Long-acting management of diabetes and associated complications using an injectable thermosensitive hydrogel incorporating IgG-conjugated GLP-1RA

Sep 28, 2026

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has improved diabetes care, yet frequent dosing remains difficult. A sustained-release, hydrogel-based delivery system was developed for Efsubaglutide Alfa (Suba), an IgG-conjugated GLP-1RA, aiming to reduce treatment burden and improve adherence. Biodegradable PLGA-PEG-PLGA thermosensitive hydrogel was engineered and evaluated via pharmacokinetics and pharmacodynamics in multiple rodent models, producing multi-week release, stable glycemic control, enhanced insulin secretion, improved pancreatic function, and mitigation of diabetes-related complications.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Abstract

Rationale

Methods

Results

Conclusions

Introduction

Theranostics 2026, Vol. 16, Issue 4 1833 Ivyspring International Publisher Theranostics 2026; 16(4): 1833-1854. doi: 10.7150/thno.120844 Research Paper Long-acting management of diabetes and associated complications using an injectable thermosensitive hydrogel incorporating IgG-conjugated GLP-1RA Hancheng Wang1, Zhiyong Chen1, Siyi Gu1, Yaoben Wang1, Yang Wang1, Caiyun Gao1, Jiayue Shi1, Jiandong Ding1, Qinghua Wang2,3,􀀍, Lin Yu1,􀀍 1. State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China. 2. Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai 200040, China. 3. Innogen Pharmaceutical Technology Co., Ltd., Shanghai 201203, China. 􀀍 Corresponding authors: E-[mail address: qh_wang@fudan.edu.cn](mail address: qh_wang@fudan.edu.cn) (Q. Wang) [and yu_lin@fudan.edu.cn](and yu_lin@fudan.edu.cn) (L. Yu) . © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2025.07.02; Accepted: 2025.10.27; Published: 2026.01.01 Abstract | Rationale: The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has advanced diabetes management. Nevertheless, frequent administration remains a challenge, even with weekly formulations. Herein, we developed a sustained-release hydrogel-based delivery system for Efsubaglutide Alfa (Suba), an IgG-conjugated GLP-1RA, designed to alleviate treatment burden and enhance patient adherence.
Methods: A series of biodegradable poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)(PLGA-PEG-PLGA) triblock copolymers were synthesized, and a thermosensitive PLGA-PEG-PLGA hydrogel with suitable sol–gel transition temperature and in vivo degradation profile was selected for the fabrication of the Suba-loaded hydrogel system (Suba@T-gel). The pharmacokinetic and pharmacodynamic profiles following subcutaneous administration of Suba@T-gel were evaluated in multiple rodent models.
Results: In vivo non-invasive imaging and pharmacokinetic studies showed that a single subcutaneous injection of Suba@T-gel enabled sustained release of Suba for over three weeks. This prolonged release profile is attributed to moderate Suba-polymer interactions and the large molecular size of Suba, which facilitate sustained drug release through a carrier degradation-controlled mechanism. In diabetic murine models, a single administration of Suba@T-gel achieved stable glycemic control for three weeks. Furthermore, the continuous liberation of Suba remarkably enhanced insulin secretion, reduced glycosylated hemoglobin levels, and improved pancreatic function in diabetic mice. Additionally, this system ameliorated diabetes-related complications by improving lipid metabolism, reversing hepatic steatosis and enhancing nerve fiber density.
Conclusions: The Suba@T-gel system represents a promising strategy for long-acting management of diabetes and substantial improvement in patient compliance. | | | --- | --- | | Keywords: type 2 diabetes mellitus; glucagon-like peptide-1 receptor agonists; injectable hydrogel; long-acting formulation; glycemic control
Introduction | | | Diabetes mellitus, which has emerged as one of the most critical public health challenges of our era, is a chronic endocrine and metabolic disorder characterized by persistent hyperglycemia and a myriad of associated complications, such as cardiovascular disease, neuropathy and nephropathy [1-3] . According to the International Diabetes Federation (IDF), more than 500 million people worldwide are currently afflicted with diabetes, with | type 2 diabetes mellitus (T2DM) accounting for over 90%

FAQs

What problem does the study address in diabetes treatment?

Frequent administration of GLP-1 receptor agonists remains challenging, even with weekly formulations, due to treatment burden and adherence issues.

How is the long-acting delivery system designed?

A thermosensitive PLGA-PEG-PLGA hydrogel was selected and used to fabricate a Suba-loaded system (Suba@T-gel) for sustained drug release after subcutaneous injection.

What benefits were observed in diabetic animal models?

A single Suba@T-gel administration provided sustained release for over three weeks, achieved stable glycemic control, enhanced insulin secretion, reduced glycosylated hemoglobin, improved pancreatic function, and ameliorated diabetes-related complications including lipid metabolism and hepatic steatosis.

Sep 28, 2026

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