Efficacy and Safety of an Ayurveda Herbal Formulation in Uncomplicated Type 2 Diabetes mellitus

Abstract

Background

Medicinal plants and herbal preparations have been used in Ayurveda medicine to treat diabetes for centuries. Link Gluconorm (LG) is a standardized solid formulation comprising seven medicinal herbs that have been used as herbal ingredients in Ayurveda for treating type 2 diabetes mellitus (T2DM). This study evaluated the efficacy and safety of the solid form of LG, and its effect on the quality of life (QoL) in T2DM patients.

Materials and methods

An observational study was conducted on 37 newly diagnosed uncomplicated T2DM patients aged between 35 and 65 years, whose fasting blood glucose levels ranged between 110 and 160 mg/dL. They were being treated for diabetes using the LG herbal formulation as the sole treatment. Laboratory tests for assessing glycemic control and safety were done at baseline and repeated at 4-weekly intervals for 24-weeks. A validated diabetes-specific QoL inventory was administered every 2 weeks.

Results

The mean age was 48 ± 9y, and the mean body mass index was 25.0 ± 4.4 kg/m² and 25.2 ± 4.2 kg/m² for females and males, respectively. Statistically significant reductions in mean fasting blood glucose (153.85 mg/dL ± 15.62 to 129.01 mg/dL ± 12.88, p = 0.006), postprandial blood glucose (191.27 mg/dL ± 21.40 to 140.72 mg/dL ± 8.92, p < 0.001), glycosylated hemoglobin (8.51%±0.44 to 7.43%±0.40, p < 0.001) and improved QoL scores (1.93 ± 0.22 to 1.55 ± 0.08, p < 0.01) were observed at 24 weeks. There were no adverse changes in the hematological, liver and renal function safety parameters assessed using laboratory investigations. No adverse events or hypoglycemia were reported.

Conclusions

The polyherbal formulation LG significantly improved the QoL and glycaemic parameters and appeared safe after 24 weeks of treatment. Due to the small sample size, unblinded nature of this preliminary study, and the lack of a control arm, a randomized double-blinded controlled clinical trial on a larger group of patients is recommended.

Keywords

ayurveda type 2 diabetes efficacy polyherbal quality of life safety

Introduction

Diabetes and its Global Impact on Morbidity and Mortality

Diabetes is a chronic, non-communicable disease caused by a defect in insulin secretion by the pancreas or an ineffective use of insulin by the human body.¹ These abnormalities in the secretion and utilization of insulin increase the blood glucose, which leads to malfunctioning of the heart, eyes, kidneys, and nerves.² There are two types of diabetes: type 1 and type 2. Type 1 diabetes (juvenile-onset diabetes) occurs most frequently in children and adolescents, whereas type 2 diabetes (T2DM) is more common in adults. T2DM accounts for about 90% of all diabetes worldwide.¹ About 422 million people worldwide have diabetes, with the majority living in low- and middle-income countries, and over 1.5 million deaths are directly attributed to diabetes annually.² The age-adjusted diabetes prevalence in Southeast Asia was 10.0%, a prevalence close to North America's prevalence of 11.9%.¹ The prevalence of diabetes has increased in low- and middle-income countries at a much faster rate than in high-income countries.³ lifestyle modifications, screening for diabetes, insulin therapy, and oral antidiabetic medications (biguanides, sulfonylureas, meglitinides, thiazolidinediones, α-glucosidase inhibitors, dipeptidyl peptidase-IV inhibitors, etc) are the primary and secondary health strategies used for preventing complications related to diabetes.

Despite the availability of these medications, for the management of hyperglycemia in patients with T2DM, the growing impact of diabetes and its associated complications leads to one death per eight seconds.¹ Among these, metformin is the first-line treatment used for treatment of early diabetes, and its’ use is reported to result in gastrointestinal disturbances including diarrhea, nausea, and dyspepsia in about 30% of subjects.⁴ As such, there is a need for alternative medications, and herbal medicines that have been used for centuries are potential options.

