in more than 2000 US adults with prediabetes to see if a daily high dose of vitamin D would lower the chance of these particularly high-risk individuals developing diabetes.

The original trial did not find a significant reduction in diabetes risk across all participants.  

“But the D2d results raised an important question: Could vitamin D still benefit some people?” said Bess Dawson-Hughes, M75, the study’s lead author and a senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. “Diabetes has so many serious complications that develop slowly over years. If we can delay the time period that an individual will spend living with diabetes, we can stop some of those harmful side effects or lessen their severity.”

Through an earlier analysis, the D2d research team found that blood levels of 40 to 50 ng/mL of 25-hydroxyvitamin D or higher were linked to substantial and progressively larger reductions in participants’ risk of developing diabetes.  

Vitamin D circulating in the blood is converted into its active form in the body before binding to the vitamin D receptor, a protein that helps cells respond to the vitamin. The researchers wondered whether genetic differences in this receptor might explain why some people benefited from vitamin D while others did not. The pancreas’s insulin-producing cells have vitamin D receptors, suggesting the vitamin may help influence insulin release and blood sugar control.  

For the new study, Dawson-Hughes and her colleagues analysed genetic data from 2098 trial participants who had consented to DNA testing according to two groups: participants who appeared to benefit from vitamin D supplementation and those who did not. They then compared response rates by subgroups of patients sorted according to three common variations in the vitamin D receptor gene. 

This analysis revealed that adults with the AA variation of the ApaI vitamin D receptor gene (about 30% of the study population) did not respond to daily treatment with a high dose of vitamin D, compared with placebo. In contrast, the analysis found that the same treatment in adults with the AC or CC variations of the vitamin D receptor gene saw a significantly reduced risk of developing diabetes compared with those taking a placebo. 

“Our findings suggest we may eventually be able to identify which patients with prediabetes are most likely to benefit from additional vitamin D supplementation,” said Dawson-Hughes. “In principle, this could involve a single, relatively inexpensive genetic test.”

By Genevieve Rajewski

Source: Tufts University

New Report Highlights Fructose as a Key Driver of Metabolic Disease

Researchers emphasise fructose’s unique role in obesity, metabolic syndrome and other chronic diseases

Photo by Kobby Mendez on Unsplash

A new report, published in Nature Metabolism, is shedding light on the distinct and underappreciated role of fructose in driving disease, separate from its role as a simple source of calories.

Researchers examine how common dietary sweeteners, including table sugar (sucrose) and high-fructose corn syrup, impact human health. While both contain glucose and fructose, fructose has unique metabolic effects that may more directly contribute to obesity and related conditions.

“Fructose is not just another calorie,” said Richard Johnson, MD, professor at the University of Colorado Anschutz and study lead author. “It acts as a metabolic signal that promotes fat production and storage in ways that differ fundamentally from glucose.”

The report outlines how fructose metabolism bypasses key regulatory steps in the body’s energy-processing pathways. This can lead to increased fat synthesis, depletion of cellular energy (ATP) and the production of compounds linked to metabolic dysfunction. Over time, these effects may contribute to metabolic syndrome, a cluster of conditions that includes obesity, insulin resistance and cardiovascular risk.

Importantly, the authors emphasise that fructose’s impact extends beyond dietary intake alone. The body can also produce fructose internally from glucose, suggesting that its role in disease may be broader than previously recognised.

The findings come amid ongoing concern about rising rates of obesity and diabetes worldwide. Although some countries have seen declines in sugary beverage consumption, overall intake of “free sugars” remains above recommended levels in many regions and continues to increase in others.

While fructose may have once served an evolutionary purpose, helping the body store energy that can aid survival during times of food scarcity, the researchers argue that in today’s environment of constant food availability, these same mechanisms now contribute to chronic disease.

“This review highlights fructose as a central player in metabolic health,” said Johnson. “Understanding its unique biological effects is critical for developing more effective strategies to prevent and treat metabolic disease.”

By Kelsea Pieters

Source: Colorado University Anschutz

Ultra-processed Foods Linked with Greater Risk of Overweight or Obesity in Adolescents

The conclusion comes from a systematic review and meta-analysis of 23 studies and 155 000 adolescents across multiple countries and regions.

