PDA Autism Explained: A Look at ‘Pathological Demand Avoidance’
Abdominal fat linked to chronic pain, especially in women
Reducing excess fat deposits in the abdomen may help reduce chronic musculoskeletal pain, especially if it’s experienced at multiple body sites, suggest the researchers. Previously published research has shown that obesity is associated with musculoskeletal pain. Still, it’s not known if excess fat tissue is linked to chronic musculoskeletal pain at multiple body sites, say the researchers. To find out, they drew on data from 32,409 participants in the UK Biobank study who completed questionnaires and underwent health assessments. Around half (51%) were women, and their average age was 55.
They underwent MRI scans of their abdomen to measure the amount of fat around the abdominal organs (visceral adipose tissue or VAT) and the amount of fat just under the skin that can be pinched (subcutaneous adipose tissue or SAT). When attending for their scan, participants were asked if they had experienced any pain in their neck/shoulder, back, hip, knee or ’all over the body’ for more than 3 months. The MRI scan and pain assessments were repeated around 2 years later for 638 participants. Comprehensive analyses showed a dose-response association between the number of chronic pain sites and VAT, SAT, the ratio of the two, and weight (BMI). The association was stronger in women, among whom the odds ratio of a higher number of chronic pain sites was twice as high for VAT and 60% greater for both SAT and the VAT: SAT ratio. In men, these odds ratios were 34% 39%, and 13% higher, respectively.
Higher levels of fat tissue were also associated with greater odds of reporting chronic pain, and again the association was more pronounced in women. All these associations remained even after adjusting for age, height, ethnicity, household income, educational attainment, alcohol intake, smoking status, physical activity, coexisting conditions, sleep duration, psychological problems and length of follow-up.
This is an observational study, and as such, can’t establish cause and effect, and the authors also acknowledge various limitations. These include the relatively small size of the repeat imaging sample and the absence of an assessment of severity in the pain questionnaire. They add that more follow-up visits would also have allowed more information to be gathered on patterns and fluctuations in the number of chronic pain sites. However, they conclude: “Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain. Therefore, reducing abdominal adiposity may be considered a target for chronic pain management, particularly in those with pain in multiple sites and widespread pain.” They suggest that the stronger associations seen in women may be a consequence of sex differences in fat distribution and hormones.
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.”
Semaglutide hydrogel could reduce diabetes shots to once a month
French researchers have created a new drug delivery system, which, according to recent research, could reduce the dosing frequency of semaglutide, a drug used for type 2 diabetes and weight control, to just once a month. This research will be presented at this year’s annual meeting of The European Association for the Study of Diabetes (EASD) in Madrid (9-13 Sept).
“GLP-1 drugs have revolutionized type 2 diabetes care. However, the need for weekly injections can be burdensome for patients. A once-a-month injection could significantly improve the treatment experience for people with diabetes or obesity, making it easier to stick to their medication regimens. This could lead to an improved quality of life, reduced side effects, and fewer diabetes-related complications,” stated Dr. Claire Mégret, the lead author from ADOCIA, a biotechnology company based in Lyon, France, that developed the hydrogel.
Semaglutide functions by imitating the hormone glucagon-like peptide 1 (GLP-1). It is currently authorized for treating type 2 diabetes patients with insufficient glycemic control and long-term weight management.
Clinical studies indicate that adherence to injected semaglutide is between 39% and 67% for type 2 diabetes patients at one year [1a], and 40% for patients using the drug for weight loss [1b]. Similarly, adherence to daily oral pill formulations is approximately 40% at one year [2].
Long-acting delivery formulations could enhance drug effectiveness and safety by maintaining consistent drug levels in the body at optimal concentrations.
The new hydrogel delivery platform utilizes two innovative degradable polymers that are chemically linked to each other to create a gel. This gel enables a slow, sustained release of soluble peptides over a period of 1 to 3 months.
“A small amount of gel, called a ‘depot,’ containing semaglutide is injected under the skin,” explained Dr. Mégret. “The goal is to create the gel in a way that traps the peptides to prevent an initial burst (early release) of semaglutide molecules, while also allowing for controlled and smooth release of the gel over the course of one month without producing toxic molecules.”
Several hydrogel formulations were tested in vitro to investigate drug release rate, duration of action, and semaglutide load to determine the most suitable candidate.
The researchers found that the hydrogel could be easily injected using an off-the-shelf needle. Additionally, the gel started forming within minutes of mixing, ensuring sufficient time for the injection while minimising spread at the injection site. Thus, the depot is small enough to be comfortable and inconspicuous.
In vitro drug release assessments for all formulations demonstrated extended and constant release rates over a period of 1 to 3 months. The researchers also noted that the release duration could be adjusted by optimizing the hydrogel properties and loading.
The hydrogel-semaglutide formulation was also tested on six laboratory rats. After a single injection of the hydrogel-based therapy, the rats showed limited burst (early release) and regular release over a one-month period.
Importantly, the hydrogel was well tolerated, with no inflammatory reaction over the treatment period.
“Our preclinical results show that it is possible to achieve regular, slow release of semaglutide over one month after a single dose, with limited early release. Next, we will test the hydrogel platform in pigs, as their skin and endocrine systems are most similar to humans. If the pig testing goes well, we will move forward with platform development and expect to begin clinical trials within the next few years,” stated Dr. Mégret.