The Efficacy and Safety of DLBS3233, A Combined Bioactive Fraction of Cinnamomum burmanii and Lagerstroemia speciosa Plants on The Endocrine-Metabolic Profile of Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial

Background: A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recentlybeen used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leadingto metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This studyevaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. Materials and Methods: This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study overa 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis ModelAssessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductiveparameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver andrenal function, and adverse events. Results: After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidenceinterval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline.On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in theDLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolvedby the end of the study. Conclusion: Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin-XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin-XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).