International Research Journal of Pharmaceutical and Biosciences

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International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 5 (6) 34

RESEARCH ARTICLE

International Research Journal of Pharmaceutical and Biosciences

Pri

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ISSN: 2394 -5826

http://www.irjpbs.come-ISSN: 2394 - 5834

A STUDY ON SAFETY AND EFFICACY OF BIGUANIDE WITH SULFONYLUREAS IN

TYPE-II DIABETES MELLITUS PATIENTS

1_{M.Rangapriya*,}1_{Manaswini Pasupuleti,}1_{Maria Eldho ,}1_{Merin Thomas ,}

1_R.Nandhini

1_{Department of Pharmacy Practice, SwamyVivekanandha College of Pharmacy, Tiruchengode –637205.}

Article info Abstract

ABSTRACT: AIM: To evaluate the safety and effectiveness of Metformin, Glimepiride compared with combination of drugs (Metformin+Glimepiride) treated in patients with type 2 diabetes mellitus in order to evaluate the risk of cardio vascular disease and the differentiation in GFR. MATERIALS AND METHODS: A prospective observational study was carried out for the period of six months. A total of 156 patients who were prescribed either Metformin, Glimepiride and Metformin + Glimepiride were included in the study. Therefore, 53 patients in MET, 51 patients in Glimepiride and 52 patients in Metformin + Glimepiride.We considered the parameters like BMI, blood glucose level, blood pressure, lipid profile, serum creatinine levels. From the data collected we evaluated the safety and efficacy of the regimens. RESULTS: In this study, patients with Type 2 DM who were on Glimepiride observed higher risk of cardiovascular diseases followed by patients who were on combination therapy of Metformin+Glimepiride compared to those who were treated with Metformin. In our study there are moderate changes in GFR and significant increase in serum creatinine levels in the Glimepiride group which may add risk to microvascular events (Diabetic nephropathy) in that group. CONCLUSION: The patient under Glimepiride treatment was more prone to the cardiovascular risk and microvascular risk compared to the Metformin group and combination group (Metformin+Glimepiride)The study concluded with Metformin monotherapy was found to be safe and effective. KEYWORDS: Metformin, Glimepiride, Type 2 DM patients, cardiovascular disease,

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International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 5 (6) 35 INTRODUCTION

Diabetes mellitus is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period [1].Diabetes is the most common endocrine disorder. It occurs due to improper function of pancreas where it limits its production of insulin or due to the inefficient uptake of insulin by the cells of the body [2].It is characterized by hyperglycemia or elevated blood glucose (blood sugar) level. Human body function best at a certain level of sugar in the bloodstream [3].The consumed food gets breakdown and the glucose enters into the blood. The glucose in the blood moves into the body cells with the help of insulin. On uptake of blood glucose by the cells is used for the functions of the body or stored for future use. In a diabetic patient there would be malfunction of insulin, but all the diabetic patients are not affected with the same [4].

This study describes the safe and effective use of oral hypoglycemic medication of Metformin (500mg), Glimepiride (2mg) and combination of Metformin with Glimepiride (500mg+2mg). The study allows assessment of cardiovascular risk and differentiation in glomerular filtration rate (GFR).

TYPE 2 diabetes mellitus has an indirect impact on increasing the risk of cardiovascular disease and renal impairment. Evaluation of medication compliance and adherence can help in the decrease of associated risks. Therefore identification of risk factors can help the patient in improving patient quality of life

METERIALS AND METHODS

The study was a prospective observational study conducted in the department of General Medicine at Vivekanandha Medical Care Hospital, Elayampalayam, Tiruchengode. The proposal was approved by Institutional Ethical Committee (IEC) and written Informed consent was obtained from each patient before enrollment. The duration of the study was 6 months from February 2019 to July 2019. The study was carried out approximately in 156 patients having Type 2 Diabetes Mellitus. We included Patients of either gender of age group above 18 years. Patients with type 2 diabetes under treatment of Metformin, Glimepiride and Metformin + Glimepiride and excluded the Patients on other anti-hyperglycemic drugs for treatment of diabetes, Patient with previous cardiovascular diseases and renal disease, Pregnancy and lactating women. Study was conducted by taking patients who were accordingly fit to the inclusion criteria and were divided into three groups (n=156). First group included subjects on metformin (n=53), second group included subjects on Glimepiride (n=51) and third group followed the subjects on combination of drugs (Metformin+Glimepiride) (n=52) and the data was collected in specially designed proforma which include the following details:

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International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 5 (6) 36 Demographic details: Name, Age, Sex, OP no, Reason for admission , past medical and medication

history, family and social history, diagnosis, therapeutic chart and discharge summary, BMI, blood pressure, lipid profile, blood glucose level, serum creatinine levels.

Blood sample collection: Renal blood samples were collected at the time to measure various bio

markers including fasting blood sugar, post prandial glucose, total cholesterol, triglycerides, LDL and serum creatinine. The evaluation of cardio vascular risk was done based on considering the parameters and ASCVD risk estimator plus to gauge 10 year risk of developing heart disease and the evaluation of differentiation in glomerular filtration rate (eGFR) was calculated by CKD-EPI equation using mobile application.

Statistical analysis: Microsoft excel and computerized statistical package of graph pad instant

version 3.10 were use to analyse the demographic data and parameters and values are represented as mean ±SD (Standard Deviation)

RESULTS

Among the study population, 105(67.3%) were males and 51(32.7%) were females. Gender wise distribution shows that males were prone to disease. The mean (±SD) age of total study population in metformin group (55.6±9.6) out of which 40(75.5%) were male and 13(24.5%) were female, in glimepiride group (63.9±10) out of which 30(58.8%)were male and 21(41.2%) were female and in metformin+glimepiride (62.4±9.4) out of which 35(67.3%) were male and 17(32.7%) were female.

Table 1: Sex distribution between treatment groups

GENDER METFORMIN GLIMEPIRIDE METFORMIN+ GLIMEPIRIDE

MALE 40(75.5%) 30(58.8%) 35(67.3%)

FEMALE 13(24.5%) 21(41.2%) 17(32.7%)

Considering the social history of participants 45(28.85%) were alcoholic 40(26.64%) were smoker, 23(14.74%) were alcoholic+smoker, 18(11.54%) were tobacco chewer and a total of 30(19.23) patients were neither with any social habits.

Table 2: Categorization of social habits among population

SOCIAL HISTORY NO OF PATIENTS

(n=156) PERCENTAGE (%) ALCOHOLIC 45 28.85 SMOKER 40 26.64 ALCOHOLIC+SMOKER 23 14.74 TOBACCO CHEWER 18 11.54 NONE 30 19.23

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International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 5 (6) 37 Clinical comparision of blood pressure in treatment groups

On comparison of systolic blood pressure among the treatment groups it is found to have greater percentage difference (2.9%) in the treatment group Metformin comaprtively to the other two treatment groups, Glimepiride (1.2%) and Metformin +Glimepiride (2.7%).

On comparison of diastolic blood pressure among the and in between the treatment groups there is no any noticeable changes took place.

Table 3: Summarization of baseline and endpoint mean systolic and diastolic blood pressure.

GROUPS SYSTOLIC BLOOD PRESSURE DIASTOLIC BLOOD PRESSURE

BASELINE ENDPOINT BASELINE ENDPOINT

METFORMIN 139.9±12.2 135.9±19.2 81.8±15.7 80.4±4.3

GLIMEPIRIDE 142.3±12.8 140.5±8 84.2±14.7 82.3±9

METFORMIN+ GLIMEPIRIDE

144.3±13.8 140.4±12 79.6±15.4 81.3±8

Clinical comparisons of plasma blood glucose levels in treatment groups.

When mean of plasma blood glucose are compared among the treatment groups of total 156 Type 2 DM patients, there is significant changes in both Fasting blood glucose level and post prandial blood glucose level when their baselines are compared with their end points. Out of all three treatment groups there is significant change in group Metformin in its PPG levels on comparison of its endpoint to other treatment groups.

