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Cost-Minimization Analysis of Metformin and Acarbose in Treatment of Type 2 Diabetes

      Abstract

      Background

      Metformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus (T2DM) per international guidelines with proven efficacy, safety, and cost-effectiveness. However, little information comparing it with acarbose exists.

      Objective

      To study the cost-effectiveness of metformin and acarbose—two extensively adopted agents—in treating T2DM.

      Methods

      Cost-minimization analysis was conducted on the assumption that metformin and acarbose have equivalent clinical effectiveness. The cost of treatment was detected and evaluated from a payer’s perspective. In sensitivity analyses, several clinical scenarios were developed according to clinical practices and physicians’ prescribing behaviors in China.

      Results

      Metformin can save annual treatment costs by 39.87% to 40.97% compared with acarbose. Under a wide range of assumptions on utilization profile and physician prescribing behavior, it saves costs by 19.83% to 40.97% in patients whose weight is 60 kg or less and by 39.87% to 70.49% in patients whose weight is more than 60 kg, which corroborates the results that metformin is more cost-effective than acarbose.

      Conclusions

      Metformin appears to provide better value for money than does acarbose. Findings from this study are consistent with those from previous studies that metformin is undoubtedly the first choice in the management of T2DM, with significant glucose-lowering effects and low treatment costs.

      Keywords

      Introduction

      Diabetes is one of the common chronic diseases worldwide [
      1996–2000 National Diabetes Prevention Program.
      ]. China leads among the countries with the highest prevalence of diabetes. In 2010, the prevalence of diabetes in Chinese adults 18 years and older was 11.6% (113.9 million) [
      • Xu Y.
      • Wang L.M.
      • He J.
      • et al.
      Prevalence and control of diabetes in Chinese adults.
      ]. Because of the long duration and expensive treatment, diabetes not only affects patients’ quality of life but also brings a heavy economic burden to both the family and the society. A study on the epidemic and economic burden of diabetes in China [
      • Hu S.L.
      • Liu G.E.
      • Xu Z.R.
      • et al.
      Current status of epidemic and economic burden of diabetes mellitus in China.
      ] indicates that the average annual growth rate of direct medical cost of diabetes was 19.9% in recent years, which was higher than the gross domestic product and national health care expenditure growth over the same period, ranking the second in all surveyed chronic diseases.
      Type 2 diabetes mellitus (T2DM) accounts for at least 90% of all cases of diabetes [

      International Diabetes Federation. Types of diabetes. Available from: http://www.idf.org/about-diabetes. [Accessed March 10, 2014].

      ]. It has brought great burden in terms of health care cost and socioeconomic consequences, reaching $26.0 billion in 2007 in direct medical costs and predicted to be $47.2 billion by 2030 in China [
      • Wang W.
      • McGreevey W.P.
      • Fu C.
      • et al.
      Type 2 diabetes mellitus in China: a preventable economic burden.
      ]. Glycemic control in patients with T2DM is directly related to the occurrence of diabetes-related complications and the extent of damage to target organs, and it is the key point in treating T2DM. When lifestyle interventions can no longer bring about glycemic control, oral hypoglycemic agents are the main methods used for the treatment of T2DM. Owing to the advances in T2DM treatment, there are many kinds of oral hypoglycemic agents available in the market. Each agent has its peculiarity in mechanism and site of action; thus, their glucose-lowering effects and treatment costs for patients vary significantly.
      As a biguanide drug, metformin is the first-line oral hypoglycemic agent for T2DM in compliance with international guidelines with proven efficacy, safety, and cost-effectiveness [
      American Diabetes Association
      Standards of medical care in diabetes--2013.
      ,
      Chinese Diabetes Society
      Chinese guideline for type 2 diabetes prevention (2013).
      ,
      Diabetes Prevention Program Research Group
      Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study.
      ], whereas acarbose, one of the α-glucosidase inhibitors, is recommended as one of the second-line drugs in the treatment of diabetes in China [
      Chinese Diabetes Society
      Chinese guideline for type 2 diabetes prevention (2013).
      ]. In use of oral antidiabetic drugs in China, metformin (53.7%) and α-glucosidase inhibitors (including acarbose, 35.9%), however, are both widely accepted and used either as monotherapy or in combination with other antidiabetic agents [
      • Ji L.
      • Lu J.
      • Weng J.
      • et al.
      China type 2 diabetes treatment status survey of treatment pattern of oral drugs users.
      ]. A possible reason for the popular use of acarbose may be its effect, which is superior in patients eating a relatively high carbohydrate diet, such as Chinese [
      • Zhu Q.
      • Tong Y.
      • Wu T.
      • et al.
      Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an Eastern or Western diet: a systematic meta-analysis.
      ]. Little information exists, however, comparing metformin with acarbose in both clinical effectiveness and cost-effectiveness.
      After a meta-analysis, it was found that glucose-lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin monotherapy is a little better by indirect comparison [

