Efficacy and safety of berberine hydrochloride for glycemic control in prediabetic individuals: a double-blind, placebo-controlled, and randomized trial

Abstract

Abstract Background: Prediabetes and diabetes involve alterations in glucose homeostasis, including elevated fasting blood glucose and impaired glucose tolerance. Berberine has been identified as a potential regulator of glucose homeostasis with implications on the management of type 2 diabetes mellitus (DM). Given a paucity of data on berberine in prediabetes, evaluation of its effect in prediabetic individuals may prove clinically valuable. The present study aimed to investigate the effect of daily oral berberine on markers of glycemic control and insulin resistance among prediabetic individuals. Methods: A randomized, double-blinded, placebo-controlled trial was conducted for 12 weeks among 34 prediabetic individuals as defined by the American Diabetes Association (fasting plasma glucose (FPG) between 5.6 and 6.9 mmol/L, glycosylated hemoglobin (HbA1c) between 5.7% and 6.4%, or 2-hour 75-gram oral glucose tolerance test (2h-OGTT) between 7.8 and 11.1 mmol/L). HIMABERB® 500 mg was given three times daily to the treatment group, and placebo was administered three times daily to the control group. Glycemic control markers and physical parameters were evaluated for both groups on days 0, 28, 56, and 84. The glycemic control markers assessed included FPG, fasting insulin (FI), 2h-OGTT, HbA1c, and homeostatic model assessment-insulin resistance (HOMA-IR). The observed outcomes were analyzed using independent t-test statistics to determine the significance of differences over time after treatment initiation and between treatment and control groups. Results: Significant decreases in all markers of glycemic control were observed in the treatment group at intermediate time points and the endpoint of the study compared to baseline levels and to the control group. For the treatment group, FPG decreased from 6.75 ± 0.23 mmol/L to 5.33 ± 0.28 mmol/L, FI from 9.81 ± 0.36 to 7.88 ± 0.52 mmol/L, 2h-OGTT from 10.44 ± 0.52 to 8.12 ± 0.40 mmol/L, HbA1c from 6.40% ± 0.20% to 5.43% ± 0.21%, and HOMA-IR from 3.61 ± 0.31 to 2.41 ± 0.14. The decreases in glycemic control markers compared to the control group were clinically and statistically significant (p<0.00001). No severe adverse effects, kidney or liver toxicity were detected. Conclusion: After 12 weeks, berberine (HIMABERB®) intervention in prediabetic individuals significantly reduced glycemic control markers, with mean FPG and 2h-OTGG being reduced to below prediabetic thresholds, supporting the investigation of the use of HIMABERB® for delaying progression to diabetes mellitus. Trial registration: http://ctri.nic.in (CTRI/2021/12/038751) 20/12/2021