(The Indian Practitioner, (1993): (XLVI), 12, 917-922)

Efficacy and Safety of Diabecon (D-400), A Herbal Formulation, in Diabetic Patients

V.H. Yajnik,

Professor H.K. Acharya, Asst. Professor M.P. Vithlani,

Resident. Department of Medicine, and

N.V. Yajnik, Resident. Department of Medicine,

M.P. Shah Medical College, Jamnagar, India.

SUMMARY Diabecon (D-400), a herbal formulation with hypoglycaemic effect, was studied for 12 weeks in 43 patients of maturity-onset diabetes. Diabecon (D-400) significantly reduced fasting (FBS) and two-hour postprandial blood sugar (PPBS) in newly diagnosed diabetics and in those already stabilised on antidiabetic medication. Oral hypoglycaemic agents could be omitted in 80% of cases, and the dosage could be reduced in the remaining, while maintaining equally good or better control of diabetes in patients already stabilised with these drugs. Insulin dosage could also be similarly reduced. Side-effects were absent. No deleterious effects were observed on the liver, kidney or haemopoietic functions. Diabecon (D-400) is a useful addition to the existing armamentarium of antidiabetic drugs. INTRODUCTION Many herbs have been shown to have hypoglycaemic action in animals and humans. However, none is accepted as a dependable antidiabetic drug. Careful formulation of herbal remedies is very essential. Diabecon (D-400), one such formulation, has been shown to bring about a moderate fall in blood sugar in a certain proportion of normal and alloxan-induced diabetic rats. Further, mere hypoglycaemic action may not be ideal for an antidiabetic drug. In experimental studies, Diabecon (D-400) has also been shown to prevent renal damage in alloxan-induced diabetic rats. We, therefore, attempted to evaluate the safety and efficacy of Diabecon (D-400) in maturity-onset diabetic patients. MATERIAL AND METHODS Patients of diabetes mellitus, of either sex and aged above 30 years, and who were not grossly obese (weight not more than 20% of the average) were included. Newly diagnosed patients as well as patients stabilised on oral hypoglycaemic agents (OHA) or on insulin were also included. Patients with severe hypertension, or those having a history of unstable angina, myocardial infarction, cerebrovascular accident, jaundice or renal failure in the preceding six months were excluded. After an initial 2 week placebo period, patients were administered Diabecon (D-400), 2 tablets twice daily before lunch and dinner. Anti-diabetic drugs were continued in those patients who were already taking them, and the dosage of these drugs was modified according to changes in blood sugar on subsequent visits. In case of newly detected diabetics (FBS - 120 mg% and PPBS/180mg% after placebo period), Diabecon (D-400) was started at the same dosage and for the same duration. Treatment was continued for a maximum of 2 weeks with fortnightly follow-ups.

The body weight was considered according to Broca’s Index. Diet was advised according to weight and build of the patients. Associated diseases were treated with appropriate drugs, and any interaction of Diabecon (D-400) with these drugs was closely studied. Urine was examined for sugar with Benedict’s solution. Blood sugar was estimated by the Folin Wu method. Fasting (FBS) and postprandial (PP) blood sugar were examined at the end of 2, 4, 8 and 12 weeks of therapy. Total 24-hour urinary albumin excretion and serum bilirubin, alkaline phosphatase, SGPT, SGOT, blood urea, serum creatinine, and serum cholesterol were estimated initially and at the end of the study. RESULTS Twenty patients were freshly detected diabetics, while the other 23 were old diabetics already receiving oral and/or insulin treatment along with other forms of treatment. The pre-treatment characteristics of these 43 patients are shown in Table 1. Nine patients were simultaneously being treated for their ischaemic heart disease, 8 for hypertension, 4 for bronchial asthma and 3 for pulmonary tuberculosis.