      Gu SY, Xu XC, Shi LZ, et al. Cost minimization analysis of clinical option scenarios for metformin and acarbose in treatment of type 2 diabetes: based on direct and indirect treatment comparison results: ISPOR 6th Asia-Pacific Conference. Available from: http://www.ispor.org/research_pdfs/47/pdffiles/PDB27.pdf. [Accessed March 14, 2015].

      ]. This means that glucose-lowering effects of metformin monotherapy are at least as good as those of acarbose monotherapy. Thus, this study aimed to make an economic evaluation by using a cost-minimization analysis technique to see which drug is more cost-effective.

      Methods

       Estimation of the Cost

      The perspective of the payer was used in this study because both drugs are covered by the payer. Cost was estimated on the basis of treatment schedules from the literature [
      • Chen L.L.
      • Zheng J.
      Comparison of the effect of acarbose, metformin and glipizide on newly diagnosed young type 2 diabetic patients.
      ,
      • Chou W.Z.
      Clinical observation of type 2 diabetes treatment with acarbose.
      ,
      • Hong F.
      The analysis of efficacy and medication of several drugs to treat type 2 diabetes.
      ,
      • Tang Y.
      • Chen F.M.
      The analysis of efficacy and side effects of acarbose and metformin to treat type 2 diabetes.
      ,
      • Wang H.B.
      • Deng X.C.
      • Feng Y.T.
      Clinical observation of diabetes II treatment with acarbose and metformin.
      ,
      • Yang H.L.
      Observation of clinical effect on acarbose to treat type 2 diabetes.
      ,
      • Zhang M.H.
      Treatment effect of metformin and acarbose in patients with type 2 diabetic insulin resistance.
      ,
      • Zhu Z.L.
      • Qiu X.C.
      • Zhu H.P.
      • et al.
      Application of acarbose combined with metformin in treatment of newly diagnosed type 2 diabetes patients.
      ] and prices of both drugs in China; only direct medical costs were included. For metformin (brand name Glucophage, specification 500 mg × 20 tablets), the highest price set by the government is ¥29.2 and the lowest set by the market is ¥24.82; for acarbose (brand name Glucobay, specification 50 mg × 30 tablets), the highest and the lowest price is ¥74.2 and ¥61.92, respectively [

      National Development and Reform Commission Price [2010]. No. 2829: notice on reducing the highest retail prices of several drugs such as ceftriaxone. Available from: http://www.ndrc.gov.cn/zcfb/zcfbtz/201011/t20101130_383648.html. [Accessed May 30, 2014].

      ,

      Notice on publicity for the use of a few drug species (second batch) that are not included in the procurement catalog of essential drugs in medical institutions above secondary in 2013. Available from: http://ypcgzx.jswst.gov.cn/zxxx/6370.html. [Accessed May 30, 2014].

      ,

      National Development and Reform Commission Price [2011]. No. 1670: notice on adjusting the prices and related issues of drugs such as hormone, regulates endocrine and nervous system drugs. Available from: http://www.ndrc.gov.cn/zcfb/zcfbtz/201108/t20110805_427311.html. [Accessed May 30, 2014].

      ,

      Centralized procurement of essential drugs in Beijing in 2012. Available from: http://www.bjmbc.org.cn/index/index.aspx. [Accessed May 30, 2014].

