The American Journal of Managed Care July 2008
Self-monitoring of Blood Glucose Levels in Patients With Type 2 Diabetes Mellitus Not Taking Insulin: A Meta-analysis
Objective: To perform a meta-analysis of randomized controlled trials (RCTs) and systematic reviews evaluating the efficacy of self-monitoring of blood glucose (SMBG) levels among patients with diabetes mellitus (DM).
Study Design: Meta-analysis of RCTs among patients with DM not taking insulin comparing patients with SMBG versus those without SMBG and reporting results as change in glycosylated hemoglobin (A1C) values.
Methods: Prior systematic reviews and a PubMed search were used to identify studies. Data were extracted by trained physician reviewers working in duplicate. Trials were classified according to duration of the intervention, and random-effects meta-analysis was used to pool results.
Results: Three trials of SMBG of 3 months’ duration were too heterogeneous to pool. Nine other trials were identified. Five trials of SMBG of 6 months’ duration yielded a pooled effect estimate of a decrease in mean A1C values of -0.21% (95% confidence interval [CI], -0.38% to -0.04%). Four trials that reported outcomes of 1 year or longer yielded a pooled effect estimate of a decrease in mean A1C values of -0.16% (95% CI, -0.38% to 0.05%). Three trials reported hypogly- cemic outcomes, which were increased in the patients using SMBG, although this mostly involved asymptomatic or mild episodes.
Conclusions: At most, SMBG produces a statistically significant but clinically modest effect in controlling blood glucose levels in patients with DM not taking insulin. It is of questionable value in helping meet target values of glucose control.
(Am J Manag Care. 2008;14(7):468-475)
Self-monitoring of blood glucose (SMBG) levels is proven effective at helping control glucose levels in patients with diabetes mellitus (DM) taking insulin. The usefulness of SMBG in patients with DM not taking insulin is unclear.
Our meta-analysis of 9 randomized controlled trials of SMBG found a statistically significant improvement in glycosylated hemoglobin outcomes at 6 months of -0.21%. Results at 3 months or 12 months were not significant.
At best, SMBG is an intervention of modest efficacy in patients with DM not taking insulin.According to the World Health Organization,1 at least 180 million people worldwide have diabetes mellitus (DM). The National Diabetes Information Clearinghouse estimates that DM costs $132 billion in the United States every year.2 Given these estimates along with the projection that the worldwide incidence of DM will double in the next 20 years,1 research into better management of this chronic disease is important.
Glucose control along with blood pressure and lipid control is a main goal of DM management. In addition to pharmaceutical agents, an advocated method to achieve better glucose control is self-monitoring of blood glucose (SMBG) levels. For patients with DM taking insulin, SMBG has generally been accepted as necessary to help monitor the effect of insulin on daily blood glucose levels, with adjustments in dosage made in response to SMBG values. However, evidence supporting the use of SMBG for patients with DM not requiring insulin is not as clear. Self-monitoring of blood glucose levels is postulated to have a beneficial effect on glucose levels in patients not taking insulin by promoting dietary and lifestyle changes that a patient may make as a response to feedback provided by blood glucose results.3-6
Prior trials and systematic reviews have reached conflicting results, with 6 trials4,5,7-10 and 3 reviews11-13 reporting benefits and 3 trials3,6,14 and 3 reviews 15-17 reporting no benefits. With an estimated cost of $466 million for Medicare alone, establishing the efficacy or lack of efficacy of SMBG represents an important goal for providers and payers interested in optimizing management of this condition. Because new larger and better-quality trials of SMBG continue to appear, we undertook a metaanalysis to provide the best current estimate of the efficacy of SMBG in patients with type 2 DM not taking insulin.
We first identified prior systematic reviews and meta-analyses on this topic. We identified 6 reviews.11-13,15-17 We judged the search strategy and inclusion and exclusion criteria of the review by Welschen et al,12 which included studies published from 1996 to September 2004, to be comprehensive and acceptable as the basis to begin our review. We updated this review by searching PubMed from the end date of the prior search to July 2007. We searched PubMed for the following terms: randomized controlled trial AND diabetes mellitus, as well as type 2 AND blood glucose self-monitoring. In addition to our PubMed search and screening of references from prior reviews, we performed reference mining of retrieved articles and received articles from experts. During this process, another review13 became available, and we reference mined this review as well.
Two trained researchers (AT, MR), both general internists with a special interest in DM, reviewed the list of titles and selected articles for further review. Each article retrieved was reviewed using a brief screening form. To be included in our analysis, a study had to measure the efficacy of SMBG alone or as part of a multicomponent intervention, measure glycosylated hemoglobin (A1C) level as an outcome, and have a follow-up duration of 12 weeks or longer. Eligible study designs included randomized controlled trials (RCTs) and controlled clinical trials. Observational studies, case reports, nonsystematic reviews, letters to the editor, and other similar contributions were excluded. Systematic reviews were reference mined.
Data were independently abstracted by 2 general internists (AT, MR) trained in critical reading of the literature, with consensus resolution. The following data were abstracted from included trials: design; randomization and appropriateness; blinding and appropriateness; withdrawals and dropouts described; sample size enrolled and followed up; characteristics of the population, including percentage of women and race/ethnicity; mean, median, and range of ages; body mass index and duration of DM; reported comorbidities; sample size, intervention, and exposure data for each arm of the study (intervention and exposure data included components of the intervention, total number of visits, frequency of SMBG, number of days per week monitored, duration of treatment, and cotherapies); outcomes measured; intervals in which the outcomes were measured; and adverse events.
The mean (SD) A1C level was recorded by treatment arm for each reported follow-up point. For trials that reported a mean outcome but no standard deviation, we estimated the standard deviation by taking the weighted mean standard deviation across all other trials that reported standard deviations for the A1C level.18
To assess internal validity of the eligible trials, we used the Delphi list.19 We abstracted data on treatment allocation; method of randomization; similarity at baseline regarding the most important prognostic indicators; specified eligibility criteria; blinding of outcome assessor, care provider, and patient; presentation of point estimates and measures of variability; and intent-to-treat analysis. Work performed by the Cochrane Collaboration Back Review Group supports these items individually as being associated with bias and the use of a threshold of half the items for distinguishing “high-quality” versus “low-quality” studies (M. Suttorp, MS, written communication, 2006).
We synthesized data among the articles that were determined to be clinically eligible. Duration of follow-up and frequency of SMBG were reviewed across studies to see if they were comparable.
Since the outcome of interest was the same across all trials, a mean difference was calculated for each time point that reported statistical data. The mean difference is the difference between the follow-up mean A1C level for the SMBG group and the follow-up mean A1C level for the control group. A negative mean difference indicates that the SMBG group has a lower mean A1C score than the control group. For our main analysis, we did not control for the baseline mean A1C level for each group (a difference of differences estimate) because there is evidence that this approach is susceptible to bias.20 We present results controlling for the baseline as a sensitivity analysis.
A pooled estimate was calculated by follow-up duration in the following categories: 3 to 6 months, 6 to 11 months, and 12 months or longer. The pooled estimate was calculated using the DerSimonian and Laird21 random-effects model. In addition, we calculated a pooled estimate stratified by highquality and low-quality trials.
Meta-regression analyses22 were performed to individually examine the effect of treatment frequency, quality score, and mean baseline A1C level on the mean difference. For trials with more than 1 follow-up duration, the long-term estimates were used.
Test of heterogeneity was performed using the I2 statistic.23 I2 values close to 100% represent very high degrees of heterogeneity. Publication bias was examined using Begg rank correlation24 and Egger regression asymmetry test.25 All analyses were conducted in STATA 9 (Stata Corp LP, College Station, Texas).26
In total, we examined 55 titles. Seventeen titles were identified from prior systematic reviews. The electronic update search identified 25 titles. An additional 12 titles were identified through reference mining. One was identified by a content expert (JEW). Of the titles identified through our electronic literature search, 14 were rejected as irrelevant to the project. This left 41 from all sources. Eleven articles were excluded at abstract review.
In total, we reviewed 30 articles. Initial screening of the articles resulted in 16 RCTs that measured the effect of SMBG with at least 3 months of follow-up. Seven were excluded, 1 because the trial presented duplicate data, 2 because they did not report A1C levels as an outcome, 1 because the trial included an unknown number of patients taking insulin, and the other 3 because the trials compared a control group of patients with SMBG versus an intervention group of patients with SMBG plus other components (Figure 1).
Description of the Evidence
The 9 RCTs ranged in size from 29 to 988 subjects. All patients had type 2 DM, with mean durations of 3 to 13 years. All trials but 1 included only patients treated without insulin.
The mean ages of patients ranged from 50 to 66 years. Almost all trials included counseling and education with SMBG in the intervention group, but other components of the intervention varied (Table 1). All trials measured A1C level as an outcome; 5 trials assessed this at 6 months, and 4 trials assessed this at 1 year or later. Three other trials assessed this at 3 months but were too heterogeneous to pool. The quality of trials varied; most trials scored positively on less than half of the criteria on the Delphi list.19 Details of each trial are given in Table 2 (quality criteria are available in an online table [eAppendix Table; available at www.ajmc.com]).
Improving Glycemic Control
We grouped trials based on the duration of the intervention. The individual and pooled results are shown in Figure 2.
We identified 3 trials6,9,27 that reported A1C outcomes at 3 months. The trials reported variable results. We did not pool the results of these 3 trials because their results were too heterogeneous, with an I2 statistic of 67%. We identified 5 trials3-5,14,27 that reported outcomes at 6 months. One trial4 reported a statistically significant improvement in A1C level, although a second trial 5 yielded a statistically significant result after adjusting for baseline differences. The random-effects pooled effect estimate of these 5 trials was a change in mean A1C values of -0.21% (95% confidence interval [CI], -0.38% to -0.04%). The I2 statistic for heterogeneity was 0%.
We identified 4 trials6-8,27 that reported outcomes at 1 year or longer. No study reported a statistically significant difference between groups in the mean A1C values, although one study 7 reported statistically significant benefits after adjusting for baseline differences in A1C values. The randomeffects pooled effect estimate of these 4 trials was a change in mean A1C values of -0.16% (95% CI, -0.38% to 0.05%). The I2 statistic for heterogeneity was 0%.
We performed several additional analyses. We compared studies scoring 5 or more Delphi items positively (which we called high quality) with those scoring fewer than 5 items positively (low quality). The pooled results showed no statistically significant differences between high-quality and low-quality studies.