Ayurveda Medicine and Polyherbal Treatment

Ayurveda medicine, which originated in India, is a prominent parallel medical system that is being practiced all over the world, but predominantly in Asian countries. Herbal medications have been used predominantly by many Asian societies for a variety of disorders for several centuries. With regard to the treatment of diabetes, medicinal plants and their herbal preparations have been used by physicians practicing traditional medicine over a long period.⁵ Evidence on the safety and efficacy of a variety of mono- and poly-herbal preparations for diabetes has been established in several in-vitro and in-vivo models, and in a few clinical trials, although data on their effectiveness is limited.⁶ Chemical compounds with anti-diabetic properties, too, have been isolated from some of these plants in laboratory studies.⁷

Allopathic medicine remains the main stream medicine, and T2DM patients are treated with refined drugs where the active component has been identified and found to be effective through randomized clinical trials (RCTs). Unlike allopathic medicine, the alternative medical systems target the whole body to remedy the disequilibrium, and therefore those remedies are often polyherbal.⁸ A study done among members of the American Association of Diabetes Educators has shown that 63% of diabetes educators in the United States of America recommend some type of alternative therapy to their patients.⁹ In a large hospital-based study conducted in Thailand, 37.5% of patients with type 2 diabetes used herbal medications concurrently with allopathic treatment prescribed for diabetes.¹⁰ In a cross-sectional study conducted on 395 diabetic patients visiting the diabetes care service of a state hospital in Ethiopia, 58.5% used herbal medication in addition to the prescribed medicine.¹¹ Significant differences in the outcome scores between treatment and control groups indicate that herbal treatment is significantly better in terms of improving the quality of life in specific domains such as vitality, bodily pain, mental health, general health, and physical functioning when compared to allopathic treatment.¹² Therefore, it is essential that studies are conducted to assess the effectiveness of herbal medications when they are used alone or in combination with allopathic medications.

In ancient Ayurvedic texts, diabetes and its treatment are described under the disease conditions Prameha roga and Madhumeha. In Sanskrit the word “prameha” is derived from ‘pra’ - meaning excess, ‘meha’ - meaning passing urine, and roga meaning diseases, therefore used for defining diseases with increased frequency of urine. Ayurveda texts describe Madumeha as a disease belonging to the Prameha roga category characterized byexcessive passage of urine, sweet in nature,^13,14

A decoction comprising Musa paradisiaca L., Tribulus terrestris L., Phyllanthus emblica L., Salacia reticulata Wight, Santalum album L. and Sida rhombifolia subsp. alnifolia (L.) Ugbor., is used for treating T2DM by Ayurveda practitioners. Some practitioners add a decoction made of Coccinia grandis (L.) Voigt. into this prescription.¹⁵ The seven medicinal plants incorporated in these two decoctions have been converted to a solid form proprietary product, Link Gluconorm (LG), while maintaining the original formulary requirements. The efficacy and safety of this solid form as a medication for T2DM have been investigated in this observational study.

Ethnopharmacological Evidence

Currently available scientific evidence on some of the plant ingredients included in LG, has been individually assessed and has shown significant effectiveness in controlling diabetes mellitus, as described here.

Leaves of Coccinia grandis (L.) Voigt (CG) have been used as a complementary medicine for the management of diabetes. Double-blind placebo-controlled RCTs conducted in India and Sri Lanka with CG extract have shown beneficial effects on fasting and post-prandial blood glucose levels in those treated.^7,16 Cucurbitacins B, and D, Cephalandrol, Cephalandrin A and B and related analogues have been identified as some of the bioactive compounds present in CG extract.⁷ Additionally, beta cell regeneration induced by CG has been demonstrated in alloxan-induced diabetic rats using immunohistochemistry studies of the pancreas.¹⁷ In streptozotocin induced diabetic rats, the oral administration of CG leaf extracts increased hepatic hexokinase and plasma insulin levels, which are responsible for glycolysis. In the same experiment a reduction in the levels of gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6- biphosphatase was reported indicating the possible role of CG in regulating carbohydrate metabolizing enzymes.¹⁸