      ]. Both the lowest and highest prices were used to estimate the annual average treatment cost. Because both drugs are common oral hypoglycemic agents and tolerated well and have similar treatment efficacy and gastrointestinal adverse reactions, which can be alleviated by starting at a low dose and escalating the dose gradually [
      Chinese Diabetes Society
      Chinese guideline for type 2 diabetes prevention (2013).
      ,

      Gu SY, Xu XC, Shi LZ, et al. Cost minimization analysis of clinical option scenarios for metformin and acarbose in treatment of type 2 diabetes: based on direct and indirect treatment comparison results: ISPOR 6th Asia-Pacific Conference. Available from: http://www.ispor.org/research_pdfs/47/pdffiles/PDB27.pdf. [Accessed March 14, 2015].

      ,

      Glucophage® (metformin hydrochloride tablets) Glucophage® XR (metformin hydrochloride extended-release tablets) description. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020357s031,021202s016lbl.pdf. [Accessed March 20, 2014].

      ,

      Precose® (acarbose tablets) description. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020482s025lbl.pdf. [Accessed March 20, 2014].

      ,
      • Saenz A.
      • Fernandez-Esteban I.
      • Mataix A.
      • et al.
      Metformin monotherapy for type 2 diabetes mellitus.
      ], we, therefore, assume that patients taking both drugs have the similar frequency of doctor visits. Thus, we assume that the relevant costs in treating T2DM, such as doctor visit, diagnostic, inspection, and hospitalization cost, and so forth [
      Chinese Group for Pharmacoeconomic Evaluations Guidelines
      China guidelines for pharmacoeconomic evaluations.
      ], can be set to be equivalent and not included in this study. All costs were based on 2014 prices and expressed in Renminbi (¥). No cost discounting was applied because all costs were measured by a period of 1 year.

       Base-Case Identification

      There is no fixed dosage regimen for the management of hyperglycemia in patients with T2DM with metformin or acarbose or any other pharmacologic agents [

      Glucophage® (metformin hydrochloride tablets) Glucophage® XR (metformin hydrochloride extended-release tablets) description. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020357s031,021202s016lbl.pdf. [Accessed March 20, 2014].

      ,

      Precose® (acarbose tablets) description. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020482s025lbl.pdf. [Accessed March 20, 2014].

      ]. Data on medication use and average dosage were derived from the direct comparison section of the meta-analysis [

      Gu SY, Xu XC, Shi LZ, et al. Cost minimization analysis of clinical option scenarios for metformin and acarbose in treatment of type 2 diabetes: based on direct and indirect treatment comparison results: ISPOR 6th Asia-Pacific Conference. Available from: http://www.ispor.org/research_pdfs/47/pdffiles/PDB27.pdf. [Accessed March 14, 2015].

      ,
      • Chen L.L.
      • Zheng J.
      Comparison of the effect of acarbose, metformin and glipizide on newly diagnosed young type 2 diabetic patients.
      ,
      • Chou W.Z.
      Clinical observation of type 2 diabetes treatment with acarbose.
      ,
      • Hong F.
      The analysis of efficacy and medication of several drugs to treat type 2 diabetes.
      ,
      • Tang Y.
      • Chen F.M.
      The analysis of efficacy and side effects of acarbose and metformin to treat type 2 diabetes.
      ,
      • Wang H.B.
      • Deng X.C.
      • Feng Y.T.
      Clinical observation of diabetes II treatment with acarbose and metformin.
      ,
      • Yang H.L.
      Observation of clinical effect on acarbose to treat type 2 diabetes.
      ,
      • Zhang M.H.
      Treatment effect of metformin and acarbose in patients with type 2 diabetic insulin resistance.
      ,
      • Zhu Z.L.
      • Qiu X.C.
      • Zhu H.P.
      • et al.
      Application of acarbose combined with metformin in treatment of newly diagnosed type 2 diabetes patients.
      ], which directly compared the treatment effect of metformin and acarbose and showed their comparable efficacy in the Chinese population (1500 mg/d for metformin and 150 mg/d for acarbose).

       Sensitivity Analysis

      Because physicians’ compliance with drug’s instruction recommendations or national guidelines with regard to the initiation and monitoring of drug dosage in treating T2DM is unknown, in sensitivity analysis, several different clinical scenarios were developed after interviews with physicians treating diabetic patients, to illustrate potential clinical situations as well as to analyze the difference in annual average treatment costs with metformin and acarbose.
      Based on physicians’ prescribing behaviors in China and the potential increased risk for elevated serum transaminases in patients with low body weight [

      Precose® (acarbose tablets) description. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020482s025lbl.pdf. [Accessed March 20, 2014].

