Title : Efficacy and safety of Gamitaeeumjowee-tang (Nubebe Gambijeong) in the treatment of obesity: An integrated analysis of two real world cohorts comprising 117,306 patients
Abstract:
Background: Gamitaeeumjowee-tang, a Sasang constitutional formula containing Ephedra Herba 16 g/day, is one of the most widely prescribed herbal medicines for obesity in Korean medicine. Ephedrine-type alkaloids suppress appetite and increase thermogenesis, but the same sympathomimetic mechanism underlies palpitations, tremor, insomnia and thirst. Real-world evidence — particularly on whether adverse event (AE) risk varies with patient age has remained limited.
Objectives: To quantify the weight-reduction effectiveness of tablet-form Gamitaeeumjowee-tang in routine primary care, to characterize its AE profile using standard pharmacovigilance instruments, and to determine whether AE frequency and symptom composition differ across age groups.
Methods: Two independent real-world cohorts were analyzed. Cohort A was a multicenter retrospective chart review of 3,491 adults with a BMI ≥ 23 kg/m² treated at four Korean medicine clinics (September 2017–August 2018); body weight, body composition (InBody 370) and blood pressure were assessed at weeks 2–4, 6–8 and 10–12, with missing data imputed by last observation carried forward (LOCF). Cohort B comprised 113,815 patients prescribed a Gambijeong-series formulation across a nationwide clinic network (August 2021–May 2024), with AEs captured by structured surveys at day 2 and week 2 plus continuous self-reporting. AEs were coded by WHO-ART System Organ Class, causality assessed by the WHO-UMC algorithm and severity by NCI-CTCAE v5.0. Paired t-tests, Pearson correlation and the Cochran–Armitage trend test were applied; age-specific rates were computed against two denominators.
Results: At weeks 10–12, mean weight loss was 8.73 ± 3.74%; 68.0% of patients had lost ≥ 5% and 20.5% ≥ 10% of baseline weight. In the body-composition subgroup (n = 814), fat mass fell by 6.51 ± 4.85 kg (−18.4%) while skeletal muscle mass declined by only 0.67 ± 3.33 kg (−2.4%), fat accounting for 84.2% of the weight lost. Systolic and diastolic blood pressure decreased by 4.70 ± 13.93 and 1.93 ± 11.29 mmHg (all p < 0.001). AE reporting declined from 47.28% at weeks 2–4 to 25.33% at weeks 10–12; approximately 99% of events were CTCAE grade 1 and none were grade 4 or 5. In Cohort B, AE frequency showed no age trend against all prescribed patients (day 2, z = −0.27, p = 0.786); the trend apparent among respondents reflected selective response bias, response rates falling from 38.8% (≤ 19 years) to 11.9% (≥ 60 years). Symptom composition shifted consistently with age: palpitations (39.1% to 20.4%) and hand tremor (28.1% to 18.0%) decreased, whereas insomnia (10.0% to 44.2%) and constipation (7.1% to 20.1%) increased (all p < 0.001). All six severe AEs (grade ≥ 3; 0.007%) occurred in patients aged 22–49 years and none were causally related.
Conclusions: Tablet-form Gamitaeeumjowee-tang produced clinically meaningful, muscle-sparing weight reduction that met international efficacy thresholds for anti-obesity pharmacotherapy within 12 weeks, and lowered blood pressure. Adverse events were predominantly mild, self-limiting and diminished with continued use. Age altered symptom composition but not overall AE risk, supporting age-differentiated counseling rather than age-stratified safety grading. The absence of a control group and reliance on self-reported AEs remain key limitations.
