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RESEARCH ARTICLE

 

A Comparative Evaluation of Safety, Efficacy and Cost Effectiveness of Three add on Treatment Regimens in Type 2 Diabetics; not Controlled by Metformin Alone

 

Dr. Suraj B1*, Dr. C D Tripathi2, Dr. Krishna Biswas3, Dr. B M Padhy4, Dr. Tarun Arora5

1Department of Pharmacology, ESIC Medical College, Gulbarga, 585106, India

2Department of Pharmacology, VMMC & Safdarjung Hospital, New Delhi, 110029, India

3Department of Endocrinology, VMMC & Safdarjung Hospital, New Delhi, 110029, India

4Department of Pharmacology, AIIMS, Bhubaneswar, Orissa, 751019, India

5Department of Pharmacology, LHMC, New Delhi, 110001, India

*Corresponding Author E-mail: drsurajpanchal@gmail.com

 

ABSTRACT:

Background and objectives: Type 2 diabetes mellitus (T2DM) is progressive multisystem disease requiring multiple antihyperglycaemic agents to attain or maintain glycaemic control. With the increase in incidence of T2DM and availability of a number of drugs as second line therapy there is considerable increase in the use of newer, more costly oral hypoglycaemic agents, which has resulted in substantial increase in associated costs to patients. The present study was aimed to evaluate the safety, efficacy and cost effectiveness of oral antidiabetic regimens.

 

Methods:  This study was an observational, prospective and longitudinal in nature carried out to study the safety, efficacy and cost effectiveness of three add on treatment regimens [i.e with sulfonylurea (group 1), glitazones (group 2) and dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) (group 3)] in patient with T2DM not controlled by metformin alone which included 150 subjects (approximately 50 patient in each group). The comparisons were conducted between these three groups for glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), post prandial glucose (PPG), costs and lipid profile.

 

Results: At week 12, the significant reduction in HbA1c was found in group 1 (-1.19%) when compared to group 2 (-0.71%) and group 3 (-0.70%). Also significantly greater reductions were observed in group 1 in FPG level (-38.88%) when compared to group 3 and in PPG level (-54.08%) when compared to group 2 and group 3. Comparison of three groups showed significant increase in the cost in group 3 as compared to group 1 and group 2, with the highest cost effectiveness measured in group 1 (p<0.0001).

 

Interpretation and conclusions: Group 1 resulted in significantly greater reductions in HbA1c, FPG and PPG levels and highest cost effectiveness when compared with group 2 and group 3 in patients with T2DM.

 

KEYWORDS: Add on, Cost effectiveness, Metformin, Type 2 diabetes.

 

 

INTRODUCTION:

Type 2 diabetes mellitus is progressive multisystem disease in which an individual exhibits varying degree of declining beta cell function, insulin resistance and failure to suppress post prandial glucagon secretion[1].

 

 

Received on 17.11.2014       Modified on 28.11.2014

Accepted on 01.12.2014      © RJPT All right reserved

Research J. Pharm. and Tech. 8(1): Jan. 2015; Page 44-50

DOI: 10.5958/0974-360X.2015.00009.8

According to the Diabetes Atlas 2013 published by International Diabetes Federation, the prevalence of diabetes estimated as per the year 2013 is 382 million worldwide and is estimated to affect some 592 million people by 2035. The number of people with diabetes in India as per 2013 was 62.1 million and this number is expected to rise to 109 million by 2035[2].  

 

Type 2 diabetes mellitus usually requires multiple oral hypoglycaemic agents (OHAs) to attain or maintain glycaemic control. Most current therapeutic guidelines recommend metformin as initial monotherapy for treatment of type 2 diabetes[3].  Insulin secretagogues, such as sulfonylureas (SU), are frequently used as second-line therapy if metformin monotherapy does not achieve acceptable glycaemic control. However, sulfonylureas can lead to an increased risk of hypoglycaemia and weight gain. Therefore OHAs that provide similar glycaemic efficacy as sulfonylureas, can effectively substitute these drugs as second line drugs in combination with metformin but with less hypoglycaemia and weight gain, could improve the management of patients with type 2 diabetes[4].

