E-ISSN:2456-3110

Research Article

Diabetes Mellitus

Journal of Ayurveda and Integrated Medical Sciences

2022 Volume 7 Number 11 December
Publisherwww.maharshicharaka.in

Therapeutic trial of an Ayurvedic compound in Madhumeha (Diabetes Mellitus)

Bhardwaj A.1*, Kumar Sharma D.2
DOI: http://dx.doi.org/10.21760/jaims.7.11.3

1* Anita Bhardwaj, Associate Professor, Dept. of Kriya Sharira, Rajkiya Ayurvedic, Yoga avam Prakritik Mahavidhyalaya, Jaipur, Rajasthan, India.

2 Deepak Kumar Sharma, Chief Medical Officer, Ayurveda, ESIC Model Hospital, Jaipur, Rajasthan, India.

Diabetes mellitus has been emerged as one of the major health problems, which is found commonly all over the world. In Ayurveda, inclusion of Madhumeha, in eight major diseases (Ashthamahagada) indicates the gravity and significant attributed to it. In this study a comparative trial between an Ayurvedic compound (Kalpit) named as Madhudaman Yoga, and Glipizide as control drug was carried out. 50 patients of Diabetes mellitus were registered from the OPD and IPD of NIA, Jaipur for this study. These patients were divided into two groups. Group A (control drug) – 25 patients took Glipizide 5 mg twice daily for 75 days. Group B (trial drug) - 25 patients took 2 capsules of Madhudaman Yoga 500 mg, twice daily for 75 days. At the end of the study it was observed that the trial drug showed significant improvement in FBS, PPBS, and HbA1c (p<0.001). Significant relieves in many symptoms were also observed. The overall effect of Madhudaman Yoga was approximately similar to that of the control drug. No side effects were noticed in any of the patients of the trial group.

Keywords: Madhumeha, Diabetes mellitus, Madhudaman yoga, Glipizide

Corresponding Author How to Cite this Article To Browse
Anita Bhardwaj, Associate Professor, Dept. of Kriya Sharira, Rajkiya Ayurvedic, Yoga avam Prakritik Mahavidhyalaya, Jaipur, Rajasthan, India.
Email: 		Anita Bhardwaj, Deepak Kumar Sharma, Therapeutic trial of an Ayurvedic compound in Madhumeha (Diabetes Mellitus). J Ayu Int Med Sci. 2022;7(11):14-21.
Available From
https://www.jaims.in/jaims/article/view/2161

Manuscript Received Review Round 1 Review Round 2 Review Round 3 Accepted
2022-11-01 2022-11-03 2022-11-10 2022-11-17 2022-11-24
Conflict of Interest Funding Ethical Approval Plagiarism X-checker Note
Nil Nil Yes 18%

© 2022by Anita Bhardwaj, Deepak Kumar Sharmaand Published by Maharshi Charaka Ayurveda Organization. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ unported [CC BY 4.0].

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Introduction

Diabetes mellitus has been classified among one of the major health problems, which is found commonly in socio-economically improved societies all over the world.

According to WHO about 422 million people worldwide have diabetes, the majority living in low and middle income countries, and 1.5 million death are directly attributed to diabetes each year. Both the number of cases and the prevalence of diabetes have been steadily increasing over the past few decades.[1] With an increasing incidence worldwide, DM will be a leading cause of morbidity and mortality for the foreseeable future.[2]

The disease Madhumeha is described in almost all available texts of Ayurveda under the sub type of Vataja Prameha. Its inclusion in eight major disease (Asthamahagada) indicates the gravity and significant attributed to it.[3,4] Acharya Charaka has described the character of excrete urine like pale in appearance, Kashaya and Madhura in taste and warm and Ruksha in Guna.[5] Prabhuta Mutrata (excessive urination) and Avila Mutrata (turbid, unclear appearance) are general cardinal symptoms of Prameha.[6] Vata is provoked due to Dhatu Kshaya both Gambhira and Sarabhoot. The provoked Vata vitiates Oja and excrete by Basti and leads to Madhumeha.[7]