Salacia reticulata Wight (SR) is a widely used Ayurvedic herb to treat diabetes. RCTs have indicated that SR is effective in reducing fasting blood glucose (FBG), glycated haemoglobin (HbA1c) levels and body mass index (BMI) in patients with T2DM.¹⁷ The alpha-glucosidase inhibitory effect has been identified as the primary mode of action responsible for the hypoglycaemic effect of Salacia reticulata Wight extracts.¹⁹

Stem juice of Musa paradisiaca L. (MP) has been long used as a traditional treatment for diabetes mellitus in several tropical countries.²⁰ A recent study investigated the ethanol extract of MP stem for anti-diabetic activity. The MP extract and its derivatives were shown to inhibit the secretion of alpha -glucosidase and alpha-amylase. These activities alone are inadequate for controlling diabetes and its complications. The inhibition of aldolase reductase that is responsible for dealing with excess glucose spillover and the inhibition of both protein glycation and free radical production are important in the comprehensive control of blood glucose levels and microvascular complications of diabetes, and MP extract was shown to exert all three inhibitory activities in alloxan-induced diabetic rats. These results indicate the potential of MP to be an important therapeutic component in the treatment of diabetes.²¹

Tribulus terrestris L. (TT) is used in many traditional medicine systems, including Iranian, Turkish, Indian, Persian, and Chinese, for the treatment of a variety of diseases, including diabetes mellitus.²² A double-blind, randomized, placebo-controlled clinical trial conducted in women with diabetes to evaluate the effect of the hydroalcoholic extract of TT on serum glucose showed a significant blood glucose-lowering effect in the treated arm compared to the placebo. In addition, the total cholesterol and low-density lipoprotein levels of the TT treated group were significantly lower compared to the placebo group.²² A more recent study on fecal microbiome showed that TT reversed the disordered gut microbiota in diabetic rats. A significant correlation was seen between microbial flora, their metabolites and diabetes related indicators. The microbiome changes in these rats may have contributed to the therapeutic effects of improved glucose and lipid metabolism and remission in insulin resistance.²³

The fruit of Phyllanthus emblica L. (PE) plays an important role in the treatment of T2DM and its metabolic complications. The efficacy of this fruit has been investigated in a few clinical trials and many in vitro and in vivo models. Research studies show Phyllanthus emblica L. exerts its antidiabetic activity by enhancing the function of insulin by reducing insulin resistance, activating the insulin signaling pathway, protecting β-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products.²⁴ Diabetic rats treated with PE fruit extracts have shown an increase in the number and size of pancreatic beta cells in histopathological studies, and ellagic acid was shown to be responsible.²⁵

Santalum album L. (SA) has been used in Morocco to treat diabetic patients, although the mechanism of action of SA has not been described.²⁶

Sida rhombifolia subsp. alnifolia (L.) Ugbor. (SR) has been used in folk medicine for diabetes in many countries, including India, Brazil, and Africa. Its role in regulating blood glucose level have been shown in animal studies, where rats fed with leaf extracts of SR showed an inhibition of α-amylase and α-glucosidase activities, indicating the potential of SR as an antidiabetic medication.^27,28

It is notable that the above-mentioned pharmacological activities have been described with regard to the individual herbal ingredients that comprise the LG formulation. However, the efficacy and safety of the composite polyherbal formulation, LG have neither been proven nor refuted through the use of clinical studies, creating a need to initially conduct either cohort or preliminary observational studies for determining both safety and efficacy.

Diabetes and Quality of Life

The quality of life (QoL) is an important healthcare outcome in the management of many chronic diseases, including diabetes. The QoL of diabetic patients is linked to their adherence to treatment and consequent glycemic control.²⁹ The QoL of patients is generally considered to fall into four categories: physical, psychological, social, and spiritual.³⁰ Studies have indicated that demographic factors such as gender, age, socio-economic status, marital status, and other biological and medication-related factors, such as use of insulin injections, comorbid conditions, and their duration, are associated with QoL.^31,32 A study conducted in an allopathic hospital-based treatment setting in Sri Lanka in a sample of 150 patients with T2DM showed that about 60% of the patients were suffering from physical and psychological sequelae, and half of them were experiencing limitations in continuing social relationships due to diabetes-related comorbid conditions.³¹ In Ayurveda medicine, the treatment modalities focus on the whole-body system, expecting an impact on the quality of life of the patient,³³ and this study would provide the opportunity to assess the effect of these polyherbal Ayurvedic medicines on the QoL of affected patients.

