|Insulin glargine in combination with oral antidiabetic drugs as a cost-equivalent alternative to conventional insulin therapy in type 2 diabetes mellitus
|Lechleitner M, Roden M, Haehling E, Mueller M
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
The use of insulin glargine (IG) in combination with oral antidiabetic drugs (OADs) for the treatment of patients with Type 2 diabetes mellitus.
Economic study type
The study population comprised patients with Type 2 diabetes mellitus not adequately controlled by OADs.
The setting was primary care. The economic study was carried out in Austria.
Dates to which data relate
The effectiveness and resource use data were gathered from May to October 2004. The price year was not reported.
Source of effectiveness data
The effectiveness evidence was derived from a single study.
Link between effectiveness and cost data
The costing was carried out prospectively on the same sample of patients as that used in the effectiveness analysis.
Power calculations, if performed, were not reported. The authors stated that it was planned to include a total of 600 patients. The primary analysis compared IG-OAD patients with CIT patients who initiated the respective therapies. However, in order to minimise systematic errors, the authors considered a further historical group of patients, including patients who were currently on conventional therapy (retrolective CIT). A total of 818 patients were identified over the study period and were included in the main analysis. There were 393 patients in the IG-OAD group, 210 patients in the CIT group, and 215 patients in the retrolective CIT group. After applying some non-evaluability criteria (missing dates of visits, no pre-treatment documented, treatment error, treatment duration of less than 61 days, and premature termination of treatment), the study sample consisted of 678 evaluable patients. Of these, 339 were in the IG-OAD group, 138 were in the CIT group, and 201 were in the retrolective group. The mean age of the participants was 63 years in the IG-OAD group and 67.5 years in the CIT group. However, the analysis revealed that the results were similar in the two samples of patients (i.e. before and after application of the non-evaluability criteria). It was not stated whether some patients refused to participate or were excluded for any reason from the study sample.
This was a multi-centred, concurrent, historically controlled, three-arm, cohort study. The patients were identified by 65 investigators in diabetes centres throughout Austria. One case record binder contained space for all three patient groups in a ratio of 6:3:3 (IG-OAD, CIT and retrolective CIT). The length of follow-up was 3 months. The patients were contacted at baseline visits and at an end point visit 12 to 14 weeks after recruitment. No patient was lost to the follow-up assessment. The study participants and investigators were blinded to the objectives of the study but were aware of treatment allocation.
Analysis of effectiveness
The analysis of the clinical study considered all patients included in the initial study sample (n=818), as well as the sub-group of evaluable patients only (n=678). The primary outcome measures were glycaemic control and frequency of adverse events. Glycaemic control was based on changes in fasting blood glucose (FBG) and haemoglobin levels (HbA1c). The study groups were comparable at baseline in terms of their clinical and demographic factors, although there was a non significant trend towards older patients in the CIT group.
The median FBG at baseline was 179 mg/dL (interquartile range, IQR: 150 to 212) in the IG-OAD group and 180 mg/dL (IQR: 159 to 221) in the CIT group. It decreased at final follow-up to 130 mg/dL (IQR: 112 to 150) in the IG-OAD group and 134 mg/dL (IQR: 112 to 143) in the CIT group. An FBG of 155 mg/dL (IQR: 128 to 192 mg/dL) in the retrolective CIT group was reported.
The median HbA1c decreased from baseline values of 8.7% (IQR: 7.8 to 9.9) in the IG-OAD group and 9.2% (IQR: 8.3 to 10.4) in the CIT group to 7.8% (IQR: 7.1 to 8.5) in both groups at end point. The median HbA1c was 8.0% (IQR: 7.2 to 8.9) in the retrolective CIT group.
Differences in clinical outcomes did not reach statistical significance.
Three adverse events were observed over the study period. There was one hypoglycaemic event in the IG-OAD group and one hypoglycaemic event and one case of pneumonia in the CIT group, but treatment was continued in all patients. However, three further CIT patients experienced hypoglycaemia, which led to premature treatment discontinuation.
The effectiveness analysis showed that the two treatments were equally effective and safe.
Measure of benefits used in the economic analysis
No summary benefit measure was used in the economic analysis since the effectiveness analysis showed that the clinical outcomes in the two groups were comparable. In effect, a cost-minimisation analysis was carried out.
The analysis of the costs appears to have been carried out from the perspective of Austrian sickness funds. It included the costs of insulin, OADs, blood glucose test strips and lancets, and needles. The unit costs were presented separately from the quantities of resources used for most items. The costs were estimated from typical Austrian sources. Resource use was based on actual treatment patterns derived from the clinical study. Discounting was not relevant as the costs were incurred during a short time. The price year was not reported.