Non enzymatic Glycosylation and Intercellular Hyperglycemia with disturbances in Polyol pathways are two metabolic events appear to be involved in the genesis of the genesis of complication of diabetes.[8]

Ayurveda is the ray of hope, which can contribute in this regard. Diabetes mellitus can be correlated to 'Madhumeha' because they have similarities in etiology, pathogenesis, symptomatology, complications etc. Keeping in view the developing interest in therapeutic diabetology, the realization of the need to analyze Madhumeha from the therapeutic standpoint has emerged. There is no satisfactory treatment available in modern system of medicine for this disease. Therefore, it was decided to evaluate certain Ayurvedic drugs which could be safe, effective economical, easily available having no side effects. For this purpose, an Ayurvedic formulation (Madhudaman Yoga) was selected as trial drug.

Materials and Methods

This study was conducted under a strict protocol to prevent bias and to reduce the sources of error in the study. This control trial study was conducted under the following steps:-
1. Selection of patients

2. Administration of Drug

3. Follow up study

4. Assessment of progress

Selection of patients: A written information and consent letter had been given to patients. The patients were explained about the purpose, procedures and possible dangers of the trial.

The patients for this study were selected from OPD and IPD of NIA hospital, Jaipur after screening them as per Ayurvedic and modern criteria for Madhumeha. Total 50 patients were registered for the study.

Criteria for the selection of the patient
A. Inclusion criteria

1. Patients in the age group between 20 to 80 years.

2. Diagnosed cases of Diabetes mellitusB.

B. Exclusion criteria

1. Patients of age less the 20 yrs and above 80 years.

2. Pregnant woman.

3. Patients with serious disorders like MI, CHF, cirrhosis of liver, severe complicated DM etc.

4. Patients taking drugs like corticosteroids, tricycle antidepressant, cycloheptadine which leads to weight gain.

Diagnostic Criteria: The criteria were developed to select the cases on clinical ground. Which is based on the signs and symptoms, described in Ayurvedic and modern texts and lab investigations.

The following laboratory criteria were used on investigation ground:

  • Haematological - Hb%, TLC, DLC, ESR
  • Biochemistry - FBS, PPBS, Lipid Profile
  • Urine Examination - Routine & microscopic
  • Specific Test - HbA1C

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Administration of drug: For this trial two drugs Madhudaman Yoga and Glipizide were selected. Each 500 mg capsule of Madhudaman Yoga consists of 250 mg of Suddha Shilajita and 250 mg Ghana Satva of seven drugs - Puga, Khadira, Paneer Phala, Guduchi, Nimba, Tulsi, Haritaki. This drug was prepared by classical methods in Pharmacy of N.I.A. Jaipur.

Fifty (50) selected patients of Madhumeha were divided into 2 groups for the drug administration as follows:

a. Control Group (Group A) : In this group 25 clinically and pathologically diagnosed patients of Madhumeha were registered. these patients were recommended one table Glipizide 5 mg twice daily, with the water before meal as allopathic drug, for 75 days.

b. Madhudaman Yoga - Kalpit (Group-B) : In this group 25 diagnosed patients of Madhumeha were registered. These were recommended Madhudaman Yoga (Kalpit) in the dose of 500mg two capsule twice daily with lukewarm water, for 75 days.

Follow Up Study

  • Patients were followed up after every 25 days.
  • Laboratory investigation was repeated after completion of trial
  • Improvement and any side effects were noted down.

Assessment of progress: The assessment of progress was made by the observations and examination of patients. Subjective & objective parameters were decided for the clinical assessment.

Subjective Parameters

  • Sign and symptoms of Diabetes mellitus
  • Sign and symptoms of Madhumeha
  • Purvaroopa of Prameha
  • Dashavidha Pariksha
  • Upadrava of Prameha

for the subjective assessment, different symptoms were graded as follows:

Symptoms Grade

  • Absent 0
  • Mild 1
  • Moderate 2
  • Severe 3
  • Very severe 4

These parameters were those, which a physician cannot be measure

In this study following parameters used.

