Semaglutide hydrogel could reduce diabetes shots to once a month

A new drug delivery system can cut the dosing schedule for semaglutide to just once a month, according to new research presented at EASD 2024.

Lead author Dr Claire Mégret, from ADOCIA, said: “Glucagon-like peptide-1 agonist (GLP-1) drugs have transformed type 2 diabetes care, but weekly injections can be burdensome for people.

“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.” 

Semaglutide works by mimicking the hormone GLP-1, and is currently authorised for the treatment of people with type 2 diabetes with insufficient glycaemic control and long-term weight management. 

Clinical studies suggest that adherence to injected semaglutide is 39-67 per cent for people with type 2 diabetes at one year, and 40 per cent for those who take the drug for weight loss. Similarly, adherence to daily oral pill formulations is around 40 per cent at one year.

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 one to three months.

Dr Mégret said: “A small dollop of gel, known as a ‘depot,’ of the semaglutide-laden hydrogel is injected under the skin.

“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. 

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, 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 one to three months.

The researchers also found that the release duration could be tailored through optimisation 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.

Dr Mégret said: “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.”

Dr Mégret added: “If that goes well, we will move forward the platform development by expecting clinical trials within the next few years.”