      ], the usual maximum dose of acarbose is slightly different in different weight groups (150 mg/d for weight ≤ 60 kg and 300 mg/d for weight > 60 kg) [

      Diabetes treatments. 2014. Available from: media.empr.com/documents/2/endo_dt_2pt-5_1127.pdf. [Accessed February 25, 2014]

      ,
      • Rodier M.
      • Richard J.L.
      • Monnier L.
      • et al.
      Effect of long term acarbose (Bay g 5421) therapy on metabolic control of non insulin dependent (type II) diabetes mellitus.
      ,
      • Ahr H.J.
      • Boberg M.
      • Krause H.P.
      • et al.
      Pharmacokinetics of acarbose, part I: absorption, concentration in plasma, metabolism and excretion after single administration of [14C] acarbose to rats, dogs and man.
      ]. Meanwhile, because of the difference in clinical prescribing habits and cognition of physicians in China, metformin also has two usual maximum doses (1500 and 2000 mg/d) in clinical practice, which is not strongly associated with patients’ weight. Eight clinical scenarios, therefore, were developed according to different therapeutic regimens for patients with T2DM with different body weights to model different clinical conditions that may reflect real-world usage patterns of patients with T2DM. Scenario 1 considered all patients treated using only one oral drug (metformin or acarbose) at the initial dose. Scenarios 2, 5, and 6 involved patients who received only one oral drug (metformin or acarbose) at the usual maximum dose. Scenarios 3, 4, 7, and 8 simulated a situation that both drugs were titrated from the initial dose to the usual maximum dose gradually in patients with different body weights (Table 1). The common characteristics of scenarios 2 to 4 are that patients’ weight is 60 kg or less and that of scenarios 5 to 8 is that patients’ weight is more than 60 kg. Moreover, scenario 1 includes both weight groups (Table 1).
      Table 1Clinical scenarios for patients with T2DM with different body weight.
      ScenarioPatientDescription
      1All weightsMetformin is maintained in initial dose (500 mg/d); acarbose is maintained in initial dose (50 mg/d).
      2Weight ≤ 60 kgMetformin is maintained in usual maximum dose (2000 mg/d, given in divided doses); acarbose is maintained in usual maximum dose (150 mg/d, given in divided doses).
      3Weight ≤ 60 kgMetformin is started at 500 mg/d for the first week and titrated up to 1000 mg/d given in divided doses in the second week and to 1500 mg/d given in divided doses from the third week onwards.
      Acarbose is started from 50 mg/d during the first week and titrated up to 100 mg/d given in divided doses in the second week and to 150 mg/d given in divided doses from the third week onwards.
      4Weight ≤ 60 kgMetformin is started at 500 mg/d for the first week and titrated up to 1000 mg/d given in divided doses in the second week, to 1500 mg/d given in divided doses in the third week, and to 2000 mg/d given in divided doses from the fourth week onwards.
      Acarbose is started from 50 mg/d during the first week and titrated up to 100 mg/d given in divided doses in the second week and to 150 mg/d given in divided doses from the third week onwards.
      5Weight > 60 kgMetformin is maintained in usual maximum dose (1500 mg/d, given in divided doses); acarbose is maintained in usual maximum dose (300 mg/d, given in divided doses).
      6Weight > 60kgMetformin is maintained in usual maximum dose (2000 mg/d, given in divided doses); acarbose is maintained in usual maximum dose (300 mg/d, given in divided doses).
      7Weight > 60kgMetformin is started at 500 mg/d for the first week and titrated up to 1000 mg/d given in divided doses in the second week and to 1500 mg/d given in divided doses from the third week onwards.
      Acarbose is started from 50 mg/d during the first week and titrated up to 100 mg/d given in divided doses in the second week, to 150 mg/d given in divided doses in the third week, and to 300 mg/d from the fourth week onwards.
      8Weight > 60 kgMetformin is started at 500 mg/d for the first week and titrated up to 1000 mg/d given in divided doses in the second week, to 1500 mg/d given in divided doses in the third week, and to 2000 mg/d given in divided doses from the fourth week onwards.
      Acarbose is started from 50 mg/d during the first week and titrated up to 100 mg/d given in divided doses in the second week, to 150 mg/d given in divided doses in the third week, and to 300 mg/d from the fourth week onwards.
      T2DM, type 2 diabetes mellitus.