Photo by Erik Mclean

Adolescents who consume more ultra-processed foods (UPFs) have significantly higher odds of being overweight or obese, according to a new systematic review and meta-analysis published in the open-access journal PLOS One by Mekuriaw Nibret Aweke of the University of Gondar, Ethiopia, and colleagues. In the most recent of the analysed studies, higher UPF consumption was linked with more than twice the odds of overweight or obesity compared to lower UPF consumption.

Being overweight or obese during adolescence raises a person’s likelihood of developing type 2 diabetes, high cholesterol, hypertension, and metabolic syndrome. The increasing consumption of UPFs – defined as industrial products made largely from extracted, modified, or synthetic ingredients, and typically high in added sugars, salt, unhealthy fats, and chemical additives – represents one of the fastest-growing unhealthy eating patterns among young people worldwide.

In the new study, researchers systematically searched multiple databases for observational studies reporting on UPF consumption and weight outcomes in adolescents aged 10 through 19. They identified 23 eligible studies involving a total of 155 000 adolescents, conducted across 16 countries between 2008 and 2025.

In a meta-analysis of all 23 studies, the researchers found that adolescents with higher UPF consumption had 63% greater odds of overweight or obesity compared with those with lower intake (OR = 1.63; 95% CI: 1.36–1.95). The positive association was consistent across all geographic regions studied, including Africa, Asia, Europe, North America, and South America. Subgroup analysis by year of publication showed that the most recent studies, published in 2024 and 2025, reported the highest odds ratio (OR = 2.09), suggesting the association may be growing stronger as UPF consumption rises globally.

Among other aspects, the study is limited by its reliance on observational designs, which cannot establish causation, and by variation across studies in how UPF consumption and obesity were measured.

The authors conclude that public health strategies should prioritize reducing UPF consumption among adolescents through education, policy interventions, and promotion of minimally processed, nutrient-dense foods.

The authors add: “Higher consumption of ultra-processed foods is linked to a substantially increased risk of overweight and obesity among adolescents, emphasising the need for early dietary interventions.”

“Improving adolescent nutrition today is essential to protecting long-term population health and reducing healthcare costs associated with obesity-related conditions.”

Provided by PLOS

GLP-1 Medications May Also Help with Symptoms of Anxiety and Depression

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GLP-1 medications used to treat diabetes and obesity were associated with a reduced need for hospital care and sickness absence due to psychiatric reasons, a new study shows. The large register-based study was carried out in collaboration between the University of Eastern Finland, Karolinska Institutet in Stockholm and Griffith University in Australia.

Diabetes and obesity are associated with an increased risk of mental health symptoms, and similarly, individuals with mental disorders have an elevated risk of metabolic diseases such as obesity and diabetes. Researchers have long been interested in the connections between these conditions and in how pharmacological treatments may affect both metabolic and mental health disorders.

The present study, published in The Lancet Pyschiatry, included nearly 100 000 participants, over 20 000 of whom had used GLP-1 medications. Participants were followed through Swedish national registers between 2009 and 2022.

The risk of substance use was also reduced

The results showed that the use of GLP-1 medications – particularly semaglutide – was associated with a reduction in sickness absence and hospital care due to psychiatric reasons. During periods of semaglutide use, the reduction was 42% compared with periods when GLP-1 medications were not used. For depression, the risk was 44% lower, and for anxiety disorders, 38% lower. 

In addition, semaglutide use was associated with a lower risk of substance use disorders: hospital care and sickness absence related to substance use were 47% lower during periods of semaglutide use compared with periods without GLP-1 medication. The use of GLP-1 receptor agonists was also associated with a reduced risk of suicidal behaviour.

One of the study’s authors, Professor Mark Taylor from Griffith University, says such results were to be expected: “An earlier study examining Swedish registers found the use of GLP-1 medications to be associated with a reduced risk of alcohol use disorder. Alcohol-related problems often have downstream effects on mood and anxiety, so we expected the effect to be positive on these as well.”

