Effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients

Md Arifur Rahaman; Adhir Kumar Das; Sharmistha Ray; Tazin Islam; Nazma Akther; M. A . Jalil Ansari; Indrajit Prasad; Mohammad Saifuddin; Moinul Islam; Mirza Sharifuzzaman

doi:10.4103/bjem.bjem_20_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 2 | Issue : 1 | Page : 51-54

Effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients

Md Arifur Rahaman¹, Adhir Kumar Das¹, Sharmistha Ray¹, Tazin Islam¹, Nazma Akther², M. A . Jalil Ansari³, Indrajit Prasad³, Mohammad Saifuddin³, Moinul Islam³, Mirza Sharifuzzaman³
¹ Department of Pharmacology, Dhaka Medical College, Bangladesh
² Department of Gynae & Obstetrics, Shaheed Suhrawardy Medical College Hospital, Bangladesh
³ Departmentof Endocrinology, Dhaka Medical College, Bangladesh

Date of Submission	20-Dec-2022
Date of Acceptance	14-Jan-2023
Date of Web Publication	24-Feb-2023

Correspondence Address:
Md Arifur Rahaman
Dhaka Medical College, Dhaka
Bangladesh

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjem.bjem_20_22

Abstract

Background: Diabetes mellitus is one of the most common noncommunicable diseases worldwide, which requires management of the symptoms through lifestyle modification and antidiabetic pharmacotherapies. The purpose of this study was to observe the effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients according to baseline HbA1c, fasting blood glucose (FBG), and blood glucose 2 h after breakfast. Methods: An observational study was conducted at Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka, and Outpatient Department of Ibrahim General Hospital, Mirpur, Dhaka, for 1 year (July 2018–June 2019). In total, 110 type 2 diabetic patients were selected purposively. The patients were divided into two groups. In Group I, 55 patients treated with gliclazide (80 mg) and metformin (500 mg) combination therapy twice daily for consecutive 12 weeks, and in Group II, 55 patients treated with insulin (premixed 30/70) twice daily for consecutive 12 weeks. Results: After 12 weeks of treatment, HbA1c level reduced from (mean ± standard deviation) 8.94 ± 0.91 to 7.82 ± 1.86 in Group I and 10.07 ± 1.28 to 7.90 ± 1.01 in Group II. FBG level reduced from 10.05 ± 1.57 to 7.96 ± 1.62 in Group I and 11.61 ± 2.62 to 7.60 ± 1.23 in Group II. Blood glucose 2 h ABF level reduced from 14.00 ± 2.04 to 10.99 ± 1.41 in Group I and 16.70 ± 3.61 to 10.71 ± 1.52 in Group II. In Group I, 36.4% of patients achieved HbA1c target level, 40% of patients achieved FBG target level, and 25.5% of patients achieved blood glucose 2 h ABF target level. In Group II, 29.1% of patients achieved HbA1c target level, 56.4% of patients achieved FBG target level, and 29.1% of patients achieved blood glucose 2 h ABF target level. Conclusions: On the basis of the study findings, patients of both study groups showed an improvement in the overall glycemic control (HbA1c, FBG, and blood sugar 2 h ABF) during the study. Both groups of drugs are effective in controlling blood glucose, but individual group has a unique beneficial effect.

Keywords: Gliclazide-metformin, glycemic control, type 2 diabetes mellitus

How to cite this article:
Rahaman MA, Das AK, Ray S, Islam T, Akther N, Ansari MA, Prasad I, Saifuddin M, Islam M, Sharifuzzaman M. Effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients. Bangladesh J Endocrinol Metab 2023;2:51-4

How to cite this URL:
Rahaman MA, Das AK, Ray S, Islam T, Akther N, Ansari MA, Prasad I, Saifuddin M, Islam M, Sharifuzzaman M. Effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients. Bangladesh J Endocrinol Metab [serial online] 2023 [cited 2023 Jun 7];2:51-4. Available from: https://www.bjem.org/text.asp?2023/2/1/51/370519

Introduction

Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Symptoms of hyperglycemia include polyuria, polydipsia, polyphagia, weight loss, and blurred vision. Complications of diabetes include retinopathy, nephropathy, and peripheral neuropathy. Patients with diabetes have an increased risk of atherosclerotic, cardiovascular, peripheral arterial, and cerebrovascular disease.^[1] About 425 million people have diabetes in the world, and 82 million people in the South East Asian Region; by 2045, this will rise to 151 million. The prevalence of diabetes is increasing in Bangladesh both in urban and rural areas. Majority of adult population in Bangladesh have type 2 diabetes, and they are in risk to develop diabetic complications early.^[2]

