Obesity

Posted on Obesity, Weight Loss

Weight loss of up to 13% in 3 months with 1-a-day tablet

“Amycretin mimics the action of two peptide hormones in one single molecule.”

Amycretin functions as both an amylin and glucagon-like peptide-1 (GLP-1) receptor agonist. Both of these hormones play a key role in regulating appetite and the feeling of hunger and have been shown to contribute to weight loss.

GLP-1 based treatment options are currently administered via injections. Amylin-based treatments undergoing clinical development also use this delivery method. There are no tablet-form treatment options targeting both of these biologies.

In a single-centre, placebo-controlled, double-blinded phase 1 study, adult participants with a BMI of 25.0-39.9 kg/m2 without diabetes were randomized to receive amycretin or a placebo once a day for up to 12 weeks.

The research, conducted by Novo Nordisk A/S and a clinical research unit in the US, consisted of two parts: single- and multiple-ascending dose studies. In the single-ascending dose part, doses of amycretin were tested orally, starting at 1 mg per day and increasing to 25 mg. The 10-day multiple-ascending doses study investigated doses ranging from 3 to 12 mg, while the 12-week multiple-ascending doses study involved step-wise dose escalation, starting at 3 mg and reaching a final dose of 2×50 mg.

In the first-in-human trial, amycretin appeared to have a safe and tolerable profile consistent with the drug receptor classes. Side effects were mainly mild to moderate in severity and of gastrointestinal nature, including nausea and vomiting.

Sure, the following shows the revised text: “After the trial, it was found that participants who took amycretin experienced greater weight loss compared to those who took the placebo. Those taking 50 mg of amycretin lost an average of 10.4% of their body weight after 12 weeks of treatment, while those who took the maximum tested dose of 2x50mg experienced a 13.1% reduction in body weight. In contrast, those taking the placebo only lost an average of 1.1% of their body weight during the same period.”

Notably, at the end of the treatment period, weight loss had not reached a plateau for participants taking amycretin, indicating the potential for further weight loss with extended use.

The study’s authors conclude that daily oral amylin treatment in adults with overweight or obesity and without diabetes demonstrated a safe and tolerable profile, aligning with the drug receptor classes, and resulted in significant reductions in body weight.

“A single molecule that targets both amylin and GLP-1 biology in a tablet form could provide a more convenient approach to improving outcomes for individuals with overweight or obesity.”

“However, larger and longer studies are necessary to fully evaluate the drug’s safety profile and potential.”

Posted on Diabetes, Obesity

Over a decade, there was an almost 20% increase in the prevalence of type 2 diabetes.

Age, race, income level, obesity, physical inactivity all factor in risk of diabetes diagnosis
The risk of being diagnosed with diabetes is influenced by factors such as age, race, income level, obesity, and physical inactivity.

Type 2 diabetes increased by nearly 20% from 2012 to 2022, as per a recent study from the University of Georgia.

The researchers discovered an increase in diabetes across all sociodemographic groups. However, non-Hispanic Black individuals were particularly affected by the disease, with just under 16% of Black study participants reporting a diagnosis of Type 2 diabetes.

“More than one in five individuals aged 65 or older had the condition. In the same age group, the likelihood of being diagnosed with diabetes was more than 10 times higher than for people in the 18-to-24-year age bracket. Those between the ages of 45 and 64 were over five times more likely to receive the diagnosis.”

The research also revealed that individuals with lower incomes had a notably higher prevalence of diabetes compared to those with higher incomes. People with higher incomes had a 41% lower likelihood of being diagnosed with the disease, while individuals with a college education were 24% less likely to receive a diabetes diagnosis.

“Diabetes is on the rise in the U.S. and is projected to continue increasing in the future,” stated Sulakshan Neupane, the lead author of the study and a doctoral student in UGA’s College of Agricultural and Environmental Sciences. “The annual cost of diabetes is approximately $412 billion, encompassing medical expenses and indirect costs such as loss of productivity. This substantial amount is expected to grow as more individuals are diagnosed with the disease.”

South, Midwest particularly vulnerable to diabetes

The researchers utilized data from the nationally representative Behavioral Risk Factor Surveillance System, an ongoing health survey of over 400,000 individuals.

They used the same dataset for a paper that was published by the American Journal of Preventive Medicine in April. The paper highlighted the economic impact of Type 2 diabetes and the increased prevalence of the condition over the same study period as the current paper.