Therefore, in this observational study conducted in an Ayurveda treatment setting, the safety and efficacy of LG in patients with T2DM, and its’ effect on the QoL of patients, were assessed.

Methods

Study Design, Setting, and Objectives

This was a prospective, observational study conducted at an Ayurveda clinic situated in the Western Province of Sri Lanka, which has been registered with the Department of Ayurveda, Ministry of Health, Sri Lanka. Ethics approval for the study was granted by the Ethics Review Committee of the Sri Lanka Medical Association (ERC/11-007). Written informed consent was obtained from all participants before enrolling them into the study. The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice. As this study was an observational study, it was excluded from the registration as a clinical trial in the Sri Lanka Clinical Trials Registry (SLCTR).

Study Population

Sixty newly diagnosed diabetic patients attending an Ayurveda clinic for treatment of T2DM who fulfilled the following inclusion and exclusion criteria and provided informed written consent were included in the study. Patients aged between 35 and 65 years and whose pre-treatment fasting blood glucose levels were within the range of 110–160 mg/dl and not using any allopathic medications were selected for the observation study, as it is common practice for diabetic patients to use both allopathic and traditional medications simultaneously. Patients who had diabetes-related complications such as foot ulcers, amputations, retinopathy, neurological deficits, and significant cerebrovascular, cardiac, renal, hepatic, or lung disease were excluded from the study. All selected participants were advised not to use any allopathic medications, over-the-counter antidiabetic medications or herbal supplements during the 24-week study period.

Study Schedule

All selected participants received counselling on adherence to healthy lifestyle behaviour, including the avoidance of smoking and alcohol, having a balanced diet, and regular physical exercise, as per the usual protocol used in diabetes treatment clinics. They were advised on the symptoms of hypoglycemia and requested to report any unusual symptoms or effects that may occur during the follow-up study period as per usual practice.

Sociodemographic data and the results of baseline laboratory investigations were recorded prior to commencing the prescribed herbal medication for these new clinic attendees. These included data on age, sex, body height and weight, relevant past medical history, FBG, HBA1c, serum creatinine, full blood count, lipid profile, and liver function tests. All patients underwent a microfilament examination of their feet and screening of their eyes to exclude sensory neuropathy and retinopathy prior to being included in the observational study to exclude any diabetes related complications.

A validated 15-item diabetes QoL brief clinical inventory developed by Burroughs and colleagues was used for evaluating the QoL of participants.³⁴ The responses to the questions were made on a Likert scale ranging from 1 (very satisfied) to 5 (very unsatisfied). It was translated into native languages, Sinhala and Tamil, and completed by patients before commencing treatment, and again at two-week intervals during the 24-week period of treatment. The suitability and comprehensibility of the translated versions of the inventory were evaluated by two healthcare professionals, as there were no validated language-specific instruments available for use. The selected patients were reviewed clinically at two-week intervals instead of the usual 4-week interval used by the clinic.

Fasting blood glucose (FBG) and post-prandial blood glucose (PPBG) were tested every four weeks. Glycosylated hemoglobin (HbA1c), serum creatinine, full blood counts, and liver function were tested at 12 weeks and 24 weeks.