 

Although, the onset of glucose lowering effect of sulfonylurea monotherapy is relatively rapid compared with thiazolidinediones (TZDs), maintenance of glycaemic targets over time is not as good as monotherapy with either TZD or sulfonylurea[5].  Pioglitazone is often given in combination with metformin when latter fails to maintain glycaemic control. The combination therapy of pioglitazone and metformin appears to be a rational approach that maximizes the established, complimentary benefits of these agents[6]. Such an approach not only leads to better glycaemic control, but also reduces metabolic risk and help in improving cardiovascular disease outcomes[7].  However, one of the chief adverse effects of TZDs is weight gain. It appears to involve mostly peripheral subcutaneous sites, with a reduction in visceral fat depots[8],  the latter being better correlated with insulin resistance. Another complication related to the use of this class of drugs is TZD- induced osteoporosis which appears to be an inhibition of osteoblast differentiation, with a resultant negative effect on cortical bone formation without a change in bone resorption[9].  Recently, controversy has surrounded rosiglitazone due to its association with myocardial infarction[10].

 

DPP-4 inhibitors are small molecules that enhance the effects of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), increasing glucose-mediated insulin secretion and suppressing glucagon secretion[11, 12]. The first oral DPP-4 inhibitor, sitagliptin, was approved by the United States Food and Drug Administration (US FDA) in October 2006 for use as monotherapy or in combination with metformin or TZDs. DPP-4 inhibitors provide a complementary mechanism of action to existing OHAs and demonstrate significant efficacy when added to metformin, SU, or a TZD, with a well tolerated profile, including a low risk for hypoglycaemia and weight neutrality[13].

 

Although the DPP-4 inhibitors have been proved to be effective drugs for T2DM both as monotherapy and in combination therapy, there have been very few studies which have compared DPP-4 inhibitors in combination with metformin against existing established combination therapies for diabetes mellitus. Also, there is paucity of data regarding the cost effectiveness of DPP-4 inhibitors in Indian population.

 

As a number of drugs are available for second line therapy a physician might find it difficult to choose the optimal option available for an individual patient. Moreover, with the introduction of newer antidiabetic drugs, physicians often shift to combination of newer drugs with the aim of achieving of better glycaemic control[14]. However, one important aspect that is usually disregarded is the comparative cost effectiveness of these newer antidiabetic regimens which puts the considerable strain on the patients hailing from various socioeconomic strata. As previous studies had not been conducted to evaluate the cost-effectiveness of treatment with newer antidiabetics, this observational, prospective, study was designed to compare sulfonylurea, thiazolidinediones or DPP-4 inhibitor as an add on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone.

 

MATERIAL AND METHODS:

Study design:

This study was an observational, prospective, longitudinal study conducted in Department of Pharmacology and Department of Endocrinology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, from November 2010 to April 2012. The study was started after obtaining approval from the Institutional Human Ethics Committee [Protocol No.26-10-EC (10/19), CTRI Reference No: REF/2012/09/004034]. The study investigator had no role in choosing the treatment option for the patients and it was at the discretion of the treating physician. Patients of either sex aged 18-70 years with type 2 diabetes mellitus either newly diagnosed or established previously and not controlled by metformin alone with baseline HbA1c ≥7%, needing additional to metformin and willing to provide informed consent were included in the study. Patients of type 1 diabetes, patients on insulin treatment, secondary diabetes, complications on or during treatment plan, known or suspected hypersensitivity to study drugs and co-morbid illness like cardiovascular disease, renal failure and liver disease were excluded.

 

The patients attending the outpatient department (OPD) were screened for the disease and relevant medical and family history. Diabetic complications and co-morbid conditions associated with diabetes were noted. The patients underwent a thorough physical and systemic examination. Baseline laboratory investigations including HbA1c, fasting plasma glucose, post prandial glucose, liver function test, kidney function test, lipid profile and urine investigations were performed. Patients were reviewed with all investigations after two week. All patients fulfilling the inclusion criteria were included in the study and the patients fell into three subcategories as per treatment groups described below.