Most adults with diabetes have at least one comorbid chronic disease, and up to 40% have at least three. Up to 75% of adults with diabetes also have hypertension. Other common comorbidities of diabetes are dyslipidemia, cardiovascular disease, kidney disease, nonalcoholic fatty liver disease, and obesity.^[3] Type 2 diabetes is the most common form of diabetes mellitus, which accounts for 90%–95% of all diabetes patients. Lifestyle has a great importance to the development of type 2 diabetes mellitus such as obesity, sedentary lifestyle, physical inactivity, smoking, and alcohol consumption.^[4] Dietary and lifestyle modification are the first approach to maintain optimum glycemic control. If the desired level of glycemic control is not achieved with diet and exercise, pharmacological intervention is required. Oral and injectable antidiabetic drugs are used on the basis of effectiveness, cost, risk of hypoglycemia, weight gain, and patient's preference.^[5]

Metformin is established as a first-line monotherapy. It reduced hepatic glucose production, increasing uptake and utilization of glucose in tissues, and improves insulin sensitivity in type 2 diabetic patients. Metformin does not cause weight gain and hypoglycemia. Gliclazide is a second-generation sulfonylurea drug. It stimulates the production of insulin from beta cells of the pancreas and improves insulin resistance in the peripheral target tissues. It causes hypoglycemia and weight gain.^[6] Metformin plus gliclazide combination therapy is effective at improving glycemic control in patients with type 2 diabetes insufficiently controlled by monotherapy.^[7]

Insulin therapy reduces microvascular complications and lowers macrovascular risk in type 2 diabetes. Weight gain and hypoglycemia are associated with insulin therapy. Hypoglycemia may occur from a mismatch between insulin and diet.^[8]

This study gives an idea about the effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients.

Methods

This observational hospital-based study was conducted at Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka, and the Outpatient Department of Ibrahim General Hospital, Mirpur, Dhaka. The study was carried out for 1 year (July 2018–June 2019). Ethical clearance was taken from the Ethical Review Committee of Dhaka Medical College Hospital and Ibrahim General Hospital authority. In total, 110 type 2 diabetic patients (age: 30–70 years) were selected purposively. The patients were divided into two groups. In Group I, 55 patients treated with gliclazide (80 mg) and metformin (500 mg) combination therapy twice daily for consecutive 12 weeks, and in Group II, 55 patients treated with insulin (premixed 30/70) twice daily for consecutive 12 weeks.

Baseline data of glycemic status HbA1c, fasting blood glucose (FBG), and blood glucose 2 h after breakfast were recorded in a data collection form during the first visit. About 100 patients were interviewed in each group, and their baseline data were recorded during the first visit. Then, the patients were counseled for a follow-up visit in the same diabetes center after 12 weeks with their investigation reports. In follow-up visit, information of HbA1c, FBG, blood glucose 2 h after breakfast, and any history of hypoglycemia in the past 12 weeks was recorded in the data collection form. During follow-up visit, about 45 patients were dropped out in each group because some patients did not come in follow-up and some did not have any investigation which was advised.

All relevant information was collected, completed, and compiled. Collected data were analyzed by SPSS 22.0 (IBM Corp. (2013) IBM SPSS Statistics for Windows, USA). The Student's t-test and Chi-square test were done. P ≤ 0.05 was considered statistically significant at 95% confidence interval.

Results

In this study, the mean age of the patients was 47.69 ± 8.58 years in Group I and 50.78 ± 10.19 years in Group II. Of 110 cases, male patients were predominant in both groups. In Group I, males were 31 (56.4%) and females were 24 (43.6%), and in Group II, males were 29 (52.72%) and females were 26 (47.27%). Most of the respondents were housewives, 22 (40%), in both groups. In both groups, 21 (38.2%) respondents had completed their Secondary School Certificate (SSC). Large numbers of respondents have a positive family history of diabetes mellitus. In Group I, family history was positive in 20 (36.4%), and in Group II, 23 (41.8%) respondents had a positive family history. In this study, the mean duration of diabetes of the patients was 3.93 ± 2.6 years in Group I and 5.38 ± 4.96 years in Group II.

