One Injection of Semaglutide or Tirzepatide Could Last Over 6 Weeks With New Hydrogel Technology | Research

The takeaway

A hydrogel depot formulation delivers semaglutide or tirzepatide from a single injection for over 6 weeks, matching the blood sugar and weight benefits of daily injections in diabetic rats.

One injection, 6+ weeks of effect
A single hydrogel depot injection maintained therapeutic semaglutide or tirzepatide levels for over 6 weeks in diabetic rats, with equivalent blood sugar and weight control to daily injections.

What the researchers found

A single injection of hydrogel-based depot formulations of either semaglutide or tirzepatide maintained therapeutic drug levels for over 6 weeks in a rat diabetes model. These single-dose formulations were equally effective at controlling blood glucose and body weight as daily injections of the same drugs in standard formulations. The hydrogel depot technology is easy to manufacture, injectable, and biocompatible, potentially enabling months-long treatment intervals.

Why it matters

Current GLP-1 drugs require weekly injections, which many patients find burdensome and leads to poor adherence. A single injection lasting 6+ weeks — or potentially months — could dramatically improve patient compliance and outcomes. For the millions of people who need these peptide drugs but struggle with regular injections, this technology could be transformative.

The numbers in context

Single injection · >6 weeks drug release · equivalent to daily injections for glucose control and weight · both semaglutide and tirzepatide formulated · rat diabetes model · injectable hydrogel depot · excellent biocompatibility

How the study worked

Researchers developed injectable hydrogel depots loaded with semaglutide or tirzepatide. The formulations were tested in a rat model of diabetes. Drug levels were measured over 6+ weeks after a single injection. Blood glucose regulation and body weight were compared between single hydrogel depot injections and daily standard injections of the same drugs.

Who was studied

Rat model of diabetes treated with hydrogel depot formulations of semaglutide and tirzepatide

What this study cannot tell us

This is a preprint (bioRxiv) that has not yet undergone peer review. The study used a rat model; pharmacokinetics in larger animals and humans may differ significantly. The 6-week release window, while impressive, has not been confirmed in primates or humans. Manufacturing scale-up and regulatory pathway for a hydrogel depot GLP-1 formulation would be complex. Whether steady-state drug levels from a depot formulation produce the same clinical effects as pulsed weekly dosing is unknown.

How to read the evidence

This is a preprint (not yet peer-reviewed) reporting preclinical data from a rat diabetes model. While the concept is promising and the results are encouraging, the study needs peer review, validation in larger species, and eventual human clinical trials.

When this study was published

Published as a 2025 preprint (bioRxiv), this represents cutting-edge drug delivery technology that could reshape how GLP-1 peptide drugs are administered.

The bigger picture

As GLP-1 drugs become standard treatment for millions with diabetes and obesity, improving convenience is a major priority. This hydrogel technology could be as significant as the transition from daily to weekly dosing that made semaglutide a blockbuster. Monthly or bi-monthly formulations would further reduce injection burden, improve adherence, and potentially enable clinic-administered treatments that ensure compliance.

Questions still open

Will the hydrogel depot achieve similar release kinetics and efficacy in primates and humans?
Could monthly dosing reduce the gastrointestinal side effects associated with GLP-1 drugs by providing steadier drug levels?
How does the depot formulation affect the pharmacodynamic response compared to the natural peak-and-trough pattern of weekly injections?

Common questions

How does the hydrogel depot work?

The hydrogel is a special injectable gel material that encapsulates semaglutide or tirzepatide. Once injected under the skin, it forms a depot (reservoir) that slowly releases the peptide drug over weeks. The gel gradually dissolves as it releases the drug, eventually being completely absorbed by the body. This controlled release maintains steady therapeutic drug levels without the peaks and troughs of repeated injections.

When might this be available for patients?

This technology is still in early preclinical development (tested in rats). Before reaching patients, it would need testing in larger animals, safety studies, and human clinical trials — a process that typically takes several years. However, since the drugs themselves (semaglutide and tirzepatide) are already approved, the regulatory pathway may be somewhat faster than for an entirely new drug.

Read the original research

Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight.

bioRxiv : the preprint server for biology

View on PubMed ↗Publisher’s paper ↗

Citation

d'Aquino, Andrea I; Dong, Changxin; Nguyen, Leslee T; Yan, Jerry; Jons, Carolyn K; Saouaf, Olivia M; Song, Ye Eun; Eckman, Noah; Kapasi, Sara; Williams, Christian Milton; Doulames, Vanessa Madelyn; Sen, Samya; Manna, Manoj K; Alakesh, Alakesh; Lu, Katie; Hall, Ian; Appel, Eric A. (2025). Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.07.02.662867