   

Treatment groups:

Group 1 comprised of patients started on sulphonylurea (Glibenclamide 5mg/ Glimepiride 1mg/Gliclazide 60mg); group 2 was prescribed Pioglitazone 30mg and group 3 was prescribed Sitagliptin 100mg in addition to their usual dose of Metformin.

 

A written informed consent was obtained from all the patients before their enrolment in the study. After enrolment, participants underwent 2-week initial assessment period in which they were asked to understand, follow all the instructions regarding dietary advice, life style changes, periodic monitoring of blood glucose (fasting, postprandial and HbA1c) testing, recognition and management of both hypoglycaemia and hyperglycaemia. All the participants were free to contact the investigators at any point of time during the study period and were also encouraged to report any adverse events as soon as possible. All the necessary data were collected at day 0, 2 week, 1 month, 2 month and 3 month interval after add on therapy. Patients who missed a visit even after telephonic reminder were excluded from the study. Adherence to the therapy was assessed verbally after every visit as per instructions given at initial visit.

 

Study Evaluations:

The three regimens were assessed on the basis of safety, efficacy and the cost effectiveness.

a) Safety Assessments: Safety and tolerability were assessed through the analysis of adverse events related to treatment, laboratory evaluations and body weight on every visit (i.e on day 0, week 2, 1st, 2nd and 3rd month). Patients were counselled regarding the symptoms of hypoglycaemia (e.g. weakness, dizziness, increased sweating, palpitations or confusion) and to immediately contact the investigator. Causality assessment were analysed as per World Health Organisation-Uppsala monitoring Centre (WHO-UMC) causality assessment system[15].

 

b) Efficacy Assessments: Evaluation of efficacy was done based on primary end point i.e change in HbA1c levels at day 0 (pre-evaluation) and after 3 months (post evaluation) and by secondary end point i.e change from baseline in FPG and PPG measured on every visit (day 0, week 2, 1st, 2nd and 3rd month).

 

c) Cost effectiveness: It was calculated in terms of pharmaceutical cost on daily basis in each patient for a period of three months in each group. The cost incurred in each group for a 1% reduction in HbA1c was compared. This was done by recording brand names, dose and the frequency of the drugs prescribed. Dose of a drug changed based on blood glucose level were also taken into consideration. Individual cost was calculated by finding the cost of unit dose of a drug from drug compendium Current Index of Medical Specialties (CIMS, Jan-April 2011) and multiplying it by number of units consumed over 3 months to get individual cost. Cost effectiveness for particular patient was calculated by dividing the individual pharmaceutical cost by the change in HbA1c observed in that patient during the study period[16]. Average cost effectiveness were then calculated for group 1, group 2 and group 3.

Cost effectiveness for individual patient = individual pharmaceutical cost/difference in HbA1c value (i.e difference between pre and post evaluation values)

 

Biochemical parameters:

Estimation of plasma glucose (FPG and PPG) was based on glucose oxidase methods with formation of Oxidized o-Dianisidine a coloured compound measured at 540nm. HbA1c was estimated based on immunoassay with agglutination reaction producing light scattering, measured as an increase in absorbance[17].  The urea was estimated by enzymatic method based on preliminary hydrolysis of urea with urease and by enzymatic assay with glutamate dehydrogenase. A decrease in absorbance resulting from glutamate dehydrogenase reaction is monitored at 340nm. Methods for Creatinine assays are based on alkaline picrate methods Jaffe with orange red complex measured between 490nm and 500nm. (18) Cholesterol determination was based on enzymatic method after hydrolysis and oxidation with formation of coloured component measured at about 500nm. The Triglycerides are determined after enzymatic hydrolysis with lipases and glycerophosphate dehydrogenase reaction with the formation nicotinamide-adenine dinucleotide measured at 340nm. HDL and LDL are estimated using a combination of ultracentrifugation and polyanion precipitation[19].  AST and ALT were measured by International Federation of Clinical Chemistry (IFCC) method[20].