1. Prabhoot Mootrata (Polyurea)

2. Aavil Mootrata (Turbidity in urine)

3. Pipasa Adhikya (Polydipsia)

4. Kshuda Adhikya (Polyphagia)

5. Swedatipravriti (Excessive sweating)

6. Daurbalya (Weakness)

7. Atinidra (Excessive Sleep)

8. Kandu (Itching)

9. Mukhmadhuraya (Sweetness of mouth)

10. Hast Pada Daha (Burning sensation in hands of feet)

11. Mukh Talu Shosha (Dryness of mouth)

12. Malavritta Jihwa (Coated tongue)

13. Drishti Daurbalyata (Blurry vision)

14. Tingling or numbness in hands or feet

15. Frequent infections

16. Delayed wound healing

Objective Parameters: The following parameters were assessed objectively

  • Weight
  • BMI
  • Waist circumference
  • Hip circumference
  • Skin fold thickness

All investigations done on Patients in Rog Nidana evam Vikriti Vigyan Lab. NIA, Jaipur.

Result and Discussion

All the 50 patients of Diabetes mellitus registered and completed their trial were assessed for the subjective, objective, and investigational changes, if any after the study.


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It was observed that there was a considerable improvement in feeling of wellbeing in all the patients of both groups after the course.

Subjective Assessment: While assessing the clinical improvement after the administration of tab. Glipizide 5 mg twice daily in group- A and after administration of Madhudaman Yoga 2 capsules (500 mg each) twice daily in group B. The following statistical results were found according to wilcoxon matched pairs signed-rank test.

Wilcoxon matched-pairs signed-ranks test for Subjective Assessment

T+ = Sum of positive ranks

T- = Sum of negative ranks

W = Sum of all signed rank

P = Two tailed 'p' value

Table 1: Improvement in Prabhoota Mootrata

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.80 0.88 0.92 0.812 0.162 190 0 190 <0.0001
B 1.16 0.56 0.60 0.645 0.129 91 0 91 0.0002

Table 2: Improvement in Avila Mootrata

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.56 0.96 0.60 0.707 0.141 78 0 78 0.0005
B 1.40 0.88 0.52 0.7141 0.143 85 6 79 0.0034

Table 3: Improvement in Pipasadhikya

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.56 0.80 0.76 0.779 0.156 146 7 139 0.0003
B 1.24 0.68 0.56 0.820 0.164 55 0 55 0.0020

Table 4: Improvement in Kshudhadhikya

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.36 0.64 0.72 1.021 0.204 150 21 129 0.0034
B 0.79 0.56 0.23 0.779 0.159 21 7 14 0.2969

Table 5: Improvement in Swedatipravritti

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.36 0.72 0.64 0.568 0.114 161.5 9.5 152 0.0003
B 1.00 0.60 0.40 0.764 0.153 67 11 56 0.0269

Table 6: Improvement in Daurbalyata

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.44 0.72 0.72 0.614 0.123 136 0 136 <0.0001
B 1.60 0.76 0.84 0.943 0.189 130.5 5.5 125 0.0003

Table 7: Improvement in Atinidra

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 0.96 0.44 0.52 0.963 0.192 51 4 47 0.0137
B 1.36 0.84 0.52 0.770 0.154 106 14 92 0.0067

Table 8: Improvement in Kandu

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.52 0.68 0.84 0.624 0.125 171 0 171 <0.0001
B 0.52 028 0.24 0.523 0.105 31.5 4.5 27 0.0547

Table 9: Improvement in Mukhamadhurya

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.28 0.60 0.68 0.627 0.125 162 9 153 0.0003
B 1.24 0.84 0.40 0.816 0.163 57 9 48 0.0322

Table 10: Improvement in Hast-Pada Daha

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 0.92 0.36 0.56 0.583 0.116 91 0 91 0.0002
B 0.96 0.52 0.44 0.583 0.116 84 7 77 0.0046

Table 11: Improvement in Mukh-Talu Shosha

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.68 0.96 0.72 0.678 0.135 162.5 8.5 154 0.0002
B 1.64 0.80 0.84 1.068 0.213 114.5 5.5 109 0.0006