Table 1: Showing pre-treatment characteristics Body weight (kg) Mean age

(years)

Sex Before treatment

After treatment

Mean age of onset (years)

Mean duration of

diabetes Fresh cases (n=20)

50.5 ± 2.2 10 M, 10 F 62.5 ± 3.2 61.3 ± 3.0 48.5 ± 2.4 7.65 ± 2.4 (months)

Oral hypoglycaemic ± Insulin treated cases (n=23)

51.7 ± 1.5

12 M, 11 F

65.0 ± 2.1

64.2 ± 2.1

46.2 ± 1.3

5.49 ± 1.1 (Years)

Out of 23 patients already on antidiabetic drugs, 20 were taking glibenclamide or glipizide, 5-10 mg daily. Eight of them were taking, in addition, 25-75 mg of phenoformin. The remaining 3 patients received inj. lente insulin 44 units plus phenformin 25-75 mg. Table 2 and Figure 1 show the effect of D-400 in the 20 newly diagnosed diabetic patients. Eighteen patients (90%) achieved PPBS<180mg% at the end of 12 weeks.

Table 2: Showing effect of Diabecon (D-400) on newly diagnosed diabetic patients (n=20) Fasting blood sugar (FBS) Postprandial blood sugar (PPBS)

Weeks -2 0 12 -2 0 12 142.50

± 9.40 142.05 ± 8.90

98.00 ± 5.30*

221.00 ± 18.30

219.00 ± 16.30

147.00 ± 6.90*

* p<0.001 as compared to the initial zero week readings.

FBS0

50

100

150

200

250

PPBS

Week (-2) Week 0 Week 12

Week (-2) to Week 0 Placebo treatmentWeek 0 to Week 12 Diabecon (D-400) treatment

Fig. 1: Effect of Diabecon (D-400) on fasting andpostprandial blood sugar levels of early diabetic

patients (n=20)

Suga

r (m

g%)

*

*, p<0.005 w.r.t. respective week-0 levels

Table 3 and Figure 2 show the effect of Diabecon (D-400) in the 23 diabetics who were already on antidiabetic medication. Amongst 20 patients on glibenclamide or glipizide, with or without phenoformin, it was possible to completely omit oral hypoglycaemic agents in 16 of them during the study period, while maintaining equally good or better control of their diabetes. In the remaining 4 patients, the dosage of oral hypoglycaemic agents could only be slightly reduced (e.g. 2.5 mg of glibenclamide or glipizide and/or 25 mg of phenformin). These 4 patients were obese and had onset of diabetes before 40 years of age; their diabetes was of 8-10 years’ duration, and earlier they were maintaining only fair control of diabetes (mean PPBS 180 mg%) with a combination of glibenclamide or glipizide, 10 mg and phenformin, 75 mg daily.

Table 3: Showing effect of Diabecon (D-400) on diabetic cases who were already on oral hypoglycaemic and/or insulin (n=23)

Fasting blood sugar (FBS) Postprandial blood sugar (PPBS) Weeks -2 0 12 -2 0 12

133.60 ± 8.70

124.80 ± 6.80

92.50 ± 3.20*

197.90 ± 9.20

194.70 ± 7.30

145.00 ± 5.20*

* p<0.001 as compared to the initial zero week readings.

0

50

100

150

200

250

*

Fig. 2: Effect of Diabecon (D-400) on fasting andpostprandial blood sugar levels of patient receiving

oral hypoglycemic/insulin treatment (n=23)

*, p<0.005 w.r.t. respective week-0 levels

Week (-2) Week 0 Week 12Week (-2) to Week 0 Placebo treatmentWeek 0 to Week 12 Diabecon (D-400) treatmentAHG = Antihyperglycaemic agent

FBS PPBS

Suga

r (m

g%)