Description of the Investigational Medication

Link Gluconorm (LG), a solid-form polyherbal formulation prescribed for the treatment of T2DM by Ayurveda practitioners, comprises a proprietary blend of seven medicinal herbs namely, the stem of Salacia reticulata Wight, the corm of Musa paradisiaca L., the whole plant of Sida rhombifolia subsp. alnifolia (L.) Ugbor., the whole plant of Tribulus terrestris L., the fruit of Phyllanthus emblica L., the heartwood of Santalum album L., and the whole plant of Coccinia grandis (L.) Voigt. It had been converted from a decoction to a solid dosage form to improve compliance. The solid form was prepared by using the aqueous alcoholic extract of the above components of medicinal plants while maintaining the proportions of medicinal plant ingredients used in the Ayurvedic preparation for the treatment of diabetes. Each tablet was standardized to contain 450 mg (± 5%) of the proprietary blend of the above plants. It was quality controlled according to qualitative and quantitative tests recommended for tablet dosage forms and by high-performance liquid chromatography (HPLC) (1260 Agilent Infinity HPLC System, USA) (Supplementary file 1). LG is prescribed as two tablets in the morning and afternoon and three tablets at night immediately prior to meals. The dosing of LG was based on the traditional dose of the polyherbal decoction recommended for diabetes.^15,35

Data Analysis

Data analysis was done using SPSS version 20 (SPSS Inc., Chicago, IL, USA). The data are presented as means, standard deviations (SD), and percentages. A paired t test was performed to ascertain whether significant differences existed between the biochemical tests of the subjects before and after the treatment. The changes over time in QoL were assessed using trend analysis graphs and 95% confidence intervals. A two-tailed P value of less than 0.05 was considered statistically significant. There were a few missing values for some parameters in the follow-up investigations (<8%). In such cases, the average values were used in computations. Since this is an observational study of a cohort of patients and not a comparative clinical trial, power calculations were not done for sample size determination.

Results

Baseline Characteristics of Participants

Of the 60 patients who were initially included in the study based on inclusion criteria, only 37 could be followed for the total period of 24 weeks. Others had to be excluded from the study as they were either lost for follow up (8 patients) or moved to allopathic medication clinics (15 patients) due to a variety of reasons not related to any adverse events of the medication. The baseline anthropometric and demographic characteristics of the 37 patients who completed the 24-week follow-up are summarized in Table 1.

Table 1.

Profile of Subjects at Baseline (n = 37).

Variables	Number / Mean ± SD*
Age (years)	48 ± 9
Sex	Female: 25 Male:12
Engaging in regular physical exercise	5
Body mass index /(kg/m²)	Female: 25.0 ± 4.4 Male: 25.2 ± 4.2
Fasting blood glucose (FBG) [mg/dL]	153.9 ± 15.6
Postprandial blood glucose PPBG [mg/dL]	191.3 ± 21.4
Hemoglobin [g/dL]	13.5 ± 0.5
Total cholesterol (mg/ dL)	207.2 ± 35.0
High density lipoprotein (mg/ dL)	57.5 ± 22.6
Low density lipoprotein (mg/ dL)	120.4 ± 30.9
Triglyceride (mg/ dL)	156.7 ± 57.6

*SD: Standard deviation.

Effects on Glycemic Parameters

Significant reductions in the mean values of fasting blood glucose [FBG] (153.85 mg/dL ± 15.62 to 129.01 mg/dL ± 12.88, t _paired = 2.95, p = 0.006), postprandial blood glucose [PPBG] (191.27 mg/dL ± 21.40 to 140.72 mg/dL ± 8.92, t _paired = 4.45, p < 0.001), and glycosylated hemoglobin [HbA1c] (8.51% ± 0.44 to 7.43% ± 0.4, t _paired = 5.59, p < 0.001) were observed from the baseline to the end of the study period (Table 2).

Table 2.

Changes in the Mean Glycemic Control Parameters Over the Study Period.

Variables	Mean ± SD*	Paired t-test value	p value**
Fasting Blood Glucose (mg/dL)
Baseline	153.85 ± 15.62
4^th week	144.44 ± 7.96	1.194	0.240
8^th week	145.99 ± 7.79	1.030	0.310
12^th week	139.73 ± 8.19	1.504	0.141
16^th week	131.08 ± 6.00	2.947	0.006
20^th week	130.43 ± 6.37	2.762	0.009
24^th week	129.01 ± 6.44	2.950	0.006
Post-prandial blood glucose (mg/dL)
Baseline	191.27 ± 21.40
4^th week	183.31 ± 13.23	0.838	0.408
8^th week	176.84 ± 10.13	1.481	0.147
12^th week	173.12 ± 8.73	1.674	0.103
16^th week	157.03 ± 8.79	3.322	0.002
20^th week	140.72 ± 4.47	4.451	<0.001
Glycosylated hemoglobin (%)
Baseline	8.52 ± 0.22
12^th week	7.77 ± 0.24	3.559	0.001
24^th week	7.43 ± 0.20	5.590	<0.001

*SD: Standard deviation, **p-values were calculated for reduction of biochemical parameters from baseline. Normal ranges: FBG, 70 mg/dL - 100 mg/dL; PPBG, < 140 mg/dL; HbA1c, 4%—5.6%.