 

These were analysed by a fully automated analyzer (BECKMAN COULTER SYNCHRON UniCel DxC 800).

 

Statistical analysis:

All the parameters were analyzed by using computer software SPSS 16.0 version. The data collected at 0 week was used as the baseline against which changes at 3rd month were compared. Changes in HbA1c, weight, body mass index (BMI), FPG, PPG, blood urea, serum creatinine, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) and lipid profile were compared by one way ANOVA followed by post hoc Bonferroni test. All non-parametric data like sex, family history and adverse event were analyzed by Mann-Whitney test for comparison between groups. All the results are presented as mean + standard deviation unless otherwise specified. P value of <0.05 was considered statistically significant.

 

RESULTS:

Patient Disposition and Characteristics:

Of 187 patients screened, 150 patients completed the 12 week study. They were allotted into three groups as Metformin + Sulfonylurea (Group 1), Metformin + Glitazones (Group 2) and Metformin + DPP4 inhibitors (Group 3). Table I summarizes the baseline demographics, efficacy endpoint data and biochemical parameters of the study population. There were no significant differences in mean duration of diabetes between the groups. The baseline efficacy endpoints in all the three groups were comparable. The baseline biochemical parameters were comparable except for HDL levels in group 3 which was significantly higher than the group 1 (p<0.004) and blood urea level which was significantly higher in group 2 than group 1 (p<0.025).

 

Efficacy:

The mean reduction in HbA1c from baseline at week 12 was -1.19 + 0.67 %, -0.71 + 0.47 % and -0.70 + 0.83 % in group 1, group 2 and group 3 respectively (Table II). The results of our study showed that the reduction in group 1 was significant when compared to group 2 [(p < 0.002), 95% CI (0.15, 0.81)] and group 3 [(p< 0.001), 95% CI (0.16, 0.82)].

 

The mean change in FPG from baseline at week 12 was -38.88 + 15.22 mg %, -26.36 + 41.05 mg % and -20.48 + 28.86 mg % in group 1, group 2 and group 3 respectively (Table II). However, the reduction in group 1 was significant when compared to group 3 [(p< 0.009), 95% CI (3.66, 33.26)]. The mean change from baseline in PPG at week 12 was -54.08 + 57.09 mg%, -24.78 + 38.98 mg% and -19.44 + 33.01mg% in group 1, group 2 and group 3 respectively (Table II). However, the reduction in group 1 was significantly higher when compared to group 2 [(p < 0.002), 95% CI (8.55, 50.05)] and group 3 [(p< 0.0001), 95% CI (13.89, 55.39)]. In addition, there were significant changes in some of the biochemical parameters measured at the baseline in the three groups. The results showed that the mean change from baseline in HDL-C at week 12 in group 2 was 2.40 + 2.79 mg/dl which was significant as compared to group 3 [(p< 0.012), 95% CI (-2.56, -0.24)]. However, there was significant increase in TG levels in group 1 (10.50 + 26.99 mg/dl) when compared to group 2 (15.70 + 11.02 mg/dl) [(p< 0.0001), 95% CI (-35.75, -16.65)] and group 3 (9.28 + 17.79 mg/dl) [(p< 0.0001), 95% CI (-29.33, -10.23)] at week 12. There were no significant changes in other biochemical parameters at week 12 as compared to baseline.

 

 

Table I: Baseline demographics, efficacy endpoint data and biochemical parameters of patients in the study groups.