Statistical analysis of costs
The costs were presented as mean values with confidence intervals. Statistical analyses were carried out to test the statistical significance of cost-differences between the groups.
The indirect costs were not included in the economic analysis.
Sensitivity analyses were not performed.
Estimated benefits used in the economic analysis
See the 'Effectiveness Results' section.
The costs of OADs were higher in the IG-OAD group, whereas the costs of blood glucose test strips and insulin were lower in this group, markedly so for insulin.
Overall, the mean total daily cost per patient was EUR 1.91 in the IG-OAD group, EUR 1.99 in the CIT group, and EUR 2.01 in the retrolective CIT group.
Confidence intervals overlapped between the groups, suggesting that cost-differences were minimal and did not reach statistical significance.
Synthesis of costs and benefits
A synthesis of the costs and benefits was not relevant as a cost-minimisation analysis was performed.
Once-daily insulin glargine (IG) combined with oral antidiabetic drugs (OADs) was as effective in glycaemic control as conventional insulin therapy (CIT) with premixed insulin twice daily, in patients with poorly controlled Type 2 diabetes mellitus in Austria. The lower insulin dosage and the fewer blood glucose test strips among IG patients led to cost-equivalence of the two therapies.
CRD COMMENTARY - Selection of comparators
The rationale for the selection of the comparators was clear. The choice of the two interventions was consistent with the objective of the study. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness
The effectiveness evidence was based on a prospective observational study. The lack of randomisation might have introduced some selection bias. In order to avoid systemic errors, the authors considered a further group of patients, based on historical controls. Data for this historical group were derived from case report forms. Blinding was not performed, but it would presumably have been difficult given the nature of the interventions examined in the study. Power calculations were not performed and no justification for the sample size was provided. Limited information on the sample selection process was reported. The advantages of the study were baseline comparability of the study groups, inclusion of the full sample of patients, use of statistical analyses, and the multi-centred design. The study sample was heterogeneous and appears to have been representative of the patient population. It was unclear whether the length of follow-up was appropriate or whether the use of a longer timeframe would have affected the results of the analysis. These issues should be considered when assessing the internal validity of the study.
Validity of estimate of measure of benefit
No summary benefit measure was used in the analysis as a cost-minimisation analysis was conducted. Please refer to the comments in the 'Validity of estimate of measure of effectiveness' field (above).
Validity of estimate of costs
The costs included appear to have been consistent with the perspective of sickness funds which, although not explicitly reported, might have been the perspective adopted in the analysis. A breakdown of the cost items was given, as was extensive information on resource consumption and unit costs. This enhances the possibility of replicating the analysis in other settings. The sources of the costs were reported. Statistical analyses of the costs were carried out, but the cost estimates were specific to the study setting and the impact of using different costs was not investigated in the sensitivity analysis. Resources were gathered in 2004 but the price year was not reported, which makes reflation exercises in other time periods difficult.
The authors stated that their findings were consistent with those from published clinical trials. The issue of the generalisability of the study results to other settings was not addressed and sensitivity analyses were not carried out. This limits the external validity of the study. The analysis referred to patients with Type 2 diabetes mellitus with poor control of their disease, and this was reflected in the authors' conclusions. The authors noted that one of the strengths of the analysis was the use of a pragmatic study, which reflected real-life conditions.
Implications of the study
The study results support the use of IG combined with OADs for the control of Type 2 diabetes mellitus.
Lechleitner M, Roden M, Haehling E, Mueller M. Insulin glargine in combination with oral antidiabetic drugs as a cost-equivalent alternative to conventional insulin therapy in type 2 diabetes mellitus. Wiener Klinische Wochenschrift 2005; 117(17): 593-598
Other publications of related interest
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321;405-12.
Riddle MC, Rosenstock J, Gerich J. The Treat-To-Target Trial. Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-6.
Fritsche A, Schweitzer MA, Haring HU. Glimepiride combined with morning insulin flargine, bedtime nautral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. Ann Intern Med 2003;138:952-9.
Subject indexing assigned by NLM
Administration, Oral; Austria /epidemiology; Cohort Studies; Cost-Benefit Analysis; Diabetes Mellitus, Type 2 /drug therapy /economics /epidemiology; Drug Combinations; Female; Health Care Costs /statistics & Humans; Hypoglycemic Agents /administration & Incidence; Insulin /administration & Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Therapeutic Equivalency; Treatment Outcome; derivatives /economics; dosage /analogs & dosage /economics; numerical data
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