Effect on Quality of Life

In the 15-item diabetes QoL brief clinical inventory used in this study, the scores are inversely related to QoL (the higher the scores, the lower the QoL). The QoL showed an improving trend over the study period of 24 weeks. There was a significant difference in the mean QoL scores at baseline and 24 weeks (1.93 ± 0.22 to 1.55 ± 0.08, t _paired = 3.59, p < 0.01), indicating a significant increase in the QoL of the patients who were treated with LG over a period of 24 weeks (Figure 1).

Figure 1.

Changes in the Mean Score of Quality of Life (QoL) Over the Trial Period.

Effect on Safety-Related Biomarkers and Adverse Events

None of the participants reported any adverse events during the study period. None complained of symptoms of hypoglycemia such as dizziness, sweating, confusion, etc. There were no significant changes in mean values from baseline to the end of the study period in biomarkers, used for assessing safety in relation to hematology, liver, renal parameters (Table 3). The mean serum ALT level showed a significant reduction from the mean baseline level (33.85 IU/L ± 6.4 to 29.07 IU/L ± 4.02, t _paired = 2.18, p < 0.05) but remained within the normal range at 24 weeks. Certain lipid profile markers such as total cholesterol and low density lipoproteins improved significantly (Table 3).

Table 3.

Changes in Mean Hematological and Biochemical Parameters at Baseline and at 24 Weeks.

Variables	Baseline Mean value (SD)*	After 24 weeks Mean value (SD)*	Paired t-test value	p value**
Serum glutamic pyruvic transaminase (SGPT) (IU/L)	33.85 ± 6.4	29.07 ± 4.02	2.18	0.03
Serum glutamic-oxaloacetic transaminase (SGOT) (IU/L)	26.23 ± 6.0	24.81 ± 4.6	1.03	0.31
Alkaline phosphatase (IU/L)	175.4 ± 17.4	169.16 ± 16.0	1.38	0.17
Gamma-glutamyl transferase (GGT) (IU/L)	63.92 ± 57.2	51.2 ± 29.3	0.87	0.38
Total bilirubin (mg/dL)	0.62 ± 0.06	0.59 ± 0.06	−0.92	0.36
Total protein (g/L)	74.03 ± 1.36	74.17 ± 1.16	−0.21	0.83
Serum creatinine (mg/dL)	0.91 ± 0.04	0.91 ± 0.04	−0.028	0.91
White blood cell count (WBC) (10⁹/L)	8.73 ± 0.64	8.27 ± 0.54	1.72	0.09
Red blood cell count (RBC) (10¹²/L)	4.88 ± 0.16	4.84 ± 0.14	0.71	0.48
Platelet count (10⁹/L)	284.6 ± 17.2	285.2 ± 17.0	−0.08	0.93
Hemoglobin / (g/dL)	13.5 ± 0.54	13.6 ± 0.54	−0.59	0.55
Total cholesterol (mg/dL)	207.2 ± 35.0	192.9 ± 35.6	2.208	0.03
Triglyceride (mg/dL)	156.7 ± 57.6	148.1 ± 65.5	0.948	0.35
High density lipoprotein (mg/dL)	57.5 ± 22.6	53.5 ± 6.3	1.148	0.26
Low density lipoprotein (mg/dL)	120.4 ± 30.9	106.7 ± 31.5	2.46	0.02

*SD: Standard deviation, **p-values were calculated for changes in biochemical and haematological parameters from baseline.