Table 12: Improvement in Malavritta Jihwa

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.68 0.96 0.72 0.737 0.147 120 0 120 <0.0001
B 1.56 1.04 0.52 0.653 0.130 66 0 66 0.001

Table 13: Improvement in Drishti Daurbalayata

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 0.68 0.20 0.48 0.586 0.117 97.5 7.5 90 0.0023
B 1.00 0.76 0.24 0.436 0.087 21 0 21 0.0313

Table 14: Improvement in Tingling and Numbness

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 0.68 0.48 0.20 0.50 0.10 24 4 20 0.1094
B 0.80 0.60 0.20 0.50 0.10 24 4 20 0.1094

Table 15: Improvement in Frequent infections

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.76 0.96 0.80 0.866 0.173 175 15 160 0.0005
B 0.72 0.40 0.32 0.476 0.095 36 0 36 0.0078

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Table 16: Improvement in delayed wound healing

Group Mean Mean diff. SD Diff SE Diff T+ T- W 'p' value
BT AT
A 1.04 0.68 0.36 0.490 0.098 45 0 45 0.0039
B 1.00 0.56 0.44 0.583 0.116 55 0 55 0.0020

Group A: Extremely significant improvement was noticed in Prabhoota Mootrata (p<0.0001), Avila Mootrata (p=0.0005), Pipasadhikya (p=0.0003), Swedatipravritti (p=0.0003), Daurbalyata (p<0.0001), Kandu (p<0.0001), Mukh Madhurya (p=0.0003), Hast-Pada Daha (p=0.0002), Mukh-Talu Shosha (p=0.0002), Malavritta Jihwa (p<0.0001) and in frequent infections (p=0.0005).

Statistically very significant improvement was noticed in Kshudhadhikya (p=0.0034), Drishti Daurbalyata (p=0.0023) and delayed wound healing (p=0.0039).

Significant improvement was noticed in Atinidra (p=0.0137).

Improvement in tingling or numbness in hands and feet was considered not significant statistically (p=0.1094).

Group B: Extremely significant improvement was noticed in Prabhoota Mootrata (p=0.0002), Daurbalyata (P=0.0003) and Malavritta Jihwa (p=0.001) and Mukh-Tatu Shosha (p=0.0006).

Statistically very significant improvement was noticed in Avila Mootrata (p=0.0034), Pipasadhikya (p=0.002), Atinidra (p=0.0067), Hast-Pada Daha (p=0.0046), frequent infections (p=0.0078) and delayed wound healing (p=0.002).

Significant improvement was noticed in Swedatipravritti (p=0.0269), Mukhmadhuryata (p=0.0322) and Drishti Darubalyata (p=0.0322) and Drishti Daurbalyata (p=0.0313).

Statistically not quite significant improvement was noticed in Kandu (p=0.0547) and insignificant improvement in Kshudhadhikya (p=0.2969) and tingling or numbness in hands or feet (p=0.1094).

Objective Assessment

Body weight, Body mass index, waist circumference, hip circumference and skin fold thickness parameters were used for the objective assessment.


Objective improvement in Group - A

Objective parameter Mean Dif. % of Change SD SE 't' 'p'
BT AT
Weight 68.76 68.01 0.75 1.09 0.82 0.16 4.58 <0.001
BMI 26.02 25.72 0.30 1.14 0.32 0.06 4.67 <0.001
Waist Circumference 32.50 32.14 0.36 1.10 0.41 0.08 4.37 <0.001
Hip Circumference 35.16 34.80 0.36 1.04 0.55 0.11 3.31 <0.01
Skin fold thickness 18.28 18.04 0.24 1.33 0.30 0.06 4.05 <0.001

Objective improvement in Group - B

Objective parameter Mean Dif. % of Change SD SE 't' 'p'
BT AT
Weight 67.16 66.14 1.02 1.52 0.80 0.16 6.40 <0.001
BMI 24.98 24.59 0.39 1.55 0.30 0.06 6.40 <0.001
Waist Circumference 31.56 30.67 0.88 2.80 0.95 0.19 4.65 <0.001
Hip Circumference 36.15 35.92 0.23 0.63 0.22 0.04 5.25 <0.001
Skin fold thickness 16.01 15.68 0.33 2.05 0.37 0.07 4.42 <0.001

Group – A: Improvement in weight (p<0.001), BMI (p<0.001), waist circumference (p<0.001) and skin fold thickness (p<0.001) is statistically highly significant.