Characteristic                                                     Group 1                        Group 2                        Group 3

                                                                                (n=50)                                               (n=50)                                                (n=50)

Age (yr)                                                                  48.94+9.34                                       47.40+10.10                                     46.86+9.57

Sex                                                                                                                                                          

Male                                                                       19 (38%)                                           21 (42%)                                                                 34 (68%)a                  

Female                                                                                                    31(62%)                                            29 (58%)                                           16 (32%)

Body Weight (Kg)                                                63.76 + 9.71                                     65.39 + 10.09                                   65.02 +12.15

BMI (Kg/m2)                                                        28.92 + 2.86b,c                                                   27.19 + 1.92                                     27.23 + 3.65

Duration of T2DM (yr)                                       2.80 + 3.01                                        2.72 + 2.43                                        3.36 + 3.55 

HbA1c (%)                                                            8.66 + 1.44                                        8.54 + 1.10                                        8.22 + 0.99

FPG (mg %)                                      195.0 + 61.82                                   181.64 + 50.27                                 183.98 + 57.94

PPG (mg %)                                                          289.36 + 92.41                                 256.48 + 74.80                                 273.80 + 72.50

Blood urea (mg/dl)                                              25.90 + 6.80                                     29.48 + 7.79 a                                                     27.58 + 5.28

Serum creatinine (mg/dl)                                    0.73 + 0.19                                        0.77 + 0.13                                        0.73 + 0.12

AST(mg/dl)                                                           28.22 + 9.14                                     29.58 + 8.70                                     31.54 + 7.09

ALT(mg/dl)                                                           32.60 + 10.93                                   29.62 + 8.45                                     30.70 + 7.88

Sr.Total cholesterol (mg/dl)                               177.44 + 33.31                                 193.74 + 35.96                                 186.70 + 39.85

HDL (mg/dl)                                                         37.62 + 7.59                                     39.46 + 6.49                                     42.02 + 6.11a

LDL (mg/dl)                                                          106.38 + 29.24                                 118.98 + 33.18                                 111.92 + 39.68

TG(mg/dl)                                                             157.52 + 50.45                                 172.06 + 53.60                                 182.98  + 73.88

Data are expressed as mean ± standard deviation or frequency [n (%)] unless otherwise indicated. BMI, body mass index; FPG, fasting plasma glucose; PPG, post prandial glucose; HbA1c, glycosylated haemoglobin; AST, aspartate aminotransaminase; ALT, Alanine aminotransaminase; HDL, High Density Lipoproteins, LDL, Low Density Lipoproteins; TG, Triglycerides. a - denotes p < 0.05 compared to group 1, b - denotes p < 0.05 compared to group 2, c - denotes p < 0.05 compared to group 3

 

Table II: Key efficacy results

                                                                       Week 0 (baseline)                                    Week 12                                            Mean difference

                                                                       (mean + SD)                                            (mean + SD)                                       (mean + SD)

HbA1c (%)                                                                          

  Group 1                                                      8.66 + 1.44                                               7.47 + 0.94                      -1.19 + 0.67a

  Group 2                                                      8.54 + 1.10                                               7.82 + 1.05                      -0.71 + 0.47

  Group 3                                                      8.22 + 0.99                                               7.52 + 0.89                      -0.70 + 0.83

FPG (mg %)

  Group 1                                                      195 + 61.82                                             156.12 + 44.68                                   -38.88 + 15.22b

  Group 2                                                      181.64 + 50.27                   155.28 + 45.77                                   -26.36 + 41.05

  Group 3                                                      183.98 + 57.94                   163.56 + 51.62                                   -20.48 + 28.86  

PPG (mg %) 

  Group 1                                                      289.36 + 92.41                      235.28 + 70.23                                 -54.08 + 57.09a

  Group 2                                                      256.48 + 74.80                      231.70 + 71.65                                 -24.78 + 38.98

  Group 3                                                      273.80 + 72.50                      254.80 + 64.54                                 -19.44 + 33.01                                                                                                                           

FPG, fasting plasma glucose; PPG, post prandial glucose; HbA1c, glycosylated haemoglobin

a - denotes p < 0.05 compared to group 2 n 3, b - denotes p < 0.05 compared to group 3

 

 

 

 

Safety and Tolerability:

A total of 28 patients in the study population reported adverse events, 15 in group 1, 7 in group 2 and 6 in group 3. Causality assessment was done for each of the adverse events using the WHO causality assessment scale. All the adverse events had possible causal relationship with study drugs. No dechallenge or rechallenge was done in any case. All the adverse events were managed symptomatically and did not require either interruption or stoppage of treatment. None of the adverse events were serious in nature. Most hypoglycaemic episodes were reported in group 1 which accounted for 9 (18 %) followed by gastrointestinal disorder in 6 (12 %) patients.