Discussion

T2DM is a highly prevalent global health problem, and glycemic control is the mainstay of treatment to prevent or minimize complications. The occurrence of physical disabilities following complications, treatment costs, and other socio-economic consequences such as loss of employment due to disabilities affects the health-related QoL of patients.^30,32 The key goals of care are to prevent complications and related disabilities, which in turn would improve the QoL of affected patients, which could be achieved through consistent glycemic control.

Herbal medicines for diabetes are gaining popularity among patients due to the common belief that they have fewer side effects due to their connectivity to nature.³⁶ A considerable number of in vivo, in vitro, and clinical studies on the efficacy of herbal treatments in controlling diabetes have been conducted and published previously.^37,38 A randomized placebo-controlled study conducted to evaluate a traditional polyherbal formulation administered for 3 months in 150 patients with T2DM showed that the herbal formulation was as effective as a daily dose of 1000 mg of metformin in statistically significantly reducing FBG and HbA1c. No notable hepatic, renal and gastrointestinal side effects were observed in the trial groups.³⁹ Another randomized, double-blind clinical trial that evaluated the efficacy of a proprietary herbal formulation, GlycaCare-11, as monotherapy in pre diabetic (n = 29) and newly diagnosed T2DM (n = 40) patients administered orally over 120 days showed statistically significant reductions in FBG and HbA1c and had similar efficacy rates to metformin.⁴⁰ A randomized, single-blind, placebo-controlled trial carried out as an add-on polyherbal formulation on 92 T2DM patients who were receiving oral hypoglycaemic drugs showed statistically significantly reductions in FBG, PPBG and HbA1c in the absence of significant adverse effects.⁴¹

The results have been reasonably consistent, and there is a great need to continue controlled clinical trials on such medications. Traditional or Ayurvedic herbal recipes have been used for controlling diabetes, and some recipes have been commercialized as over-the-counter herbal supplements for diabetes.³⁶ However, the clinical efficacy of most of those supplements has not been validated using RCTs. Hence, the evaluation of the efficacy of these herbal medicines, both prescribed and over-the-counter products, using clinical studies is of paramount importance for ensuring the welfare of patients.

Significance of Results

In this study, we assessed the efficacy and safety of the polyherbal formulation, LG, in the treatment of uncomplicated T2DM in a group of patients treated at an Ayurvedic clinic in Sri Lanka. 37 newly diagnosed uncomplicated diabetic patients who were treated solely with LG were followed up for a period of 24 weeks, and their disease monitoring biomarkers, safety parameters, and QoL were assessed.

With regard to safety, there were no episodes of hypoglycemia or adverse changes in the mean levels of liver, kidney, and hematological parameters, indicating the safety of the medication. There were significant reductions in their mean PPBG, FBG, and HbA1c levels at the end of the 24-week study period. PPBG and FBG showed a significant reduction even at 16 weeks of treatment. HbA1c showed a significant reduction as early as 12 weeks, and the reduction was highly significant. As these parameters failed to reach pre-diabetic or diabetes control levels at the end of 24 weeks, a longer duration of follow-up may be needed in future studies. Significant lowering of total cholesterol and low-density lipoproteins at the end of 24 weeks were additional positive findings in these patients, which indicates beneficial effects on metabolic parameters.

There was a significant change in the mean QoL score between the baseline and at the end of the 24- week study, indicating significant improvement in the QoL of patients who participated. No adverse events were either reported or observed over the study period. Hence, the results indicate that the daily use of LG is safe and significantly improves health-related quality of life in patients with diabetes.

Ayurveda practitioners use polyherbal decoctions for many diseases. LG has been formulated using seven medicinal herbs commonly used by Ayurvedic practitioners for the treatment of diabetes.^15,30 The efficacy and safety of this preparation have been further substantiated by this preliminary clinical study.

The previous reports of laboratory and clinical studies done on medicinal plants that comprise LG, show very encouraging results, as described above. The use of a combination of plants in the form of decoctions is an important concept in Ayurveda, as it is believed that the synergistic effects of plant combinations may enhance therapeutic effects and decrease toxicity. LG tablets have been prepared to simulate the actual Ayurveda practice of treating diabetes. The solid forms of these decoctions are likely to increase compliance compared to traditional decoctions due to the ease of consumption and improved palatability.