However, the magnitude of the association surprised the researchers:
“Because this is a registry-based study, we cannot determine exactly why or how these medications affect mood symptoms, but the association was quite strong. It is possible that, in addition to factors such as reduced alcohol consumption, weight loss-related improvements in body image, or relief associated with better glycaemic control in diabetes, there may also be direct neurobiological mechanisms involved – for example, through changes in the functioning of the brain’s reward system,” says Research Director, Docent Markku Lähteenvuo from the University of Eastern Finland.

Other recent evidence on the effects of GLP-1 medications on anxiety and depressive disorders has been somewhat inconsistent, but it has been largely based on small studies.

Source: University of Finland

Could a New Type of Weight‑loss Pill Shake up the Market? Here’s What to Know About Orforglipron

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Martin Whyte, University of Surrey

A new type of daily pill has proven more effective for weight loss and blood sugar control than its currently available counterparts, according to a recent trial. The drug, known as orforglipron, could be a game-changer in the rapidly expanding oral weight-loss drug market.

The advent of the injectable weight-loss drug semaglutide (known better by its brand names Wegovy and Ozempic) marked a distinct shift in the weight-loss drugs market when it became available just a few years ago.

Semaglutide is a class of glucagon-like peptide-1 (GLP-1) medication. These drugs mimic the gut hormone GLP-1, which is released soon after eating. This hormone signals fullness to the brain, slowing digestion and stimulating the release of insulin. By replicating the action of this hormone, GLP-1 drugs have proven highly effective at managing type 2 diabetes and promoting weight loss.

Although semaglutide is widely used, a key issue with the drug is that it needs to be injected into the belly, thighs or back of the arm. This can make it difficult for patients with needle phobia or who don’t want to self-inject due to the inconvenience.

Another logistical issue with injectable GLP-1 drugs is that they require refrigeration throughout the supply chain. This can pose a challenge in low- and middle-income countries.

It’s for these reasons that researchers and developers have started investigating the efficacy of oral versions of semaglutide.

Based on current research, it appears that oral semaglutide is very effective. However, it must be taken on an empty stomach – and users must wait 30 minutes before eating or drinking.

Alongside being expensive to produce, it also has poor bioavailability compared with injectable semaglutide. This means only about 1% of the ingested drug is absorbed and able to exert its effects.

But a recent phase 3 clinical trial has shown that a new type of oral weight-loss pill may have overcome these issues – proving to be more effective than the current oral semaglutide products on the market.

Oral weight-loss pill

The recent 52-week phase 3 trial involved 1,698 adults with type 2 diabetes across six countries. It set out to compare current oral semaglutide products against orforglipron, which is also taken as a daily tablet.

The primary measure researchers were looking for was a reduction in HbA1c. This blood test reflecting average blood sugar levels over three months is the standard indicator of diabetes control. Diabetes is present if HbA1c is 6.5% or more.

From a baseline average HbA1c of 8.3%, it was found that after 52 weeks, orforglipron was able to reduce this value by an average of 1.71–1.91%. In comparison, oral semaglutide only reduced HbA1c by 1.47%.

Not only did orforglipron meet the trial’s goals of proving it was as effective to oral semaglutide, it proved it was superior for lowering blood sugar. The participants who took orforglipron also lost more weight – an average of 6.1kg-8.2kg, compared with 5.3kg in those taking semaglutide.

However, a key issue highlighted by the trial was one of tolerability.

GLP-1 drugs can cause gastrointestinal side-effects such as nausea, vomiting, diarrhoea and constipation. In this latest trial, around 59% of participants on orforglipron reported such symptoms, compared with 37–45% on semaglutide.

The reason for this difference may be the more prominent, daily peak drug concentrations with orforglipron. The consequence was that around 10% of orforglipron participants discontinued treatment due to adverse effects. Just 4-5% of those taking semaglutide discontinued treatment.

Future studies may want to look at how orforglipron compares with injectable semaglutide. Photo by Haberdoedas on Unsplash

No head-to-head trials have been done of injectable GLP-1 versus orforglipron. However, the weight loss seen in this study of people with type 2 diabetes is broadly comparable with that previously observed with injectable GLP-1.

Market implications

The trial’s results show that orforglipron, which was developed by Eli Lilly, can be considered one of semaglutide’s most credible challengers.