 

Of the total 9 hypoglycaemic episodes, four patients missed doses during hypoglycaemic event rest managed as per instructions given at initial visit. The adverse events noted in group 2 were headache in 5 (10 %) and oedema in 2 (4 %) patients; and in group 3 gastrointestinal disorder accounting for 5 (10 %) and headache in 1 (2 %) patients. Among patients with measurements at week 12, body weight decreased from baseline with group 3 [(mean difference = -1.04+1.10 kg)] when compared to group 1 [(p< 0.0001), 95% CI (1.52, 3.12)] and group 2 [(p< 0.0001), 95% CI (2.43, 4.03)] and increased from baseline with group 1 [(mean difference = 1.28 + 2.35 kg)] when compared to group 2 [(p< 0.019), 95% CI (0.11, 1.71)] and group 3 [(p< 0.0001), 95% CI (-3.12, -1.52)]. Among the LFT parameters, alanine aminotransferase (ALT) levels increased significantly in group 3 [(mean difference = 3.46 + 3.50 IU/l)] when compared to group 1 [(p< 0.013), 95% CI (-3.85, -0.35)]. The mean ankle circumference [(mean difference = 0.206 + 0.24 cms)] increased significantly in group 2 when compared to group 1 [(p< 0.009), 95% CI (-0.26, -0.03)] and group 3 [(p< 0.012), 95% CI (-0.26, -0.02)].

 

Cost effectiveness:

The average cost incurred for a mean reduction in HbA1c of 1.19 % in each subject in group 1 was INR 823.12, INR 927.99 for mean reduction in HbA1c of 0.71 % in group 2 and INR 4123.89 for a mean reduction in HbA1c of 0.70 % in group 3. Comparison of cost effectiveness in three groups showed significant increase in the cost in group 3 as compared to group1[(p< 0.0001), 95% CI (-7738.08, -5132.64)] and group 2 [(p< 0.0001), 95% CI (-6940.22, -4334.79)].

 

Table III: Comparison of average costs and cost effectiveness in three treatment groups

Treatment             Average cost of                    Cost effectiveness       

Group                     drugs (INR)                         (INR)  (mean + SD)

                               (mean + SD)

Group 1                 823.12 + 386.13                       860.74 + 854.39a

Group 2                 927.99 + 225.64                       1658.59 + 1620.27b

Group 3                 4123.89 + 0.0                            7296.10 + 4283.46

a - denotes p < 0.05 compared to group 3, b - denotes p < 0.05 compared to group 3

 

 

DISCUSSION:

Diabetes mellitus is a chronic metabolic disorder which involves treatment with antidiabetic drugs for a long duration which incurs a considerable expenditure on the patient. With the introduction of newer antidiabetic drugs, physicians often shift to combination of newer drugs. This observational, prospective, study was designed to compare the efficacy, safety and cost-effectiveness of sulfonylurea, thiazolidinediones or DPP-4 inhibitor as an add on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone. Our findings show that HbA1c lowering efficacy and cost effectiveness of sulfonylurea and metformin combination is superior to that of pioglitazone and metformin or sitagliptin and metformin combination. The reduction in HbA1c seen in our study in the sulfonylurea and metformin group was 1.19 % with a baseline value of 8.66 + 1.44%. It was found to be in concordance with the earlier studies conducted by Pareek et al [21] and Shimpi et al [22]  who observed a reduction of 1.07 % and 1.37 %  in 3 month duration respectively. Another study of a combination of pioglitazone with metformin carried out by Einhorn et al [23] over 16 week has showed an HbA1c reduction of 0.83 % which is nearly similar to the reduction seen in our study.  Charbonnel et al [24] also showed that adding pioglitazone therapy to existing metformin therapy improved glycaemic control and this improvement was sustained over 2 years of controlled therapy. A similar reduction in HbA1c of 0.7% in sitagliptin and metformin group was also seen in study carried out by Srivastava et al[25] and Scott et al [26] who observed a reduction of 0.64% and 0.73% of 18 weeks duration respectively. This provided the evidence that the reduction in HbA1c over 3 months duration was highest in group 1 treated with combination of sulfonylurea and metformin.

