Weight Loss

Posted on Exercise, Obesity, Weight Loss

Study finds intense exercise may suppress appetite in healthy humans

What is moderate and vigorous exercise?

A rigorous workout suppresses hunger more than moderate exercise in healthy adults, with females potentially more affected, according to a small study published in the Journal of the Endocrine Society.

The study investigates how exercise intensity affects ghrelin levels and appetite in men and women. Ghrelin, known as the “hunger hormone,” is linked to feelings of hunger.

“We discovered that high-intensity exercise reduces ghrelin levels more effectively than moderate-intensity exercise,” said lead author Kara Anderson, Ph.D., from the University of Virginia and the University of Virginia Health System in Charlottesville, Virginia. “Additionally, we found that individuals felt ‘less hungry’ after high-intensity exercise compared to when they engaged in moderate-intensity exercise.”

Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. The study noted that data on the impact of exercise intensity on AG and DAG levels and their effects on appetite is sparse and primarily limited to males.

To address this shortfall, the study examined eight males and six females. Participants fasted overnight and then completed exercises of varying intensity levels, determined by blood lactate measurements, followed by self-reported measurements of appetite.

The study noted that females had higher levels of total ghrelin at baseline compared with males. However, only females demonstrated “significantly reduced AG” following the intense exercise.

“We found that moderate intensity either did not change ghrelin levels or led to a net increase,” the study noted. These findings suggest that exercise above the lactate threshold “may be necessary to elicit a suppression in ghrelin.”

Researchers also acknowledged that more work is needed to determine the extent to which exercise’s effects differ by sex.

Ghrelin has been shown to have wide-ranging biological effects in areas including energy balance, appetite, glucose homeostasis, immune function, sleep, and memory.

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” Anderson said. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

Posted on Diabetes, Obesity, Weight Loss

Weight loss could reduce the risk of severe infections in diabetics

Small study finds 6 point stimulation of outer ear with simple metal beads helped reduce waist circumference, body fat and BMI in men living with obesity

New research being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain (9-13 September) suggests that weight loss interventions could reduce the risk of severe cases of flu and other infections in people with diabetes.

The study by Rhian Hopkins and Ethan de Villiers at the University of Exeter Medical School in Exeter, UK, found evidence suggesting that a higher BMI is associated with severe infections.

In contrast, there was no evidence that mild hyperglycemia contributes to the likelihood of a severe infection.

Hopkins stated, “Up to one in three hospitalizations among people with diabetes are due to infections, and individuals with diabetes are twice as likely to be hospitalized with infections compared to the general population. They also face a high risk of readmission.”

Previous studies have found that higher BMI and poor blood sugar control are associated with severe infections. However, these studies have been observational and thus haven’t been able to prove causal links.

“If one or both of these factors can be shown to be causal, it may be possible to design interventions to lower the risk of severe infections in those at high risk, such as people with diabetes.”

The recent study utilized data from the UK Biobank, which contains medical and genetic information on approximately 500,000 individuals in the UK. The study aimed to investigate the impact of elevated BMI and inadequate blood sugar regulation on the likelihood of being hospitalized due to bacterial and viral infections.

A higher BMI was found to be associated with hospitalisation with infections.  Similarly, every five-point increase in BMI was associated with a 32% increase in the likelihood a severe viral infection.

An association between mild hyperglycemia and severe infections was found. The likelihood of hospitalization due to bacterial infection increased by 32% per 10mmol/mol rise in HbA1c, a measure of blood sugar levels.

This suggested that a higher BMI is one of the causes of severe bacterial and viral infections.

However, mild hyperglycaemia did not appear to cause severe infections.

Although the study didn’t focus on individuals with diabetes, Ms Hopkins says that, given their vulnerability to infections, the results may be particularly relevant to them.

She adds: “Infections are a significant cause of death and ill health, particularly in people with diabetes. Anyone admitted to hospital with a severe infection is also at high risk of being admitted again with another. However, we currently have few practical ways to prevent this.

“This study demonstrates that higher BMI is a cause of hospital admission with infection. Clinicians could discuss weight loss options for people with a high BMI at risk of severe infections and readmission to hospital for infection.”

“While this message may be particularly relevant to people with diabetes, it applies more widely.”

Further research is needed to determine if more severe hyperglycaemia is a cause of severe infections.

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, 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, Weight Loss

Young people are increasingly using Wegovy and Ozempic.

Public interest in weight loss drugs like Wegovy and Ozempic is surging, but national data on dispensing patterns in the United States are surprisingly scarce. 

Now, a national study from Michigan Medicine shows that the use of these weight loss drugs is increasing rapidly in adolescents and young adults 12-25 years, especially females. 

Using 2020 – 2023 data from a national database representing 92% of pharmacies, the study team found a 594% increase in the monthly number of adolescents and young adults using Wegovy, Ozempic, and other glucagon-like peptide-1 receptor agonists (GLP-1RAs). 

For females, this increase was even more pronounced. 

The number of female adolescents 12-17 years using GLP-1RAs increased by 588%, compared with 504% for male adolescents. 

The number of female young adults 18-25 years using GLP-1 RAs increased by 659%, compared with 481% for male young adults. 

“This is the first study to document national trends in GLP-1RA dispensing in any population, including youth, ” said Joyce Lee, MD, MPH, the paper’s lead author. Lee is a pediatric endocrinologist and Professor of Pediatrics in the Susan B. Meister Child Health Evaluation and Research Center at the University of Michigan Medical School, the C.S. Mott Children’s Hospital, and the Caswell Diabetes Institute. 

GLP-1RAs were approved for type 2 diabetes in 2005 and for weight management in 2014. 

Interest in these drugs surged in 2021 when semaglutide was approved for weight management in adults under the brand name Wegovy and increased even further when Wegovy was approved for weight management in adolescents at the end of 2022. 

The report finds that endocrinologists, family medicine physicians and nurse practitioners were among the top prescribers of GLP-1 RAs to youth, suggesting that these clinicians should be the focus of efforts to ensure safe and appropriate prescribing. 

For example, because the biggest usage increase occurred in females, clinicians need to educate female patients about the potential safety risks of these GLP-1 RAs during pregnancy. 

The report also found that Ozempic dispensing increased in youth, even though It is not approved for children for type 2 diabetes or weight management. 

“This finding suggests increasing off-label use of Ozempic for weight management in adolescents and young adults,” said Kao-Ping Chua, MD, the paper’s senior author and a CHEAR Centre member.

Lee adds that some concerns have been raised about both the cost of GLP-1 RAs, which are expensive and meant to be taken over the longterm, as well as the unknown effects of these drugs on growth and development in youth. 

“The increasing use of GLP-1 RAs highlights the importance of understanding the long-term safety, efficacy, and cost-effectiveness of GLP-1RAs in adolescents and young adults,” she said.