Another remarkable thing about orforglipron is that it belongs to a new category of drugs called small-molecule drugs. This means it’s a synthetic chemical compound small enough to be absorbed directly through the gut wall. There, it’s able to act on GLP-1 receptors, even though it isn’t of a similar structure to a GLP-1 hormone.

Oral semaglutide, on the other hand, is a peptide drug. This means the structure of its amino acids (one of the building blocks of protein) closely resembles that of the natural GLP-1 hormone.

As a small-molecule drug, orforglipron is cheaper and simpler to manufacture than peptide-based drugs such as semaglutide.

And as with oral semaglutide, it requires no refrigeration. This gives it a logistical advantage over injectable GLP-1 formulations – a potentially important consideration for expanding access in low- and middle-income countries, where cold chain infrastructure is unreliable.

It remains to be seen, however, how orforglipron will perform against oral semaglutide in the broader market.

Although this latest trial has shown it is superior for controlling blood sugar and aiding weight loss, its higher rate of side-effects and treatment discontinuation may temper enthusiasm. In a crowded and competitive market, long-term adherence – shaped as much by tolerability as by efficacy – is probably a critical differentiator.

Orforglipron is still undergoing trials in patients with obesity but without diabetes.

Martin Whyte, Associate Professor of Metabolic Medicine, University of Surrey

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Study Finds Low Response Rate by Clinicians to Elevated Levels of Lp(a)

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Elevated Lipoprotein(a) [Lp(a)] is an independent, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD), with levels >50mg/dL affecting 20–30% of the global population. Despite therapeutic limitations, interest in Lp(a) has increased, driven by its prognostic value and the emergence of targeted therapies. However, with increasing guideline-directed Lp(a) testing, clinician response to elevated concentrations, especially in the absence of guideline-based treatment indications, remains unclear.

In a new study and presentation at the American College of Cardiology, researchers found that elevated Lp(a) was associated with earlier and more frequent initiation of preventive pharmacotherapy.  These response rates were modest in a low-risk, primary prevention study population.

Specifically, nearly 80% of patients with elevated Lp(a) > 50mg/dL did not initiate lipid-lowering therapy in the absence of other ASCVD risk factors. Drugs that drastically lower “bad” LDL cholesterol (PCSK9 inhibitors) and aspirin initiation was even less common, suggesting selective rather than systematic responses to elevated Lp(a). Together, these findings suggest that elevated Lp(a) appears to only occasionally influence prescribing behaviour – behaviour consistent with previous reports.

“While not currently a standard indication for statin therapy alone, elevated Lp(a) is increasingly used by clinicians as a “risk enhancer” to guide more aggressive, albeit often unstandardised, preventive measures,” says corresponding author Sheilah A. Bernard MD, associate professor of medicine at Boston University Chobanian & Avedisian School of Medicine.

The researchers conducted a multicentre retrospective observational cohort study evaluating initiation of preventive pharmacotherapy following Lp(a) measurement among nearly 15 000 patients at low risk for ASCVD. Within 90 days of Lp(a) measurement, lipid-lowering therapy initiation was uncommon but more frequent among patients with elevated Lp(a) compared to those with non-elevated Lp(a). PCSK9 inhibitor initiation was rare but more frequent among patients with elevated Lp(a). Similarly, aspirin initiation was uncommon but more frequent among patients with elevated Lp(a).

According to the researchers, these findings should not be interpreted as indicating that such prescribing is guideline-directed. “Current recommendations recognise Lp(a) as a risk-enhancing factor rather than as a treatment target, and no therapy is approved solely for Lp(a) elevation. Our analysis describes contemporary practice rather than appropriate management,” adds Bernard who also is a cardiologist at Boston Medical Center.

The findings also appear online in the American Journal of Preventive Cardiology.

Source: EurekAlert!

How do GLP-1 Agonists Improve Pancreatic Beta Cell Health?