      Results

       Annual Average Treatment Cost of Metformin and Acarbose at Base Case

      In base-case cost analysis, the annual treatment cost of metformin was ¥1358.90 while that of acarbose was ¥2260.08 when referring to the lowest price; the annual treatment cost of metformin and acarbose was ¥1598.70 and ¥2708.30 referring to the highest price, respectively. Under the same level of glycemic control, metformin could achieve annual cost savings by 39.87% (lowest price) or 40.97% (highest price) compared with acarbose (Table 2).
      Table 2The annual treatment cost of metformin and acarbose in patients with T2DM.
      ScenarioPrice
      Lowest, the lowest set by market; highest, the highest price set by government.
      Annual treatment cost (¥)Cost difference (¥)
      Cost difference = annual cost of acarbose − annual cost of metformin.
      Saving in annual cost (%)
      Saving in annual cost = (annual cost of acarbose − annual cost of metformin) × 100/annual cost of acarbose.
      AcarboseMetformin
      Base caseLowest2260.081358.90901.1839.87
      Highest2708.301598.701109.640.97
      Patients with T2DM with weight ≤ 60 kg
      Scenario 1Lowest753.36452.97300.3939.87
      Highest902.77532.90369.8740.97
      Scenario 2Lowest2260.081811.86448.2219.83
      Highest2708.302131.60576.721.29
      Scenario 3Lowest2216.741332.83883.9139.87
      Highest2656.361568.041088.3240.97
      Scenario 4Lowest2216.741759.7445720.62
      Highest2656.362070.28586.0822.06
      Patients with T2DM with weight > 60 kg
      Scenario 1Lowest753.36452.97300.3939.87
      Highest902.77532.90369.8740.97
      Scenario 5Lowest4520.161358.903161.2669.94
      Highest5416.601598.703817.970.49
      Scenario 6Lowest4520.161811.862708.359.92
      Highest5416.602131.60328560.65
      Scenario 7Lowest4346.781332.833013.9569.34
      Highest5208.841568.043640.869.90
      Scenario 8Lowest4346.781759.742587.0459.52
      Highest5208.842070.283138.5660.25
      T2DM, type 2 diabetes mellitus.
      low asterisk Lowest, the lowest set by market; highest, the highest price set by government.
      Cost difference = annual cost of acarbose − annual cost of metformin.
      Saving in annual cost = (annual cost of acarbose − annual cost of metformin) × 100/annual cost of acarbose.

       Annual Average Treatment Cost of Metformin and Acarbose at Different Scenarios

      The annual treatment cost of metformin ranged from ¥452.97 to ¥2131.60 whereas that of acarbose ranged from ¥753.36 to ¥2708.30 at the four different scenarios (scenarios 1–4) in which patients’ weight is 60 kg or less. Under these assumptions, metformin also minimizes the cost in all the four scenarios regardless of changes in daily dosage or medication cost, remaining a cost-saving strategy of 19.83% to 40.97% (Table 2).
      The annual treatment cost of metformin ranged from ¥452.97 to ¥2131.60 whereas that of acarbose ranged from ¥753.36 to ¥5416.60 at the five different scenarios (scenario 1, and 5–8) in which patients’ weight is more than 60 kg. For all the five scenarios, metformin administration was the lower cost strategy compared with acarbose, for which savings ranged from 39.87% to 70.49% (Table 2).

      Discussion

      Economic evaluation refers to the comparative analysis of alternative projects in terms of their costs and consequences by using principles and methods of economics. In the context of current health policy, with more and more governments trying to limit the escalation in health expenditure, there is an increasing need to find medical treatment strategies that are as effective but less costly. A pharmacoeconomic approach is commonly used to evaluate the health benefit of drug treatments to gain good value for money. Economic evaluation of medical products is particularly important in a country such as China, where for the inclusion of a drug in the national essential drugs list, the call in and out of a drug in the National Reimbursement Drug List, and the pricing of new drugs, patent medicines, and other drugs, it is now, by law, recommended that technical evaluation for the drugs be conducted by using evidence-based medicine and pharmacoeconomics approaches [

