Abstract
Berberine, a natural isoquinoline alkaloid, has been shown to improve glycemic control, lipid metabolism, and blood pressure regulation. However, its poor bioavailability has limited widespread clinical use. ToBeRock® is a self-emulsifying formulation designed to enhance the bioaccessibility of berberine. This retrospective, real-world pilot study conducted through community pharmacies with pharmaceutical care services aimed to evaluate the metabolic and hemodynamic effects of ToBeRock® in adults with impaired fasting glucose (IFG). Sixty adults with IFG (FPG 100–125 mg/dL) were enrolled through territorial pharmacies offering pharmaceutical services. Patients were retrospectively grouped into two cohorts: a Low-Dose Group (ToBeRock® 1 capsule/day) and a High-Dose Group (ToBeRock® 2 capsules/day). Capillary blood sampling and in-pharmacy blood pressure measurements were recorded at baseline (T0), 4 weeks (T1), and 8 weeks (T2). Evaluated parameters included fasting glucose, HbA1c, lipid profile (total cholesterol, LDL, HDL, triglycerides), systolic and diastolic blood pressure (SBP/DBP), and oxidative stress markers (FORT, FORD). Both cohorts showed statistically significant reductions in fasting glucose (p < 0.001), LDL (p = 0.036 Low-Dose/p = 0.039 High-Dose), and triglycerides (p = 0.012/0.009) after 8 weeks of treatment. The High-Dose Group experienced a greater improvement in HbA1c (−0.26%, p = 0.041) and a mild but statistically significant increase in HDL (p = 0.049). Improvements in oxidative balance were observed with significant reductions in FORT (p = 0.019/0.011), increases in FORD (p = 0.033/0.008), and a favorable shift in the REDOX index (p = 0.012/0.006). Systolic blood pressure decreased by −6.3 mmHg in the Low-Dose Group (p = 0.031) and −7.6 mmHg in the High-Dose Group (p = 0.048), while diastolic pressure dropped by −3.9 mmHg (p = 0.044) and −4.2 mmHg (p = 0.051), respectively. This real-world, retrospective analysis highlights the potential clinical benefit of ToBeRock® in improving glycemic, lipid, oxidative, and hemodynamic profiles. The High-Dose Group demonstrated more consistent and significant results, supporting the dose-responsive efficacy of the bioavailable formulation and the value of pharmacy-based monitoring of nutraceutical interventions.
Introduction
Impaired fasting glucose (IFG), defined as fasting plasma glucose levels between 100 and 125 mg/dL, represents a prediabetic condition associated with increased cardiometabolic risk and a high likelihood of progression to type 2 diabetes mellitus (T2DM). IFG affects a substantial proportion of the adult population worldwide: in 2021, the International Diabetes Federation (IDF) estimated that 319 million people globally had impaired fasting glucose, a figure expected to rise to 454 million by 2045 [1].
Beyond glycemic dysregulation, individuals with IFG frequently present with other components of the metabolic syndrome, including dyslipidemia, abdominal obesity, and elevated blood pressure, which synergistically increase the risk of cardiovascular events [2]. In contemporary clinical settings, the initial identification of IFG frequently occurs within community pharmacy environments [3,4]. These pharmacy-based screening platforms enable opportunistic detection of early dysglycemic states in asymptomatic individuals, particularly during non-targeted cardiovascular risk screening programs [5,6]. Within this paradigm, the territorial pharmacist emerges as a peripheral healthcare sentinel, capable of contributing to the subclinical phenotyping of metabolic risk through the integration of point-of-care biochemical data, anthropometric indices, and patient-reported information. This positioning not only facilitates the prompt identification of latent metabolic dysregulation but also enables the initiation of structured interventions, including nutritional and lifestyle counseling, nutraceutical recommendations based on mechanistic plausibility and clinical evidence, and, where indicated, algorithm-guided referral to primary or specialist medical services [7].
The pharmacist’s role in this context is consistent with the principles of proactive risk stratification, territorial predictive prevention, and translational implementation of precision public health and may constitute a pivotal node in delaying or preventing the transition from IFG to overt glucose intolerance or atherogenic dysmetabolism. In this context, lifestyle intervention remains the cornerstone of IFG management; however, the need for early, non-pharmacologic strategies capable of improving metabolic profiles has stimulated growing interest in functional and nutraceutical approaches [8,9,10].
Among these, berberine, a plant-derived isoquinoline alkaloid, has shown promising results in subjects with IFG and metabolic syndrome [11,12]. Berberine exerts multiple metabolic effects: it improves insulin sensitivity, enhances glucose uptake via AMPK activation, and exerts favorable effects on lipid metabolism and inflammatory markers [13]. Clinical studies have demonstrated its ability to reduce fasting glucose, HbA1c, total cholesterol, and LDL-C in prediabetic individuals [14].
Nevertheless, the therapeutic application of berberine has been historically limited by its poor oral bioavailability, due to low intestinal solubility, efflux by P-glycoprotein, and extensive first-pass hepatic metabolism (Figure 1) [15]. To enhance its clinical effectiveness, ToBeRock®, a high-bioaccessibility formulation based on a self-emulsifying drug delivery system (SEDDS), has been developed. This system promotes micellar dispersion of berberine in the intestinal lumen (Figure 1), improving absorption and systemic exposure. The co-formulation with tocotrienols may further support cellular uptake and antioxidant activity, offering a multi-targeted nutraceutical approach to managing early metabolic dysfunction.
Therefore, the present study aimed to evaluate the metabolic effects of a novel high-bioaccessibility berberine formulation (ToBeRock®), administered at two different dosages, in individuals with IFG. The study was conducted in a real-world, pharmacy-based setting to reflect the practical applicability of nutraceutical interventions in early cardiometabolic risk management.
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Colletti, A.; Citi, V.; Martelli, A.; Pellizzato, M.; Riccardi, E.; Cravotto, G. Real-World Pilot Evaluation of a Novel Bioavailable Berberine Formulation (ToBeRock®) in Subjects with Impaired Fasting Glucose Through Pharmacy-Based Retrospective Study. Sci. Pharm. 2025, 93, 42. https://doi.org/10.3390/scipharm93030042
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