Salk Institute researchers find protein that connects GLP-1 agonist drugs to long-term, broad genomic responses that can promote pancreatic health and resilience

Small (left) and large (right) condensates of the Mediator complex inside nuclei of a pancreatic beta cell-derived cell line. Salk researchers discovered that GLP-1s interact with the multi-protein complex called Mediator to cause a broad genomic response.
Click here for a high-resolution image.
Credit: Salk Institute

GLP-1s are building a reputation as “wonder drugs.” First characterised for their ability to improve insulin release and treat diabetes, the drugs were later found to promote weight loss and improve cardiovascular health. In addition to these surprising bonus benefits is the ability of GLP-1 drugs to improve pancreatic beta cell health. But how, exactly, are they doing that?

Salk Institute researchers are burrowing down into the mechanistic details behind how GLP-1 drugs promote viability and stress resistance in pancreatic beta cells. Since cellular performance adaptations arise from gene expression changes, the team screened for regulatory proteins that can flip “on” advantageous gene programs during prolonged GLP-1 use. They identified a protein called Med14, part of a larger protein complex called Mediator, that was enabling the GLP-1-dependent changes in gene expression that lead to pancreatic health benefits.

The study was published in Proceedings of the National Academy of Sciences on March 4, 2026, and was funded by federal research grants from the National Institutes of Health and private philanthropy.

“The broad salutary effects of GLP-1 drugs in diabetes, cardiovascular disease, and obesity have sparked a wave of exciting scientific research at the mechanistic level. We’re left wondering,  ‘How are GLP-1s causing these effects?’” asks senior author Marc Montminy, MD, PhD, a biochemist, physiologist, and distinguished professor emeritus at Salk. “We were able to single out a protein, Med14, whose activation downstream of GLP-1 helps reprogram pancreatic beta cell gene expression to improve the cells’ viability and insulin production.”

What are GLP-1 drugs?

Often simply called “GLP-1 drugs” or “GLPs,” glucagon-like peptide-1 receptor agonists work by mimicking a hormone our bodies naturally make. The hormone, called glucagon-like peptide-1, helps regulate blood sugar.by promoting the secretion of insulin. They do so by attaching to corresponding GLP-1 receptors on pancreatic beta cells, which then produce and release insulin into the body.

But GLP-1 drugs differ in one significant way from their natural counterpart: Unlike human-made GLP-1 hormones that appear and disappear quickly around mealtimes, artificial GLP-1 receptor agonists can stick around much longer. The Salk researchers suspect this longer-term presence may explain some of the “wonder drug” benefits of GLP-1 drugs. But what, exactly, on the molecular level, are GLP-1 drugs doing when they stick around? And how does their staying power turn into effects like lower risk of stroke or improved osteoarthritis?

“The fact that these drugs based off our hormones are stable seems to be important to the longer-term effects we’re witnessing in pancreatic beta cells and other tissues,” says first author Sam Van de Velde, PhD, a staff scientist in Montminy’s lab. “To understand how we are getting these longer-term effects, we need to study these drugs on a longer time scale – and that’s exactly what we did.”

How do GLP-1 drugs influence pancreatic health?

When the hormone GLP-1 finds a pancreatic beta cell, the ensuing chain of signals, proteins, and gene expression changes that lead to insulin secretion is very well documented. On the other hand, the mechanisms and changes on the longer-term GLP-1 drug scale are poorly understood.

So, the researchers set out on a molecular fishing expedition in a pancreatic beta cell line. The team was hoping to hook a protein (or proteins) that, post-GLP-1 activation, had a particular chemical modification called phosphorylation. And that’s exactly what they found in Med14.

Med14 is a subunit in a multi-protein complex called Mediator, which is a well-described general regulator of gene expression throughout the genome. To confirm whether Med14 was an integral link between GLP-1 drugs and ultimate changes in gene expression and pancreatic beta cell behavior, the researchers decided to mutate Med14, making the protein resistant to phosphorylation.

The gene expression patterns associated with prolonged GLP-1 drug exposure disappeared in a Med14 mutant pancreatic beta cell line and in beta cells of a Med14 mutant mouse model. With working Med14, the helpful gene programs were activated – supercharging pancreatic beta cells to grow and better handle sugar-rich environments after meals.

How else might GLP-1 drugs affect the body?

None of the Salk team’s experiments were conducted in humans, yet the relevance remains. For example, some of the genes regulated by Med14 phosphorylation are known to be linked to type 2 diabetes susceptibility in humans.