In this study, it was observed that after 12 weeks of treatment, the mean HbA1c level significantly reduced from 8.94 ± 0.91% to 7.82 ± 1.86% in Group I and 10.07 ± 1.28% to 7.90 ± 1.01% in Group II (P = 0.001) [Table 1]. The mean FBG level significantly reduced from 10.05 ± 1.57 to 7.96 ± 1.62 in Group I and 11.61 ± 2.62 to 7.60 ± 1.23 in Group II (P = 0.002) [Table 2]. The mean blood glucose 2 h ABF level significantly reduced from 14.00 ± 2.04 to 10.99 ± 1.41 in Group I and 16.70 ± 3.61to 10.71 ± 1.52 in Group II (P = 0.003) [Table 3].

Table 1: The mean hemoglobin A1c level during the study (12 weeks) in two study groups

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Table 2: The mean fasting blood glucose level in two study groups during the study

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Table 3: The mean blood glucose level of 2 h after breakfast in two study groups during the study

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In this study, the target level of HbA1c was set as <7%, FBG 4.4–7.2 mmol/l, and blood glucose 2 h ABF <10 mmol/l according to the American Diabetes Association guidelines 2019. In Group I, 20 (36.4%) patients achieved HbA1c target level, 22 (40%) patients achieved FBG target level, and 14 (25.5%) patients achieved blood glucose 2 h ABF target level. In Group II, 16 (29.1%) patients achieved HbA1c target level, 31 (56.4%) patients achieved FBG target level, and 16 (29.1%) patients achieved blood glucose 2 h ABF target level. It was observed that 12 (21.8%) patients had experienced hypoglycemia in Group I and 15 (27.3%) patients experienced hypoglycemia in Group II during the study [Table 4].

Table 4: Distribution of respondents by hypoglycemia

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Discussion

This observational hospital-based study was carried out to observe the effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients. This study showed the highest respondents in the age group of 41–50 years which occupied 26 (47.3%) in Group I and the highest respondents in the age group of 51–60 years which occupied 17 (30.9%) in Group II. These results are near to findings of Zakia et al., 2013, in which majority (50.7%) of patients were in the age group of 41–55 years.^[9] Majority of patients were male. In Group I, males were 31 (56.4%), and in Group II, males were 29 (52.72%). Similar findings were found to the study done by Afroz et al., 2019, which showed male 54.4%, but Safita et al., 2016, showed female patients (56.9%) were more than male patients (43.1%).^[10],[11] Educational status revealed maximum patients in both groups; 21 (38.2%) respondents had completed their SSC. These results are near to findings of Latif et al., 2017, in which majority (34.6%) were SSC.^[12] In case of occupation, the predominant occupation was housewife, 40% in both groups. These results are near to findings of Vanderlee et al., 2016, in which the predominant occupation (56%) was housewife.^[13] In this study, family history was positive in 20 (36.4%) in Group I, and in Group II, 23 (41.8%) respondents had a positive family history. Similar findings were found to the study done by Afroz et al., 2019, in which showed that 34.6% of patients have a positive family history.^[10] In this study showed that the duration of diabetes was (mean ± standard deviation [SD]) 3.93 ± 2.6 years in Group I and 5.38 ± 4.96 years in Group II, which was around similar to the study done by Zakia et al., 2013, where the duration of diabetes was (mean ± SD) 6.3 ± 5.6 years.^[9] Another study done by Afroz et al., 2019, where the duration of diabetes was (mean ± SD) 10.7 ± 7.7 years.^[10]

In this study, it was observed that after 12 weeks of treatment, the mean HbA1c level significantly reduced from 8.94 ± 0.91% to 7.82 ± 1.86% in Group I who were treated with metformin plus gliclazide and 10.07 ± 1.28% to 7.90 ± 1.01% in Group II who were treated with premixed insulin. Similar type of study was conducted by Vaughan et al., 2017, in USA for 12 months found that there was significantly decreased HbA1c level by oral and insulin-treated groups; 11.25 ± 2.1% to 7.73 ± 2.1% in insulin group and 9.40 ± 2.1% to 7.22 ± 1.7% in oral group.^[14]