Table 4: Clinical comparison of plasma blood glucose levels in treatment groups

Groups Baseline End of the study

FPG PPG FPG PPG

METFORMIN 152.01±19.27 267.38±31.27 130.8±16.38 168.84±8.06

GLIMEPIRIDE 152.55±20.88 271.21±29.82 145.1±20.36 179.65±15.2

METFORMIN +

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International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 5 (6) 38 Clinical comparisons of hba1c in treatment groups.

Among the compared mean of Hba1c of treatment groups all the three groups showed significance variance in their end point from their baseline values, but treatment group Metformin had more significant reduction in Hba1c level when compared to remaining treatment groups.

Table 5: Comparison of HbA1c among the treatment groups

GROUPS HbA1c

BASELINE ENDPOINT

METFORMIN 8.5±1.1 7.29±0.3

GLIMEPRIDE 8.4±1.0 7.81±0.1

METFORMIN+GLIMEPRIDE 8.9±1.2 7.43±0.1

Clinical comparisons of lipid profile in treatment groups.

On comparison of mean of lipid profile among the treatment groups there is no any significant changes in the LDL levels, HDL levels were increased in the treatment group metformin from the baseline value shows significant change when compared to other treatment groups, Triglyceride level and Total cholesterol levels were significantly reduced from their baseline value in the treatment group Metformin comparatively to other treatment groups.

Table 6: Summarization of lipid profile among treatment groups

GROUPS LDL HDL

BASELINE ENDPOINT BASELINE ENDPOINT

METFORMIN 133.7±18.9 130.1±19.3 42.1±3.4 50.3±6.0

GLIMEPRIDE 142.1±11.87 137.3±17.2 49.2±5.2 47.5±6.4

METFORMIN+GLIMEPRIDE 134.3±18.7 131.9±18.2 48.6±2.2 46.1±6.9

GROUPS

TG TC

BASELINE ENDPOINT BASELINE ENDPOINT

METFORMIN 234.7±13.3 221.1±7.9 224.4±19.2 197.9±12.9

GLIMEPRIDE 231.4±14.9 229.1±17.2 225.1±12.7 221.8±12.8

METFORMIN+GLIMEPRIDE 239.5±20.2 231.5±18.5 237.2±19.4 225.8±25.1

Clinical Comparisons of GFR levels in treatment groups.

On comparison of GFR among treatment groups there is no any significant changes found when their baseline values are compared with endpoint values. The mean percentage difference found to

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be greater in the treatment group Glimepiride (4.16%) which shows decline in GFR rate compared to other two treatment groups, Metformin (0.02%), Metformin+ Glimepiride (1.7%).

Table 7: Summarization GFR levels among the treatment groups.

GROUPS GFR

BASELINE ENDPOINT

METFORMIN 71.62±12.04 71.6±13.12

GLIMEPIRIDE 60.05±12.99 57.6±13.12

METFORMIN+GLIMEPIRIDE 65.2±11.6 64.1±12.3

Clinical comparisons of creatinine levels in treatment groups.

On comparison of creatinine levels among the treatment groups there are no any significant changes in their baseline values while there is a significant increase of serum creatinine level in the treatment group Glimepiride when its baseline value compared to its endpoint.

When the comparison done based on the percentage differences between the groups, it is found to have greater percentage difference in the treatment group Glimepiride shows an elevated level of serum creatinine

Table 8: Summarization of serum creatinine levels among the treatment groups.

GROUPS CREATININE

BASELINE ENDPOINT

METFORMIN 0.9±0.3 0.8±0.1

GLIMEPIRIDE 1.0±0.5 1.6±0.5

METFORMIN+GLIMEPIRIDE 1.2±0.5 1.2±0.5

LIST OF ADR EVENT REPORTED DURING STUDY.

Out of 156 patients a total of 24 patients were recognize with ADR, among them 16.7% people are from the group Metformin, 37.5% people are in Glimepirde and 45.8% of people are from the group Metformin+Glimepiride.