The researchers found regional differences in diabetes prevalence, with the South and Midwest experiencing large increases in Type 2 diabetes cases. Arkansas, Kentucky, and Nebraska reported the highest increases between 2012 and 2022. Over the decade-long study period, ten states saw increases of 25% or more: Arkansas, Kentucky, Nebraska, Texas, Alabama, Minnesota, Illinois, West Virginia, Delaware, and Massachusetts. “In these areas, people are at a higher risk of developing diabetes, so policymakers and public health officials need to focus on these regions,” Neupane said.

Overweight, obese individuals more likely to have diabetes

Obese and overweight individuals had a higher likelihood of being diagnosed with Type 2 diabetes. In 2022, 1 in 5 obese individuals reported having the disease, while 1 in 10 overweight participants reported the condition.

Physically active individuals had a prevalence of under 10% for diabetes, while inactive people experienced a rate closer to 19%.

“It is crucial to identify these risk factors and take steps to mitigate them,” Neupane emphasized. “Being more physically active and paying greater attention to your physical health is essential. While certain risk factors such as age and race are beyond our control, some measures can be taken to reduce the risk of diabetes, such as adopting a healthy diet, maintaining an active lifestyle, and managing weight.”

Posted on Diabetes, Obesity, Weight Loss

The potential to enhance the effectiveness of commonly used weight-loss medications.

Weight loss
Weight loss

According to new research from the University of Michigan, a network of proteins found in the central nervous system could be harnessed to increase the effectiveness and reduce the side effects of popular diabetes and weight-loss drugs. 

The study, appearing today in the Journal of Clinical Investigation, focused on two proteins called melanocortin three and melanocortin 4, found primarily on the surface of neurons in the brain. These proteins play a central role in regulating feeding behaviour and maintaining the body’s energy balance.

Melanocortin 3 and melanocortin 4 impact everything from sensing long-term energy stores to processing signals from the gut regarding short-term fullness or satiety, said U-M physiologist Roger Cone, who led the study.

The class of drugs known as GLP-1 agonists, which includes semaglutides (e.g., Ozempic) and tripeptides (e.g., Mounjaro), has received substantial attention recently for their effectiveness in treating not only type 2 diabetes but also obesity, heart disease, and potentially addiction. They work by mimicking a natural hormone that the gut produces when it is full, triggering the brain to reduce feeding behavior.

“So the obvious question for us was: How do these GLP-1 drugs, which work by manipulating satiety signals, function when we prime the melanocortin system?” said Cone, professor of molecular and integrative physiology at the U-M Medical School and director of the U-M Life Sciences Institute where his lab is located.

Working in mouse models, Cone and his colleagues tested the effects of several hormones that reduce food intake. They compared the results in normal mice with mice that genetically lacked the MC3R protein, in mice that were given chemicals to block the activity of MC3R, and in mice that were given a drug to increase the activity of MC4R. (Because MC3R is a natural negative regulator of MC4R, meaning it decreases the activity of MC4R, blocking MC3R and increasing MC4R activity has similar effects.)

In all cases, Naima Dahir, the study’s first author and a postdoctoral research fellow in Cone’s lab, and colleagues found that adjusting the melanocortin system—either by inhibiting MC3R or increasing MC4R activity—made the mice more sensitive to GLP-1 drugs and other hormones that affect feeding behavior. The mice that were given a GLP-1 drug in combination with an MC4R agonist or MC3R antagonist showed up to five times more weight loss and reduced feeding than mice receiving only the GLP-1 drugs.

“We found that activating the central melanocortin system hypersensitizes animals to the effects of not just GLP-1s, but to every anti-feeding hormone we tested,” Cone said.

The researchers also measured activity in parts of the brain thought to trigger nausea in response to GLP-1 drugs and observed no increased activation when GLP-1 drugs were combined with alterations to the melanocortin system. In contrast, priming of the melanocortin neurons significantly increased GLP-1 drug activation of neurons in hypothalamic feeding centers in the brain.

The findings indicate that pairing the existing GLP-1 drugs with an MC4R agonist could increase sensitivity to the desired effects of the drugs by up to fivefold, without increasing unwanted side effects. Ultimately, this approach could enable patients who are sensitive to the side effects to take a lower dose, or could improve the results in patients who have not responded to the existing drug dosages. Further drug development and clinical testing are needed before this can occur.

While this research has been conducted only in mouse models, Cone is optimistic that the results will translate well to humans.

“The melanocortin system is highly conserved in humans,” he said. “Everything we’ve observed in the mouse over the past decades studying these proteins has also been found in humans, so I suspect that these results would also be translatable to patients.”

Posted on Diabetes, Exercise, Obesity

In the evening, physical activity improves glucose regulation in overweight and obese adults.

adult with obesity practicing running

Adults with obesity practising running CREDIT University Of Granada

The results, obtained by a team of scientists from the University of Granada (UGR), could have multiple practical implications, especially for people at risk of developing insulin resistance or type 2 diabetes.