      National Health and Family Planning Commission of the People’s Republic of China. On the issuance of “Administration measures for the national essential medicines list (Provisional)” notice. 2009. Available from: http://www.sda.gov.cn/WS01/CL0056/40754.html. [Accessed March 10, 2014]

      ,

      The Central People’s Government of the People’s Republic of China. The work program for the adjustment of national basic medical insurance, work-related injury insurance and maternity insurance drug lists. 2009. Available from: http://www.gov.cn/gzdt/2009-07/31/content_1380699.htm. [Accessed March 10, 2014]

      ,

      The Central People’s Government of the People’s Republic of China. Opinions on deepening the medical and health system reform. 2009. Available from: http://www.sda.gov.cn/WS01/CL0611/41193_5.html. [Accessed March 10, 2014]

      ,

      National Development and Reform Commission. The measures for the administration of drug price (exposure draft). 2010. Available from: http://www.ypzbxx.com/thread-12092-1-1.html. [Accessed March 10, 2014]

      ].
      This study examined the costs of metformin and acarbose in the treatment of patients with T2DM. We used the cost-minimization analysis technique under the hypotheses that key clinical outcomes and adverse effects of both drugs are effectively equivalent based on results from a previous meta-analysis study [

      Gu SY, Xu XC, Shi LZ, et al. Cost minimization analysis of clinical option scenarios for metformin and acarbose in treatment of type 2 diabetes: based on direct and indirect treatment comparison results: ISPOR 6th Asia-Pacific Conference. Available from: http://www.ispor.org/research_pdfs/47/pdffiles/PDB27.pdf. [Accessed March 14, 2015].

