Journal of medicinal chemistryMar 5, 2025

New Dual Fatty Acid-Linked GLP-1 Drug TE-8105 Shows Better Effects on Diabetes, Obesity, and Liver Disease Than Semaglutide

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

TE-8105 demonstrates improved long-term glycemic control and weight loss compared to semaglutide in diabetic mice.

Conjugating two fatty acids to peptide drugs may enhance their pharmacokinetics and therapeutic effects.
The multiarm linker technology allows for precise control of fatty acid spacing, composition, and attachment to peptides.
TE-8105 showed better performance than semaglutide in promoting weight loss and improving liver health in diabetic mice.
In obese mice, TE-8105 resulted in dose-dependent weight loss and favorable changes in body composition.
TE-8105 may reduce liver fat and improve liver health in mice with nonalcoholic steatohepatitis.

Simplified

Conjugating two fatty acids (2FAs) to peptide drugs can improve pharmacokinetics and therapeutic effects. However, optimizing FA spacing, chain combination, and attachment site to simultaneously enhance albumin binding and drug efficacy remains challenging. We introduce a multiarm linker technology enabling precise control of 2FA spacing, composition, and attachment. By applying this technology to a modified glucagon-like peptide-1 (GLP-1) and screening various 2FA-GLP-1 conjugates differing in linkage, linker, and FA properties for improved albumin affinity, pharmacokinetics, and pharmacodynamics, TE-8105 emerged as a promising candidate. TE-8105 outperformed semaglutide, showing improved long-term glycemic control, weight loss, and liver health in diabetic mice, and dose-dependent weight loss and favorable body composition changes in obese mice. A distinct advantage of TE-8105 over semaglutide is its low-dose reduction of liver steatosis and improvement of liver health in nonalcoholic steatohepatitis mice. The multiarm linker technology provides a versatile platform for developing improved 2FA-peptide therapeutics.

Key numbers

7.8×

Potency Increase

TE-8105's EC value compared to semaglutide.

16.3 ± 3.9%

Weight Loss Reduction

Weight loss percentage at 100 dose.

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Funding

Competing interests

The authors declare the following competing financial interest(s): M.-T. Wong, J. D. Wright, P.-H. Lin, and H.-M. Chu are employees of Immunwork, Inc. W.-C. Lin, H.-J. Lee, C.-J. Peng, and H.-M. Chu are employees of T-E Meds, Inc. T-W Chang is the founder of Immunwork, Inc. and T-E Meds, Inc., and C. Lim is scientific advisor to both companies. All authors hold stock or have stock options from Immunwork, Inc. or T-E Meds, Inc.

PubMed

New Dual Fatty Acid-Linked GLP-1 Drug TE-8105 Shows Better Effects on Diabetes, Obesity, and Liver Disease Than Semaglutide

Abstract

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Competing interests

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Abstract

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