Glucagon-like peptide-1 (GLP-1) receptor agonists have become central agents in medical weight management and in treating obesity-related conditions. This first-in-human study examined TE-8105, a long-acting GLP-1 receptor agonist, to characterize its pharmacokinetics (PK), preliminary pharmacodynamics (PD), and safety profile in overweight or obese adults without type 2 diabetes mellitus (T2DM).
The investigation used an open-label design with both single-ascending and multiple-dose cohorts. Four single-ascending-dose cohorts (Part A: A1–A4) received single subcutaneous doses of TE-8105 at 0.5, 0.75, 1.5, and 3.0 mg, respectively. Two multiple-dose cohorts (Part B) evaluated repeat dosing every two weeks (Q2W) via subcutaneous injection: B1 received a flat dosing regimen of 1.0 mg Q2W for five doses, and B2 received a titration regimen consisting of a sequence of increasing doses (2 × 1.5 mg, 2 × 2.0 mg, 2 × 2.5 mg, and 3 × 3.0 mg Q2W). Assessments combined in-patient and out-patient visits.
The abstract does not report participant counts for each cohort or detailed demographic characteristics; those details are not provided in the source abstract and therefore cannot be summarized here.
TE-8105 demonstrated a terminal half-life of approximately 120 hours, supporting potential for less frequent subcutaneous administration compared with some currently available GLP-1 receptor agonists. In the flat multiple dosing cohort (B1), there was no observed accumulation. In contrast, the titration multiple dosing cohort (B2) showed measurable accumulation: mean (SD) accumulation ratios after titration were 3.75 (0.86) for Cmax and 3.00 (0.65) for AUC. Plasma concentration–time profiles for single and multiple dosing were reported in graphical form in the full text, illustrating the PK behavior across dose levels and schedules.
A preliminary pharmacodynamic signal was observed for weight change in the titration cohort. Mean percent decrease in body weight from baseline to the end-of-study visit for the titration dosing group was 2.06%. Within that titration cohort, 4 of 8 participants maintained weight loss of ≥5% at study end. The abstract provides these group-level weight-change data for the titration schedule; additional efficacy endpoints or time-course details beyond what is stated were not reported in the abstract.
Treatment-emergent adverse events (TEAEs) that investigators attributed to TE-8105 were consistent with the known mechanism of GLP-1 receptor agonists and demonstrated dose dependence. Reported treatment-related TEAEs included:
Overall, TE-8105 was described as safe and well tolerated in the studied population based on the reported adverse event profile in the abstract. The conflict of interest statement notes several authors were employees of the sponsor organizations and one investigator was contracted by the sponsor; one author declared no conflicts.
In this first-in-human study, TE-8105 displayed pharmacokinetic properties—most notably a terminal half-life near 120 hours—that may permit less frequent subcutaneous dosing compared to some existing GLP-1 receptor agonists. Flat Q2W dosing produced no accumulation, while a stepwise titration schedule produced measurable accumulation in Cmax and AUC. A modest mean weight reduction (2.06%) was reported in the titration cohort, with half of those participants achieving sustained ≥5% weight loss by study end (4 of 8 participants). The safety profile was consistent with GLP-1 receptor agonist class effects, primarily gastrointestinal adverse events that were dose-related.
The abstract does not provide full participant demographic data, cohort sample sizes for all groups, detailed statistical analyses, or longer-term efficacy and safety follow-up. Figures and plasma concentration–time profiles are referenced and available in the full-text article, but exact numerical PK parameter tables, detailed adverse event listings by dose, and comprehensive PD endpoints are not included in the abstract text and therefore are not summarized here.
Overall, based on the information reported in the source abstract, TE-8105 showed a PK profile supportive of infrequent dosing and an adverse event profile consistent with the GLP-1 receptor agonist class, with preliminary evidence of weight loss that warrants further investigation in larger, controlled studies.