Safety, pharmacokinetics and pharmacodynamics of Efsubaglutide Alfa in healthy participants: A randomised, dose‐escalation phase 1 study

Jun 5, 2025Diabetes, obesity & metabolism

Safety and body effects of increasing doses of Efsubaglutide Alfa in healthy adults

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Abstract

A total of 48 healthy adults participated in a Phase 1 study evaluating the safety and effects of Efsubaglutide Alfa.

Efsubaglutide Alfa showed dose-proportional exposure, with a median time to peak concentration of 47.5-71.7 hours and a mean half-life of 121.4 hours.
No serious adverse events were reported; mild-to-moderate gastrointestinal issues were the most common side effects.
Fasting plasma glucose levels transiently decreased after dosing, returning to baseline by Day 2 and fluctuating within expected physiological variability through Day 28.
Oral glucose tolerance tests indicated reduced glucose excursions in recipients of Efsubaglutide Alfa compared to placebo.
Weight loss was observed, peaking at 4.0% by Days 4-7 at the higher dose, with gradual return towards baseline by Day 28.

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AIMS: This Phase 1 study aimed to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose subcutaneous Efsubaglutide Alfa, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants.

MATERIALS AND METHODS: This randomised, double-blind, placebo-controlled, single-dose escalation study was conducted at a single centre. A total of 48 healthy adults were randomised (6:2) across six dose cohorts (0.375, 0.75, 1.5, 3, 6 and 9 mg) to receive Efsubaglutide Alfa or placebo. Safety, PK and PD parameters were assessed.

RESULTS: Efsubaglutide Alfa exhibited dose-proportional PK, with a median Tof 47.5-71.7 h and a mean half-life (T) of 121.4 h. Exposure increased linearly across doses (C: 37.1-832.4 ng/mL, AUC: 8699.6-193446.6 ng/mL·h). No serious AEs occurred; mild-to-moderate gastrointestinal AEs (nausea, vomiting, decreased appetite) were the most common in Efsubaglutide Alfa-treated subjects. Post-dose, fasting plasma glucose transiently declined on Day 1, returned to baseline by Day 2, and remained within -0.8 to +1.9 mmol/L relative to baseline (within expected physiological variability) through Day 28. Fasting insulin and C-peptide levels slightly increased on Day 1, normalised by Day 2, and remained stable. At Day 2, OGTT revealed reduced glucose excursions in Efsubaglutide Alfa recipients (p = 0.0150 vs. placebo; AUC ~0.7 mmol/L·2 h lower), while insulin and C-peptide levels remained unchanged. Dose-dependent weight loss peaked at Day 4-7, with up to a 4.0% reduction (p < 0.0001) at the higher dose, followed by a gradual return towards baseline by Day 28. max1/2max0-∞

CONCLUSIONS: Efsubaglutide Alfa was well tolerated in healthy participants, with a favourable PK and PD profiles that support further clinical development in type 2 diabetes and metabolic disorders.

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Safety, pharmacokinetics and pharmacodynamics of Efsubaglutide Alfa in healthy participants: A randomised, dose‐escalation phase 1 study

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