In 3 patients receiving insulin + phenformin, it was possible to reduce the dose of insulin from 44 to 36 units and to completely omit phenformin, in 2 patients. The third patient failed to show a similar satisfactory response. Insulin and phenformin had to be continued in the same dosage. This patient was of thin build, had onset of diabetes before 40 years of age, and diabetes for 9 years duration. A smooth and uniform fall in blood sugar was noticeable at the end of the second week only in patients who responded satisfactorily. This could be maintained without marked fluctuations till 12 weeks. No side-effects were observed in any patient and Diabecon (D-400) was well tolerated by all patients, including those who failed to respond satisfactorily. Body weight remained unchanged (Table 1). No deleterious effects were observed on the liver, kidney, haemopoietic functions or ECG findings, except SGPT, which was significantly reduced from 37.5 ± 1.76 IU/L to 30.2 ± 1.66 IU/L (p<0.001). No interaction between Diabecon (D-400) and the other drugs was noticeable when appropriate drugs wee used concurrently with Diabecon (D-400) for treating the various associated conditions. DISCUSSION Diabecon (D-400) is a crude herbal preparation, formulated as per Ayurvedic principles. The main ingredients are Eugenia jambolana, Tinospora cordifolia, Pterocarpus marsupium, Ficus Glomerulata, Momordica charantia, Ocimum sanctum and Gymnema sylvestre which are well known indigenous oral antidiabetic plants1-2. In some earlier experimental studies, Diabecon (D-400) produced a small but significant fall in fasting blood glucose of normal rats. No change was noticed in blood glucose levels after oral glucose load in normal as well as in alloxan-induced diabetic rats. It has been shown to reduce the nephrotoxic effects of alloxan3. It blunts the hyperglycaemic response to adrenaline and potentiates the actions of tolbutamide and insulin by delaying the recovery from hypoglycaemia caused by these agents. Liver glycogen depletion in alloxan-induced diabetic rats is prevented. The suggested probable mode of action is that it reduces glycogenolysis in the liver, probably by interfering with the glucagon mechanism4. While animal toxicity studies have clearly demonstrated lack of toxicity of Diabecon (D-400), teratogenicity and human studies have established its safety for prolonged and chronic use.

In the present study, there was significant reduction in both the fasting and postprandial blood sugar levels after 12 weeks of treatment in both newly diagnosed patients as well as in those taking oral hypoglycaemics (with or without insulin). Diabecon (D-400) satisfactorily controlled 90% of newly diagnosed diabetics. It was possible to withdraw oral hypoglycaemics in 80% and reduce their dosage in the remaining 20%. In 2 patients, insulin dosage could be reduced and the co-administered phenformin omitted. Diabecon (D-400) was safe, well tolerated, and did not produce any evidence of organ toxicity. Although only a small number of patients have been studied, the initial results are encouraging and have confirmed the safety and hypoglycaemic efficacy of the active ingredients. Which of the ingredients was responsible for this favourable response ? We undertook this study to evaluate the efficacy of the total preparation as was made available to us. According to Ayurvedic texts, a combination of substances is used to get the enhanced desired action and eliminate unwanted side-effects. The modification of the active principle’s action by simple diluents is known to modern medicine. These ingredients may aid absorption of the active hypoglycaemic principles or hinder absorption of toxic materials. At present, the complete basis for use of all the ingredients is not clear but the present study shows that the total preparation has beneficial effects in diabetes mellitus as judged by modern objective evaluation. However because of the small number of patients studied, some lacunae remain. We would like to pursue the study in a larger number of patients over a longer duration, so as to identify the substrate of patients in whom the desirable response can be correlated. Instead of fixed dosage as in this study, in future studies, we would also like to carry out dose titration. A well-planned long-term study will then also identify the effect of the compound on diabetic complications. REFERENCES 1. Chopra R.M., Indian medicinal plants; Indigenous drugs of India, 1933.

2. Nadkarni A.K., Materia Medica, 3rd edition 1992; Vol. 1.

3. Singh A., Dixit S.P., Dubery G.P., Alloxan-induced diabetes in rabbits and effects of a herbal formulation Diabecon (D-400). 1993 (communicated to Indian Journal of Pharmacology).

4. Suryakant D.A., Gopumadhavan S., Chauhan B.L., Kulkarni R.D., Mitra S.K. Effect of Diabecon (D-400), a herbal formulation, on blood sugar of normal and alloxan-induced diabetic rats. 1993 (communicated to Indian Journal of Physiology and Pharmacology).