Significant improvement was observed in Hip circumference (p<0.01).

Group – B: Statistically highly significant improvement was considered in weight (p<0.001), BMI (p<0.001), waist circumference (p<0.001), Hip circumference (p<0.001) and skin fold thickness (p<0.001). These data shows that Madhudaman Yoga is also an effective drug for obese diabetes patients.

Changes in Hematological Investigation in Group - A

Investigation Mean Dif. % of Change SD SE 't' 'p'
BT AT
Hb 12.91 12.77 0.14 1.06 0.92 0.18 0.74 >0.1
TLC 7532.80 7652.00 119.20 1.58 1120.61 224.12 0.53 >0.1
DLC-N 62.76 62.44 0.32 0.51 4.27 0.85 0.37 >0.1
DLC -L 32.80 32.52 0.28 0.85 4.83 0.97 0.29 >0.1
DLC -E 2.60 2.68 0.08 3.08 1.29 0.26 0.31 >0.1
DLC -M 2.08 2.40 0.32 15.38 1.25 0.25 1.28 >0.1
ESR 18.88 19.80 0.92 4.87 2.98 0.60 1.54 >0.1

Changes in Hematological Investigation in Group-B

Investigations Mean Dif. % of Change SD SE T P
BT AT
Hb 13.32 12.74 0.58 4.33 1.56 0.31 1.84 <0.1
TLC 7402.00 7192.00 210.00 2.84 1161.72 232.34 0.90 >0.1
DLC-N 62.00 62.44 0.44 0.71 4.85 0.97 0.45 >0.1
DLC -L 32.76 33.20 0.44 1.34 3.73 0.75 0.59 >0.1
DLC -E 2.48 2.48 0.00 0.00 1.55 0.31 0.00 -
DLC -M 2.72 2.12 0.60 22.06 1.68 0.34 1.78 <0.1
ESR 19.84 23.52 3.68 18.55 7.39 1.48 2.49 0.02

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Changes in Biochemical and HbA1C & Urine Investigation in Group – A

Investigations Mean Dif. % of Change SD SE T P
BT AT
FBS 148.21 119.63 28.58 19.28 14.25 2.85 10.03 <0.001
PPBS 216.56 163.15 53.41 24.66 29.28 5.86 9.12 <0.001
HbA1C 9.10 7.45 1.65 18.12 1.15 0.23 7.16 <0.001
Cholesterol 197.91 197.04 0.87 0.44 14.75 2.95 0.29 >0.1
Tg 138.35 135.85 2.50 1.81 9.84 1.97 1.27 >0.1
HDL 46.52 47.00 0.48 1.02 2.78 0.56 0.86 >0.1
LDL 123.72 122.88 0.85 0.69 15.48 3.10 0.27 >0.1
VLDL 27.67 27.16 0.50 1.82 1.97 0.39 1.28 >0.1
FUS 0.20 0.04 0.16 80.00 0.37 0.07 2.14 <0.05
PPUS 1.04 0.32 0.72 69.23 0.84 0.17 4.27 <0.001
U. Protein 0.32 0.28 0.04 12.50 0.45 0.09 0.44 >0.1

Changes in Biochemical and HbA1C & Urine Investigation in Group - B

Investigations Mean Dif. % of Change SD SE T P
BT AT
FBS 161.10 112.62 48.48 30.09 39.48 7.90 6.14 <0.001
PPBS 238.77 164.43 74.34 31.13 54.57 10.91 6.81 <0.001
HbA1C 8.10 6.80 1.29 15.96 1.26 0.25 5.12 <0.001
Cholesterol 198.53 179.50 19.03 9.58 34.87 6.97 2.73 <0.02
Tg 147.22 136.94 10.29 6.99 27.10 5.42 1.90 <0.1
HDL 47.75 52.17 4.42 9.25 8.51 1.70 2.60 <0.02
LDL 118.50 101.57 16.93 14.28 34.97 6.99 2.42 <0.05
VLDL 30.23 27.40 2.83 9.35 6.77 1.35 2.09 <0.05
FUS 0.36 0.04 0.32 88.89 0.69 0.14 2.32 <0.05
PPUS 1.04 0.40 0.64 61.54 0.70 0.14 4.57 <0.001
U. Protein 0.52 0.48 0.04 7.69 0.45 0.09 0.44 >0.1