The UGR’s PROFITH CTS-977 Research Group, in collaboration with the “San Cecilio” and “Virgen de las Nieves” University Hospitals in Granada; the Public University of Navarre; the Centre for Networked Biomedical Research on Physiopathology of Obesity and Nutrition (CIBEROBN); and the Centre for Networked Biomedical Research on Frailty and Healthy Ageing (CIBERFES), has studied the effect of accumulating moderate-to-vigorous physical activity on glucose levels in overweight and obese adults.

Physical activity is known to positively affect glucose regulation, but does it matter what time of day we do it? It was previously unknown whether being more active at a particular time of day (morning, afternoon or evening) could maximise the cardiometabolic benefits of physical activity. “Choosing the ideal time of day seems to be an emerging strategy to enhance the benefits of physical activity on glucose metabolism, especially for those with insulin resistance or at risk of developing type 2 diabetes,” the researchers note.

The study results show that accumulating more moderate-to-vigorous physical activity in the evening, i.e. between 18:00 and 00:00, appears to have a positive effect on glucose regulation in men and women who are overweight or obese. In addition, the benefits of physical activity are greater in people with some form of impaired glucose metabolism, such as elevated glucose levels, glycated haemoglobin and/or fasting insulin resistance index. The results were similar for both men and women.

A total of 186 overweight or obese adults (50% of whom were women) with an average age of 47 years took part in the study. These participants wore an accelerometer and a continuous glucose monitor for 14 days to measure their physical activity and glucose levels 24 hours a day. Days were classified as “inactive” if no physical activity was recorded; as “morning”, “afternoon”, or “evening” if more than 50% of the recorded minutes of physical activity for that day were registered between 6:00-12:00, 12:00-18:00 or 18:00-00:00, respectively; or as “mixed” if none of these defined time periods accounted for more than 50% of the physical activity for that day.

The results could have several practical implications, especially for those at risk of developing insulin resistance or type 2 diabetes, and highlight the importance of considering the time of day when prescribing physical activity. This information may be crucial in improving the effectiveness of exercise interventions in these groups.

Posted on Diabetes, Obesity

A new study shows the long-term effectiveness of gastric bypass in treating type 2 diabetes and obesity.

Diabetes in remission for 15 years, weight loss maintained for 20 years in large study
In a large study, diabetes was in remission for 15 years, and weight loss was maintained for 20 years.
Roux-en-Y gastric bypass, a type of weight-loss surgery, kept type 2 diabetes in remission for up to 15 years and most of the weight off for up to 20 years in one of the largest long-term studies of patients undergoing the procedure. The study* was presented today at the American Society for Metabolic and Bariatric Surgery (ASMBS) 2024 Annual Scientific Meeting.

Researchers from Geisinger Medical Center in Danville, PA, analyzed diabetes remission rates and weight-loss outcomes of 2,045 patients who had a gastric bypass at their centre between 2001 and 2008 and followed them for up to 20 years. Before surgery, patients, on average, were 46 years old with a body mass index (BMI) of 47.9.

Of the 677 patients with pre-operative diabetes, remission rates were 54% at the three-year mark but dropped to 38% after 15 years. Only about 10% of patients with insulin-dependent diabetes had remission in the same timeframe, and the rate of persistent diabetes was higher in patients who had insulin-treated diabetes before surgery. 
After 18 months, peak weight loss of 31.8% was achieved, stabilizing at 23% after 10 years and up to the 20-year mark. The overall 15-year mortality rate was 13.3%, which was 37.4% among patients with diabetes and older than 60. No deaths were related to the surgical procedure itself.
“With the availability of medical and endoscopic therapies, the demonstration of the long-term effectiveness of gastric bypass that exceeds that of these alternatives is critical to providing the right intervention for the right patient at the right time,” said study author Anthony T. Petrick, MD, FACS, Director, Division of Bariatric and Foregut Surgery, Geisinger Health System.
The ASMBS reports that nearly 280,000 metabolic and bariatric procedures were performed in 2022, representing only about 1% of those who meet eligibility requirements based on BMI.
“The study is an important contribution to the current understanding of long-term outcomes of gastric bypass because of the extremely high follow-up rates,” said Marina Kurian, MD, ASMBS President, who was not involved in the study.
According to the U.S. Centers for Disease Control and Prevention (CDC), obesity affects 42.4% of Americans. Studies show the disease can weaken or impair the body’s immune system and cause chronic inflammation, and increase the risk of many other diseases and conditions including cardiovascular disease, stroke, type 2 diabetes, and certain cancers. 
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