Context: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate antimetabolic and antisarcopenic effects in Cushing's syndrome (CS) and autonomous cortisol secretion (ACS) patients. Objective: To confirm the efficacy and safety of S-707106 (11β-HSD1 inhibitor) administered to CS and ACS patients. Design: A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database. Setting: Kyushu University Hospital, Kurume University Hospital, and related facilities. Patients: Sixteen patients with inoperable or recurrent CS and ACS, with mildly impaired glucose tolerance. Intervention: Oral administration of 200 mg S-707106 after dinner, daily, for 24 weeks. In patients with insufficient improvement in oral glucose tolerance test results at 12 weeks, an escalated dose of S-707106 (200 mg twice daily) was administered for the residual 12 weeks. Main Outcome Measures: The rate of participants responding to glucose tolerance impairment, defined as those showing a 25% reduction in the area under the curve (AUC) of plasma glucose during the 75-g oral glucose tolerance test at 24 weeks. Results: S-707106 administration could not achieve the primary endpoint of this clinical trial (>20% of responsive participants). AUC glucose decreased by -7.1% [SD, 14.8 (90% CI -14.8 to -1.0), P=0.033] and -2.7% [14.5 (-10.2 to 3.4), P=0.18] at 12 and 24 weeks, respectively. S-707106 administration decreased AUC glucose significantly in participants with a high body mass index. Body fat percentage decreased by -2.5% [1.7 (-3.3 to -1.8), P<0.001] and body muscle percentage increased by 2.4% [1.6 (1.7 to 3.1), P<0.001]. Conclusions: S-707106 is an effective insulin sensitizer and antisarcopenic and antiobesity medication for these patients.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical