|
The clinical effectiveness and cost-effectiveness of pioglitazone for type 2 diabetes mellitus: a rapid and systematic review |
Chilcott J, Wight J, Lloyd Jones M, Tappenden P |
|
|
Authors' objectives To evaluate the incremental clinical and cost-effectiveness of pioglitazone in its licenced indication (UK product licence), in combination with insulin, and as monotherapy (unlicensed indications). The licensed indication specifies the following:
'only in oral combination treatment of type 2 diabetes mellitus in patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or a sulphonylurea';
'in combination with metformin only in obese patients';
'in combination with a sulphonylurea only in patients who show intolerance to metformin or for whom metformin is contraindicated'.
Searching MEDLINE, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, DARE, NHS EED, and HEED were searched using keyword strategies. Most searches were performed in June 2000 but the MEDLINE search was updated in August 2000. Further sources, including industry submissions, were handsearched.
Study selection Study designs of evaluations included in the reviewSystematic reviews, randomised controlled trials (RCTs) and economic evaluations were to be included in the review.
Specific interventions included in the reviewPioglitazone alone or in combination with other antidiabetic agents. Studies of these compared with placebo or other agents were eligible for inclusion. In the included studies, pioglitazone was used as monotherapy (7.5 to 45 mg/day) and in combination with sulphonylurea (15 to 45 mg/day), metformin (30mg/day) and insulin (30 mg/day).
Participants included in the reviewPatients with type 2 diabetes mellitus.
Outcomes assessed in the reviewAt least one of the following outcomes was assessed: glycaemic control (blood glucose or glycosylated haemoglobin); cardiovascular risk factors (lipids and weight); pyruvate kinase; adverse events. Some of the included studies also measured insulin C peptide, blood insulin, blood C-reactive protein, rates of change of blood glucose, hepatic glucose production, and total glucose disposal.
How were decisions on the relevance of primary studies made?The studies were assessed with reference to specified inclusion criteria. The authors do not state how many of the reviewers selected the studies for the review, or whether there was any independent checking of the decisions.
Assessment of study quality The quality of the included studies was assessed using the standard checklist of Jadad et al. (see Other Publications of Related Interest). The authors do not state how many of the reviewers performed the quality assessment, or whether there was any independent checking of the decisions.
Data extraction Two reviewers extracted the data using customised data extraction forms. The following categories of data were extracted: study name; country; year; source of report; comparison studied; study design; patient details; treatment groups and numbers randomised; study procedure; outcome measures reported; and results.
Methods of synthesis How were the studies combined?A formal meta-analysis of either the monotherapy or the combination therapy studies was not possible due to the high degree of clinical diversity between the studies, in terms of their duration and the different drug combinations used. A narrative synthesis was therefore undertaken.
How were differences between studies investigated?The narrative synthesis was divided into monotherapy and combination therapy results, with subdivisions according to the outcome measure.
Results of the review Eleven RCTs (over 3,000 patients) were included in the review; one study did not report the sample size.
In both monotherapy and combination therapy, pioglitazone appeared to be effective in reducing blood glucose in patients with poorly controlled type 2 diabetes. When used in combination with metformin, sulphonylurea or insulin, pioglitazone (15 or 30 mg/day) led to a significant fall in blood glucose and glycosylated haemoglobin; a greater effect was observed at the higher dose. Monotherapy and combination therapy studies also demonstrated a fall in triglyceride levels, and an increase in high-density lipoprotein cholesterol levels, when the doses of pioglitazone were at least 30 mg. Pioglitazone treatment was associated with significant weight gain in the short term and for up to one year. There was no direct evidence available on the effect of pioglitazone on diabetic complications, including cardiovascular mortality.
Authors' conclusions The evidence suggested that, compared with placebo, pioglitazone was effective in reducing blood glucose in patients with inadequate glyceric control, both when used as monotherapy and in combination with existing licenced therapies. However, there was no firm evidence to indicate that pioglitazone was more effective than any other antidiabetic agent, particularly when used in combination. In addition, it was unclear how pioglitazone therapy affected the incidence of microvascular and cardiovascular complications.
CRD commentary This systematic review had a clear objective and well-defined inclusion criteria, in terms of the study design, participants, indication and outcomes. However, the review did not confine itself to the original review question but addressed broader questions regarding the efficacy and safety of pioglitazone. The search for literature was comprehensive with no date or language restrictions.
Confidential information provided to the authors by the manufacturers of pioglitazone could not be included in the review. The review did not provide details of the number of reviewers who performed the review, the methods used, or whether there was any independent assessment or checking. The quality of the included RCTs was assessed using a validated checklist and was found to be good. The review presented a good level of individual study details, both in the tables and in the text. The narrative synthesis adopted by the authors was appropriate given the clinical diversity of the studies in the review. Although the studies were described by the various outcomes reported, a synthesis of the findings was only presented for a few of these. A more detailed synthesis would have been helpful. Generally, this was a well-conducted review and the authors' conclusions are supported by the evidence presented.
Implications of the review for practice and research Practice: The authors state 'there is no firm evidence to indicate that pioglitazone is more effective than any other antidiabetic agent particularly when used in combination'.
Research: The authors state that further evidence is needed regarding the following.
'The clinical effectiveness and cost-effectiveness of pioglitazone in combination therapy compared with other possible combination therapies (e.g. rosiglitazone in combination, or sulphonylurea plus metformin, or insulin with or without an oral antidiabetic agent.'
'Whether or not the risk of microvascular complications is reduced by the improved glyceric control achieved using pioglitazone.'
'Whether or not risk of cardiovascular events is reduced by the changes in lipid levels achieved using pioglitazone.'
Funding NHS R&D Health Technology Assessment (HTA) Programme, project number 00/06/01.
Bibliographic details Chilcott J, Wight J, Lloyd Jones M, Tappenden P. The clinical effectiveness and cost-effectiveness of pioglitazone for type 2 diabetes mellitus: a rapid and systematic review. Health Technology Assessment 2001; 5(19): 1-71 Other publications of related interest Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12.
Indexing Status Subject indexing assigned by NLM MeSH Cost-Benefit Analysis; Diabetes Mellitus, Type 2 /drug therapy; Drug Therapy, Combination; Humans; Hypoglycemic Agents /economics /therapeutic use; Thiazoles /economics /therapeutic use; Thiazolidinediones AccessionNumber 12001008399 Date bibliographic record published 30/09/2002 Date abstract record published 30/09/2002 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
|
|
|