Researchers in France have developed a once-a-month hydrogel-based delivery system for semaglutide, significantly simplifying diabetes and weight management treatment.
The new system maintains steady drug levels, enhancing efficacy and safety, with promising initial results paving the way for upcoming clinical trials.
Innovative Diabetes / Weight Loss Treatment
French researchers have developed a new drug delivery system that could cut the dosing schedule for the type 2 diabetes and weight control drug semaglutide to just once a month, according to new research to be presented at this year’s annual meeting of The European Association for the Study of Diabetes (EASD) in Madrid, Spain.
“Glucagon-like peptide-1 agonist (GLP-1) drugs have transformed type 2 diabetes care, but weekly injections can be burdensome for patients. A single shot a month could make it much easier for people living with diabetes or obesity to stick to their drug regimens, improving quality of life and reducing side effects and diabetes complications,” said lead author Dr. Claire Mégret from ADOCIA, Lyon, France, the biotechnology company who developed the hydrogel.
Semaglutide, marketed as Ozempic, Rybelsus, and Wegovy, is a GLP-1 receptor agonist that helps to regulate blood sugar levels and promote weight loss. This medication is especially effective in managing type 2 diabetes and is available in both injectable and oral forms. Semaglutide enhances the body’s natural ability to control blood glucose and reduce appetite, providing a dual approach to treatment.
Semaglutide works by mimicking the hormone glucagon-like peptide 1 (GLP-1), and is currently authorized for the treatment of type 2 diabetes patients with insufficient glycaemic control and long-term weight management.
Clinical studies suggest that adherence to injected semaglutide is 39-67% for type 2 diabetes patients at one year, and 40% for patients who take the drug for weight loss. Similarly, adherence to daily oral pill formulations is around 40% at one year.
Innovations in Drug Delivery Systems
Long-acting delivery formulations could increase drug efficacy and safety by maintaining steady drug levels in the body at optimal concentrations.
The new hydrogel delivery platform uses two innovative degradable polymers that are chemically bound to one another to form a gel, but allow slow, sustained release of soluble peptides over 1 to 3 months.
“A small dollop of gel, known as a ‘depot,’ of the semaglutide-laden hydrogel is injected under the skin,” explained Dr. Mégret. “The challenge is to formulate the hydrogel to entrap the peptides to limit initial burst (early release) of semaglutide molecules and, at the same time, to allow smooth release and controlled dissolving of the gel over one month, without generating toxic molecules.”
Several formulations of the hydrogel were tested in vitro to investigate the drug release rate, duration of action, and semaglutide load to define the best candidate.
Promising Pre-Clinical Results
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 minimizing spread at the injection site, so that the depot is small enough to be comfortable and inconspicuous.
In vitro drug release assessments for all formulations showed extended and constant release rates over 1 to 3 months. The researchers also found that the release duration could be tailored through optimization of the hydrogel properties and loading.
The hydrogel-semaglutide formulation was also tested in six laboratory rats. In the rats, a single injection of the hydrogel-based therapy, showed limited burst (early release) and a regular release over a one-month period.
Importantly, the hydrogel was well tolerated with no inflammatory reaction over the treatment period.
“Our pre-clinical results demonstrate that the regular, slow release of semaglutide over one month after administering a single dose, with limited early release, is achievable. Next, we will be testing the hydrogel platform in pigs, whose skin and endocrine systems are most similar to those in humans. If that goes well, we will move forward the platform development by expecting clinical trials within the next few years,” said Dr. Mégret.
Meetings: Annual Meeting of the European Association for the Study of Diabetes (EASD)