 

The reduction in FPG (38.88 + 15.22 mg%) obtained with sulfonylurea and metformin group with the baseline value of 195.0 + 61.82 mg% was found to be slightly lesser than study conducted by Shimpi et al [22] and Pareek et al [21] who observed a reduction of 54 mg/dl and 67 mg/dl over 3 month duration respectively which may be due to low adherence of drug or inappropriate titration of the initial dose level. The reduction in FPG observed in pioglitazone with metformin group in our study was found to be similar with study of pioglitazone combined with metformin done by Einhorn et al [23] who observed a reduction of 38 mg/dl at the end of 16 weeks. The reduction in FPG obtained with sitagliptin with metformin group was consistent with study of sitagliptin combined with metformin done by Hermansen et al [27] who observed a reduction of 20.1 mg/dl at the end of 24 week period.

 

The most common adverse events noted in our study were hypoglycaemia (18%) in sulfonylurea with metformin group, followed by headache (10%) and gastrointestinal disorder (10%) in pioglitazone with metformin group and sitagliptin with metformin group respectively. The incidence of hypoglycaemia and gastrointestinal disorder was slightly higher than the previous study conducted by Charbonnel et al (24) where it was 11.5%. All the hypoglycaemic events in our study were minor in nature.

 

Given the large, growing population of patients with type 2 diabetes, suboptimal use of second-line antidiabetes drugs is likely to have a detrimental effect on both health outcomes and the cost-effective use of drugs. Therefore, there is a need for clear recommendations based on clinical and cost-effectiveness evidence to guide second-line therapy for patients with type 2 diabetes inadequately controlled on metformin. In our study, the average cost incurred for a mean reduction in HbA1c of 1.19 % in subjects in group 1 was INR 823.12, INR 927.99 for mean reduction in HbA1c of 0.71 % in group 2 and INR 4123.89 for a mean reduction in HbA1c of 0.70 % in group 3. Comparison of costs between three groups showed statistical significance between group 1 and group 3 and between group 2 and group 3 (p < 0.0001). Similar pattern was also observed when cost effectiveness was compared between the groups and the values were INR 860.74, 1658.59, 7290.10 in group 1, group 2 and group 3 respectively. Therefore, this provides evidence that sulfonylurea when used with metformin combination is most cost effective than pioglitazone and metformin combination and sitagliptin and metformin combination. Together the results of our study showed that the combination of sulfonylurea and metformin is more efficacious and significantly more cost effective than pioglitazone and metformin combination and sitagliptin and metformin combination. Similar study was conducted by Khushali G et al which calculated the cost of therapy for diabetic patients[28]. However, the numbers of DPP IV inhibitors taken into consideration were less.

 

However our study had certain limitations such as non randomized, open label study design and relatively short study duration carried out in a relatively small patient sample in a single government hospital. Nevertheless there are very few studies from India which calculated the actual cost effectiveness of various antidiabetic medications used in management of T2DM. Further studies of the similar kind with larger sample size and multiple centres will strengthen our findings and may help Indian physicians in choosing the optimal antidiabetic regimen for T2DM patients.

 

CONFLICT OF INTEREST:

None

ACKNOWLEDGEMENT:

We authors thank the participants of the study.

 

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