Insignificant changes were observed in hematological investigations i.e., Hb (p>0.1), TLC (p>0.1), DLC (p>0.1), ESR (p>0.1) in Group A. But in Group B significant change in ESR was observed (p=0.02), rest hematological investigations Hb (p<0.1), TLC (p>0.1), DLC (p>0.1), like in Group A were insignificant.

Statistically highly significant improvement was observed in fasting Blood sugar, Post prandial Blood sugar, and HbA1C in both Groups (p<0.001).

The patients of Group-A showed insignificant improvement in the level of S. Cholesterol (p>0.1), S. Triglycerides (p>0.1), HDL (p>0.1). LDL (p>0.1) and VLDL (p>0.1).

In Group B, significant reduction was reported in the level of S. Cholesterol (p<0.02), LDL (p<0.05) and VLDL (p<0.05), significant

elevation in HDL (p<0.02) and insignificant reduction in S. Triglycerides (p<0.1) was reported in Group-B patients.

Statistically significant improvement was reported in fasting urine sugar level in Both groups (p<0.05). Highly significant reduction was reported in post prandial urine sugar level in Group-A and Group-B (p<0.001). Insignificant changes were found in urine protein in Both groups (p>0.1)

Discussion regarding effect of drug

Almost all ingredients of Madhudaman Yoga have been described in Ayurvedic Samhitas as parts of Anti Madhumeha Yogas. These all ingredients of Madhudaman Yoga, individually have the capacity to lower blood sugar but in Ghana Satva combination form, the results are tremendous, not only on controlling blood sugar but also dyslipidemia & obesity.

Most of the drugs contained in Madhudaman Yoga have properties like Vata-Kapha Shamak, Deepana, Rasayana, Pachan, Medohara, Shoshana. These are likely to break down the Samprapti of Madhumeha (DM).

This drug probably may increase insulin secretion from pancrease, decrease hepatic gluconeogenesis, increase glucose uptake in the periphery or decrease insulin resistance, further research is required to establish these mechanisms.

No any side effect was detected during the drug trial.

Conclusion

Significance of symptomatic relief in patients taking Madhudaman Yoga is just similar to the effect of the control drug, Glipizide. But no side effect of Madhudaman Yoga was observed in this trial. There is highly significant improvement in FBS, PPBS, HbA1C and PPUS in the patients who were treated with the trial drug.

Statistically significant results was observed in controlling dyslipidemia and this drug was found to be beneficial in weight reduction.

Reference

1. https://www.who.int/health-topics/diabetes year 2022


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2. Harrison’s principles of Internal medicine by Fauci, Braunwald 16th edition, pg 2152 Mchraw Hill Bool Company, New York.

3. Charak indriya sthana 9/8-page no. 1004, part 1 Charak Samhita, Chaukhamba Bharti Academy, Varanasi 2009

4. Sushruta samhita sutra 33/4, page no. 126, part1 Sushruta Samhita, Chaukhmba Sanskit Sanshthan, Varanriasi, thirteen edition, 2002

5. Charak nidana sthana 4/44 page no. 639, part 1 Charak Samhita, Chaukhamba Bharti Academy, Varanasi 2009

6. Sushruta samhita nidana 6/6, page no. 252, part1 Sushruta Samhita, Chaukhmba Sanskit Sanshthan, Varanriasi, thirteen edition, 2002

7. Charak chitisa sthana 6/11, page no. 233, part 2 charak samhita, chaukhamba bharti academy, Varanasi 2011

8. Robbins and Cotran Pathological basis of disease, 6th Edition, 2002, Elsevier, page no 919


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