Limitations of the Study

Only a small number of patients could be included in the study, as only a few used LG alone for 24 weeks, as most resorted to using traditional medicines as an add-on therapy with allopathic medicines due to a variety of reasons. The relatively short duration of follow-up, the unblinded nature of the study, and the lack of a parallel treatment arm or control arm were the other limitations which require addressing in future studies.

Implications for Future Research

This preliminary study, which confirms the safety of this medication, will pave the way for designing RCTs in a larger group of patients to study both the efficacy and safety of this medication further. It is common practice for patients to use over-the-counter herbal preparations or prescribed traditional medicines as add-on therapy for many chronic illnesses. Therefore, it is best that future RCTs are designed to reflect these practices rather than stand-alone medicines, as this will bring out any issues related to drug interactions and safety. It is also important to assess the safety of long-term use of LG on hematology, liver, and renal profiles using double blinded placebo controlled RCTs prior to recommending them as an add-on therapy for the treatment of T2DM.

Conclusions

Complementary and alternative medicine practitioners have been using herbal treatment to treat diabetes for many centuries. There is an urgent need to investigate the efficacy and safety of these traditional remedies using scientific methodology and specifically RCTs. Our results indicate that the polyherbal product LG is effective in significantly improving glycemic indices, and the QoL of diabetic patients. LG had additional positive effects on metabolic indices through lipid-lowering functions. Further, no significant changes were observed in laboratory-based safety indices and the product appears to be safe. Our study emphasizes the need for double-blind RCTs to investigate the efficacy of LG in treating T2DM with a longer duration of follow-up. In studies that may plan to use LG as supplementary medication, the herbal and allopathic drug interactions need to be investigated, as many patients in Asia tend to use combinations of herbal products with established allopathic anti-diabetic medications.

Supplemental Material

sj-docx-1-chp-10.1177_2515690X251347167 - Supplemental material for Efficacy and Safety of an Ayurveda Herbal Formulation in Uncomplicated Type 2 Diabetes mellitus

Supplemental material, sj-docx-1-chp-10.1177_2515690X251347167 for Efficacy and Safety of an Ayurveda Herbal Formulation in Uncomplicated Type 2 Diabetes mellitus by Bilesha Perera, Colvin Goonaratna, Hettiarchchige Ariyawansa, Nirmala Senaratna and Jennifer Perera in Journal of Evidence-Based Integrative Medicine

Footnotes

Abbreviations

CRediT Authorship Contribution Statement

Bilesha Perera: Methodology, Formal analysis, Data curation, Writing- Initial draft.

Colvin Goonaratna: Conceptualization, Methodology, Supervision, Review & editing.

Hettiarachchige Ariyawansa: Conceptualization, Methodology, Supervision, Investigation Nirmala Senaratna: Patient recruitment, Investigation.

Jennifer Perera: Writing the draft paper, Data curation, Methodology, Review & editing.

Data Availability Statement

The data supporting the study findings are included within the manuscript. The raw datasets used during the current study are available from the corresponding author upon request.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Considerations

Ethics approval to conduct the study was received from the Ethics Review Committee of the Sri Lanka Medical Association (ERC/11-007). Informed written consent was obtained from volunteer patients prior to participating in the study. The study did not require registration in the Sri Lanka Clinical Trials Registry which is a primary Register of the WHO clinical trials Registry, as it was not a clinical trial, but an observational study. Animal studies were not conducted during this study.

Funding

The authors disclosed receipt of the following financial support for conducting the research and publication of the article. This study was financially supported by Research & Development Centre of Link Natural Products (Pvt.) Limited, Sri Lanka. The sponsor did not participate in the design of study, in the collection, analysis and interpretation of data, in the writing of report and in the decision to submit the article for publication.

Research and Development Centre, Link Natural Products Pvt Limited, Sri Lanka, (grant number Nil).

ORCID iDs

Jennifer Perera

Nirmala Senaratna

Bilesha Perera

Supplemental Material

Supplemental material for this article is available online.

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