“Our findings unexpectedly reveal that phosphorylation of just a small part of the Med14 protein plays a significant role in the response to GLP-1 drugs – and in the metabolic response to hormones more broadly,” says Reuben Shaw, PhD, a professor and holder of the William R. Brody Chair at Salk, and director of the National Cancer Institute-Designated Salk Cancer Center. “Now there are many new questions to answer, from validating our findings in human tissues to seeing whether Med14 has a similar role in other cells and organs.”

The team is especially curious about the effects of prolonged GLP-1 exposure beyond pancreatic beta cells. One of the messenger molecules between GLP-1 and Med14, called cAMP, is a commonly used messenger molecule in many other situations that don’t include GLP-1. With that in mind, could other drugs or hormones activate genetic programs similar to GLP-1? And what’s going on in other metabolically intensive tissues, like fat?

The questions keep coming for the so-called “wonder drug,” and Salk scientists are enthusiastically working to answer them.

Source: Salk Institute

Can GLP-1 Agonists ‘Change the Weather’ for Osteoarthritis?

Photo by Towfiqu barbhuiya

For GPs, solutions for treating osteoarthritis are frustratingly limited – it’s like the weather, everyone talks about it but nobody does anything about it. While standard care can relieve symptoms, there is currently no way to regenerate the actual lost cartilage in the joints. Some experimental treatments have proven successful in animal models and in petri dishes, but those are still many years away from being approved and available on the market.

But what if there was a currently available drug that could be repurposed? Since overweight and obesity worsen osteoarthritis symptoms by placing excess strain on weight-bearing joints, GLP-1 agonists such as semaglutide have proven that they can help by promoting rapid weight loss, as demonstrated by the STEP-9 trial.

Research into GLP-1s has now revealed that they may offer a whole constellation of other benefits, such as a potential reduction in stroke risk. Now, it appears that GLP-1 agonists may have a direct effect on osteoarthritis independent of weight loss. In our podcast, we look at a recently published article in Cell Metabolism that suggests that GLP-1 agonists might go beyond just the weight loss – promote actual cartilage regrowth by jumpstarting the joint cells’ energy processing pathways. We also explore some of the caveats of potentially using GLP-1 agonists in this way, such as a lack of understanding of the long term effects, as well as the well-documented occurrence of muscle loss.

Specific Brain Signals Rapidly Eliminate Body Fat in Mice

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Researchers at WashU Medicine have identified a potent pathway that begins in the brain and leads to loss of all body fat without reducing food intake. The study is reported in Nature Metabolism.

The team – led by senior author Erica L. Scheller, DDS, PhD, an associate professor in the Division of Bone and Mineral Diseases in the Department of Medicine; Xiao Zhang, PhD, a former graduate student in Scheller’s lab who is now a postdoctoral fellow at the University of Pennsylvania School of Medicine; and Sree Panicker, a graduate student in Scheller’s lab – was inspired by a unique population of fat cells located deep within the skeleton.

“About 70% of our bone marrow is filled with fat that doesn’t respond to diet or exercise,” said senior author Scheller. “We wanted to figure out why.”

The team found that these special cells, called constitutive bone marrow adipocytes, expressed high levels of proteins that inhibit fat breakdown. This causes resistance to fat loss in day-to-day settings. “We call these cells stable adipocytes,” said Zhang, the study’s first author. In mice, sustained injection of leptin, a hormone, into the brain was able to unlock the stable adipocytes by putting the body into a state of low glucose and insulin. This reduced the inhibitors of fat breakdown, causing complete loss of body fat within days, even though the mice were still eating normally.

This pathway is so powerful that the scientists caution against using it in humans until it is better understood. Stable adipocytes occur in places like the bone marrow, in the hands and feet, and around important glands. In severe wasting disorders, loss of fat within these cells is associated with bone fractures and reduced quality of life. Scheller’s team hopes to prevent this loss and preserve health in patients with severe wasting disorders by defining the mechanisms of stable fat loss. Conversely, methods to activate fat loss from stubborn adipocytes may support future treatments for obesity. This work was funded by the National Institutes of Health (NIH).

By Jaci McDonald

Source: Washington University