The mean FBG level significantly reduced from 10.05 ± 1.57 to 7.96 ± 1.62 in Group I and 11.61 ± 2.62 to 7.60 ± 1.23 in Group II. This result is also similar to the study done by Pasquel et al., 2015, which also showed a significant reduction of FBG by oral agents and insulin-treated group.^[15] The mean blood glucose 2 h ABF level significantly reduced from 14.00 ± 2.04 to 10.99 ± 1.41 in Group I and 16.70 ± 3.61 to 10.71 ± 1.52 in Group II. This result is also similar to the study done by Pasquel et al., 2015, which also showed a significant reduction of blood sugar 2 h ABF by oral agents and insulin-treated group.^[15] In this study, the target level of HbA1c was set as <7% according to the ADA guidelines, 2019. 20 (36.4%) patients achieved HbA1c target level (<7%) in Group I and 16 (29.1%) patients achieved HbA1c target level (<7%) in Group II, which was around similar to the study done by Pandit, 2016, in India, which also found that seven of 26 patients (26.92%) of oral therapy achieved HbA1c target level (<7%) and 11 of 34 patients (32.35%) of premixed insulin therapy achieved HbA1c target level (<7%).^[16] Respondents experienced more hypoglycemia that were treated with premixed insulin than with metformin plus gliclazide (27.3% and 21.8%, respectively) in this study, which was around similar to the study done by Pandit, 2016, in India.^[16]

Conclusions

On the basis of the study findings, both groups of drugs are effective in controlling blood glucose, but individual group has a unique beneficial effect. Gliclazide and metformin combination therapy showed a less hypoglycemic effect than premixed insulin; hence, they may be prescribed to the patients who are prone to be hypoglycemic (elderly people and working people who do not take their meal properly). Premixed insulin causes higher reduction of HbA1c, FBG, and blood glucose 2 h ABF than metformin and gliclazide combination. Hence, premixed insulin may be preferred for patients in whom too strict glycemic control is needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	American Diabetes Association. American Diabetes Association standard of medical care in diabetes-2018. Diabetes Care 2018;41:1-159.
2.	Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271-81.
3.	Manzella D. How Comorbid Conditions Can Affect Your Diabetes Care; 2019. Available from: https://www.verywellhealth.com/comorbidity-disease-diabetes-1087365. [Last accessed on 2019 Nov 30].
4.	Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci 2014;11:1185-200.
5.	Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the study of diabetes. Diabetes Care 2015;38:140-9.
6.	Stubbs DJ, Levy N, Dhatariya K. Diabetes medication pharmacology. Br J Anaesth 2017;17:198-207.
7.	Hostalek GU, Schlachter J, Geloneze B. Combination therapy with metformin plus gliclazide in patient with type 2 diabetes. J Diabetes Res Ther 2016;2:1-8.
8.	Swinnen SG, Hoekstra JB, DeVries JH. Insulin therapy for type 2 diabetes. Diabetes Care 2009;32 Suppl 2:S253-9.
9.	Zakia S, Ali MA, Akther MS, Uddin MS, Haque MM. Study of evaluation for the management of diabetes in Bangladesh. Pharmacol Pharm 2013;4:355-61.
10.	Afroz A, Ali L, Karim MN, Alramadan MJ, Alam K, Magliano DJ, et al. Glycaemic control for people with type 2 diabetes mellitus in Bangladesh – An urgent need for optimization of management plan. Sci Rep 2019;9:10248.
11.	Safita N, Islam SM, Chow CK, Niessen L, Lechner A, Holle R, et al. The impact of type 2 diabetes on health related quality of life in Bangladesh: Results from a matched study comparing treated cases with non-diabetic controls. Health Qual Life Outcomes 2016;14:129.
12.	Latif ZA, Ashrafuzzaman SM, Amin MF, Gadekar AV, Sobhan MJ, Haider T. A Cross-sectional study to evaluate diabetes management, control and complications in patients with type 2 diabetes in Bangladesh. BIRDEM Med J 2017;7:17-27.
13.	Vanderlee L, Ahmed S, Ferdous F, Farzana FD, Das SK, Ahmed T, et al. Self-care practices and barriers tocompliance among patients with diabetes in a community in rulal Bangladesh. Int J Diabetes 2016;36:320-6.
14.	Vaughan EM, Moreno JP, Hyman D, Chen TA, Foreyt JP. Efficacy of oral versus insulin therapy for newly diagnosed diabetes in low-income settings. Arch Gen Intern Med 2017;1:17-22.
15.	Pasquel FJ, Powell W, Peng L, Johnson TM, Sadeghi-Yarandi S, Newton C, et al. A randomized controlled trial comparing treatment with oral agents and basal insulin in elderly patients with type 2 diabetes in long-term care facilities. BMJ Open Diabetes Res Care 2015;3:e000104.
16.	Pandit A. Comparative effectiveness of multi oral antidiabetic drugs versus insulin therapy for glycemic control in type 2 diabetes mellitus. Asian J Pharm Clin Res 2016;9:262-4.