      ]. Our results show that metformin seems to be more cost-effective than acarbose.
      In economic evaluation, it is difficult to accurately measure the study variables, and each medication therapy may bring different treatment costs when applied among different population or medical institutions; therefore, it is important to verify the effect of basic assumptions on study results. Thus, we developed eight scenarios, in sensitivity analyses, to mirror the real-life cost profile. The results are consistent with the base-case analysis, corroborating that metformin is more cost-effective than acarbose. Our results, however, may represent a cost-effective advantage for metformin only if differences in dosage adjustment and monitoring were observed in a real clinical practice and underlying hypotheses mentioned above are true.
      Results from this study confirm findings from several economic evaluation studies conducted in China, comparing metformin monotherapy with acarbose monotherapy in the treatment of T2DM. The studies reported that metformin was cost-effective than acarbose for treating T2DM [
      • Bu Y.S.
      • Qu S.
      • Liu W.
      • et al.
      Economic evaluation of two different oral drug treatments for type 2 diabetes.
      ,
      • Shen W.X.
      • Zhang B.S.
      Cost-effectiveness analysis of four treatment therapies for type 2 diabetes.
      ,
      • Guo S.Y.
      • Tan M.X.
      Cost-effectiveness analysis of drugs in treatment of type 2 diabetes mellitus.
      ,
      • Lin L.
      • Ge Y.P.
      Cost-effectiveness analysis for three common treatments for type 2 diabetes.
      ,
      • Ji B.
      • Liu S.
      The cost-effectiveness analysis of oral hypoglycemic drugs in the treatment of type 2 diabetes mellitus.
      ,
      • Zhang Q.X.
      • Liu Y.X.
      Cost-effectiveness analysis of three drug treatments for type 2 diabetes mellitus.
      ,
      • Wu S.J.
      • Wu W.
      ], and particularly, it was superior to acarbose in controlling fasting blood glucose [
      • Wang W.D.
      The cost-effectiveness analysis of five medications for type 2 diabetes.
      ,
      • Cai X.L.
      • Huang L.
      • Zhao R.
      • et al.
      Analysis on pharmaceutical economics of different oral antidiabetic drugs for treating type-2 diabetes mellitus.
      ,
      • Zheng Y.Y.
      Cost-effectiveness analysis of 3 different drugs in the treatment of type 2 diabetes mellitus.
      ,
      • Zhou X.
      • Yao Z.J.
      • Tian X.Y.
      The cost-effectiveness analysis of three treatments for type 2 diabetes.
      ,
      • Xu W.Z.
      ]. As the course of T2DM prolongs, any single therapy may find it difficult to effectively control the blood glucose level of patients with T2DM, and then there is a need to use combination therapies to strengthen glycemic control in clinical practice. In this context, several studies assessing the comparative efficacy and cost of metformin and acarbose from the perspective of drug combination also indicate that metformin combination therapy is still a preferable therapeutic regimen compared with acarbose combination therapy [
      • He Z.G.
      • Ding Q.F.
      • Jin L.
      Comparison of cost-minimization analyses between metformin and acarbose combined with insulin in treating type 2 diabetes mellitus.
      ,
      • Wang J.Y.
      Cost-effectiveness analysis of commonly used hypoglycemic drug combination regimens for the treatment of type 2 diabetes.
      ,
      • Xue X.
      • Gao J.R.
      • Xia L.Z.
      • et al.
      Cost-effectiveness analysis of glimepiride combined with different drugs in treatment of type 2 diabetes mellitus.
      ,
      • Sun K.
      ]. Nevertheless, the reliability of these evaluation results might be constrained attributable to small sample sizes (range 87–705) in their basal clinical trials; thus, these findings should be considered with caution. Furthermore, a review of the economic evaluation of metformin hydrochloride and acarbose suggests that they have a similar role in prolonging the life of patients, improving the cardiovascular disease, and preventing or delaying the onset of T2DM [
      • Lu Z.Q.
      • Ding W.
      Economic evaluation of metformin hydrochloride and acarbose on treating type 2 diabetes mellitus.
      ]. Metformin hydrochloride is a preferred treatment for patients with T2DM, with a higher efficiency in reducing fasting blood glucose and minimum cost compared with other hypoglycemic drugs. Although acarbose is good at reducing postprandial blood glucose, it has a higher cost [
      • Lu Z.Q.
      • Ding W.
      Economic evaluation of metformin hydrochloride and acarbose on treating type 2 diabetes mellitus.
      ]. Moreover, in patients with impaired glucose tolerance, metformin demonstrates a better value for money [
      • Lu Z.Q.
      • Ding W.
      Economic evaluation of metformin hydrochloride and acarbose on treating type 2 diabetes mellitus.
      ]. Metformin is more cost-effective not only in treating T2DM but also in preventing the onset of diabetes compared with acarbose [
      • Hu Y.
      • Chen S.Y.
      • Wang J.Y.
      Cost-effective analysis of preventive treatment on diabetes.
      ,
      • Zhang H.R.
      Comparison of efficacy and costs of acarbose and metformin hydrochloride in treating for patients with impaired glucose tolerance.
      ].
      This study was conducted from a payer’s perspective, and the indirect cost related to the T2DM treatment was not taken into account. Direct medical costs theoretically consist of fees for doctor visit, medication cost, diagnostic cost, inspection cost, hospitalization cost, transport cost, and so forth [
      Chinese Group for Pharmacoeconomic Evaluations Guidelines
      China guidelines for pharmacoeconomic evaluations.
      ]. However, in this study, we estimated only the drug cost, not other costs because we assumed that other costs are the same in the two treatment groups. This study, furthermore, considers only a single monotherapy for 1 year; however, in clinical practice, because of the complexity of diabetes, drug combination therapy is common and patients may switch drugs, which can have an impact on the cost; over a longer period, more complications related to diabetes, including microvascular and macrovascular disease, may occur [
      American Diabetes Association
      Standards of medical care in diabetes--2013.
      ], which can also add treatment costs. Thus, more studies are needed to understand the comprehensive annual costs to provide disease burden information for guiding decision making of resource allocation.
      Regardless of these limitations, our study has a noteworthy strength that it is the first economic evaluation focusing on the comparison of metformin with acarbose in T2DM treatment, which is conducted on the basis of results from a meta-analysis study with large sample sizes and adequate clinical data.

      Conclusions

      Metformin appears to provide better value for money than does acarbose. Findings from this study are consistent with previous studies that metformin is undoubtedly the first choice in the management of T2DM, with significantly glucose-lowering effects and low treatment costs.

      Acknowledgments

      Bristol-Myers Squibb sponsored this study.
      Source of financial support: These findings are the result of work sponsored by Bristol-Myers Squibb, Shanghai, China. The views expressed in this article are those of the authors.

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