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International Research Journal of Pharmaceutical and Biosciences (IRJPBS) 5 (6) 40 Table 9: Summarization of ADR events reported during study.

DISCUSSION

This study describes the safe and effective use of oral hypoglycemic medication of Metformin, Glimepiride and combination of Metformin and Glimepiride. The study allows assessment of cardiovascular risk and differentiation in glomerular filtration rate (GFR).

In this study, patients with Type 2 DM who were on sulfonylurea therapy (Glimepiride) were at higher risk of cardiovascular diseases followed by patients who were on combination therapy (Metformin+Glimepiride) compared to those who were treated with Metformin. The earlier study conducted by Colman Siu Cheung Fung et al., [5]found that patients with Metformin were at lower cardiovascular risk.

In this study, the level of HbA1C showed significant reduction in Metformin + Glimepiride group compared to other two groups this may be one of the risk factor which may increase the macrovascular and microvasular risk in those groups. In this study, FPG and PPBG level shows significant decrease in Metformin monotherapy group compared to that of other two groups. This may be the risk factor for increase in CV as well as microvascular risk in those groups. A significant increase in risk of CV events has been reported in the patients who were on Sulfonylurea monotherapy (Glimepiride) compared with other two groups in the study conducted by Christianne L Roumine et al., [6].

This study showed there was no significant reduction in their lipid profiles in Metformin monotherapy group compared to other treatment groups. This may conform the cardio

ADVERSE DRUG REACTIONS NUMBER OF EVENTS NUMBER OF EVENTS NUMBER OF EVENTS Headache 0 1 2 Hypoglycemia 0 4 3 Nausea 1 1 2 Dizziness 1 2 1 Diarrhea 0 0 1 Arthralgia 0 0 1 Dyspepsia 2 1 1 Total 4 9 11 Percentage 16.7% 37.5% 45.8%

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protective property of Metformin. The total cholesterol is high in Glimepiride group. This may account the cardiovascular risk in that treatment group.

Patients with Type 2 DM were shown higher risk of CV and decreased GFR rate. The study conducted by Anna Solini et al,. [7] reported that age and GFR were associated with cardiovascular events. In our study there were moderate changes in GFR rate and significant increase in Serum creatinine levels in the treatment group of Glimepiride which may add risk to microvascular events like diabetic nephropathy in that group.

CONCLUSION

This prospective observational study was carried out in 156 patients diagnosed with diabetes mellitus and their treatment includes Metformin, Sulfonylurea, and combination of Metformin + Glimepiride therapy. Based on the observed data the general practice allows following assessment of cardiovascular risk, differentiation in glomerular filtration rate and adverse drug reactions associated with diabetes mellitus.

➢ Metformin alone group shows less cardiovascular and microvascular (nephropathy) events when compared to other groups. It may be due to significant reduction in blood sugar and lipid profile in Type 2 DM patients

➢ Glimepiride group shows moderate CV risk and Microvascular risk (nephropathy) compared to other groups which may be due to less reduction of blood sugar and lipid profile in Type 2 DM patients

➢ The combination therapy of Metformin along with Glimepiride shows higher CV risk ratio and higher percentage of microvascular complication.

➢ The percentage of ADR events suspected was significantly low in Metformin group compared to the other two groups.

In the conclusion the cardiovascular risk and microvascular risk (nephropathy) was higher in sulfonylurea monotherapy (Glimepiride) followed by combination therapy (Metformin+

Glimepiride) compared to Metformin monotherapy which was found to be safe and effective drug for long term treatment in type 2 diabetes mellitus patients.

ACKNOWLEDGMENTS

We acknowledge our honorable Chairman and Secretary, VidhyaRathna, RashtriyaRatna, Hind Ratna, Prof. Dr. M. Karunanithi, B. Pharm., MS., Ph.D., D.Litt., for providing all facilities for our study and rendering his noble hand in the upliftment of women education in all the disciplines.

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