Abstract
Context
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate anti-metabolic and anti-sarcopenic 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 BID) 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– -1.0], P=0.033) and -2.7% (14.5 [-10.2–3.4], 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– -1.8], P<0.001), and body muscle percentage increased by 2.4% (1.6 [1.7–3.1], P<0.001).
Conclusions
S-707106 is an effective insulin sensitizer and anti-sarcopenic and anti-obesity medication for these patients.
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