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.

New research presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain, showed that consuming fruit, oats, and rye in childhood is associated with a higher risk of developing type 1 diabetes (T1D). On the other hand, eating berries is linked to a lower likelihood of developing the condition. T1D is an autoimmune disease in which the immune system attacks and destroys the insulin-producing islet cells in the pancreas, leading to insufficient insulin production to regulate blood sugar levels properly.

The exact trigger for the immune system’s attack is not known but is believed to involve a mix of genetic predisposition and environmental factors like viruses or certain foods. T1D is the most common form of diabetes in children and is on the rise worldwide. The global number of T1D cases is expected to double in just 20 years, from 8.4 million in 2021 to 17.4 million by 2040. Finland has the highest incidence of T1D globally, with 52.2 cases per 100,000 children under the age of 15, which is over five times higher than in the 1950s. Professor Suvi Virtanen, of the Finnish Institute for Health and Welfare in Helsinki, Finland, who led the research, stated, “Type 1 diabetes imposes a significant burden on the patient and their family, requiring lifelong treatment. It can lead to complications such as eye, heart, nerve, and kidney problems, shortened life expectancy, and substantial healthcare costs (around 1 million euros per patient in Finland). The rapid increase in type 1 diabetes in children suggests that environmental factors play a crucial role in the development of the disease. Identifying these factors will provide opportunities to develop strategies to prevent it and its complications.” 

While numerous food items have been linked to the attack on insulin-producing cells and T1D, there is a lack of high-quality evidence from prospective studies, and the existence of a link remains controversial. To address this, Professor Virtanen and colleagues explored whether diet in infancy and early childhood was associated with the development of T1D in thousands of children in Finland. They followed 5,674 children with genetic susceptibility to T1D from birth to the age of six. Food records completed by their parents repeatedly from the age of three months to 6 years provided information on the entire diet. By the age of six, 94 of the children had developed type 1 diabetes, and another 206 developed islet autoimmunity, putting them at a substantially increased risk of developing T1D in the next few years. When considering the entire diet, several foods were found to be associated with a higher risk of developing T1D.

“To the best of our knowledge, this is the first time a child’s entire diet has been considered at the same time,” says Professor Virtanen. The results show that the more fruit, oats or rye children ate, the more their risk of T1D increased. In contrast, eating strawberries, blueberries, lingonberries, raspberries, blackcurrants, and other berries appeared to protect against T1D. The more berries a child ate, the less likely they were to develop T1D. “Berries are particularly rich in polyphenols, plant compounds which may dampen the inflammation that is associated with the development of type 1 diabetes,” says Professor Virtanen.  “On the other hand, fruits may contain harmful substances that don’t occur in berries. For example, berries can be free of pesticides that are found on other fruits.”

Oats, bananas, fermented dairy products (such as yogurts) and wheat were associated with an increased risk of islet autoimmunity, whereas cruciferous vegetables, such as broccoli, cauliflower and cabbage, were associated with decreased risk. All of the associations were independent – they occurred regardless of the other foods eaten. “It is important to find out which factors in these foods are responsible for these associations,” says Professor Virtanen.  “Are the same causative factors or protective factors found in several foods? “If berries are found to contain a particular protective factor, for instance, either that substance or berries themselves could used to prevent T1D.” It is, however, too early to make any dietary recommendations.

Professor Virtanen says: “Many foods of the foods that we found to be associated with increased risk of type 1 diabetes and the disease process are considered part of a healthy diet and it is important that our results are replicated in other studies before anyone considers making changes to their child’s diet.”

“New research, to be presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain (9-13 September), has found that night owls have a higher BMI, larger waists, more hidden body fat, and are almost 50% more likely to develop type 2 diabetes (T2D) than those who go to bed earlier.”

“The lead researcher, Dr. Jeroen van der Velde, from Leiden University Medical Centre in the Netherlands, stated that previous studies have shown that individuals with a late chronotype – meaning they prefer to go to bed late and wake up later – tend to have unhealthy lifestyles. People with late chronotypes are more likely to smoke or have an unhealthy diet, which may explain why they are at a higher risk of obesity and metabolic disorders, including type 2 diabetes.”

“We believe that lifestyle alone cannot entirely account for the link between a late chronotype and metabolic disorders. Furthermore, although it is established that a late chronotype is linked to higher BMI, the extent to which chronotype influences body fat distribution remains unclear.”

In order to learn more, Dr. van der Velde and colleagues conducted a study on over 5,000 individuals as part of the ongoing Netherlands Epidemiology of Obesity study. They looked into the connection between sleep timing, Type 2 Diabetes (T2D), and body fat distribution to understand how body fat influences disease.

The analysis included participants, 54% of whom were female, with an average age of 56 years and an average BMI of 30 kg/m2.

Participants completed a questionnaire about their typical bedtime and waking times, from which the midpoint of sleep (MPS) was calculated.

The participants were then divided into three groups: early chronotype (the 20% of participants with the earliest MPS), late chronotype (the 20% of participants with the latest MPS), and intermediate chronotype (the remaining 60% of participants).

Waist circumference and BMI were measured for all participants. MRI scans and MR spectroscopy were used to measure visceral and liver fat in 1,526 participants.

The participants were followed up for a median of 6.6 years, during which 225 were diagnosed with T2D.

Here is the revised text:”The results, which were adjusted for age, sex, education, total body fat, and a range of lifestyle factors (physical activity, diet quality, alcohol intake, smoking, and sleep quality and duration), showed that compared with an intermediate chronotype, participants with a late chronotype had a 46% higher risk of T2D.”

This suggests that the increased risk of type 2 diabetes in late risers cannot be solely attributed to lifestyle factors.

“We believe that other mechanisms are also at play,” says Dr. van der Velde. “A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society. This misalignment can lead to metabolic disturbances and ultimately, type 2 diabetes.”

The team also looked at T2D risk in early chronotypes. 

“We expected early chronotypes to have a similar risk of developing type 2 diabetes as intermediate chronotypes,” said Dr. van der Velde. “Our results showed a slightly higher risk, but it was not statistically significant.”

The results also indicated that individuals with a late chronotype had a 0.7 kg/m2 higher BMI, a 1.9 cm larger waist circumference, 7 cm2 more visceral fat, and 14% higher liver fat content, in comparison to those with an intermediate chronotype.

Dr. van der Velde concludes, “Individuals with a late chronotype seem to have a higher risk of developing type 2 diabetes compared to those with an intermediate chronotype. This may be due to higher levels of body fat, including increased visceral and liver fat.”

“The next step is to study if individuals with a late chronotype experience improvements in metabolic health when they adjust the timing of their lifestyle habits.”

“We are currently part of the TIMED consortium, which is examining the complex interplay of the timing of sleep, food intake, and physical activity in relation to type 2 diabetes. Our previous research has demonstrated the importance of the timing of physical activity in relation to insulin resistance.”

“If you have a tendency to stay up late, you may be more inclined to eat later in the evening,” says Dr. van der Velde. “Although our study didn’t directly measure this, there is increasing evidence that limiting the times when you eat, for example, not eating anything after a certain time like 6 pm, could have metabolic benefits.”

“Night owls concerned about the increased risk of type 2 diabetes may want to avoid eating late in the evening, at least.”

“The evidence isn’t there yet, but we aim to provide specific advice on the timing of lifestyle behavior in the future.”