GDM: Pharmacologic Therapy (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
The purpose of this study was to compare the use of glyburide with insulin for the treatment of gestational diabetes mellitus (GDM) unresponsive to diet therapy.
Inclusion Criteria:

Women with singleton pregnancies who had GDM diagnosed between 12 and 34 weeks between January 1999 and December 2002.

Abnormal glucose load test (GLT) of 140 mg/dL or greater and a diagnostic 3-hour glucose tolerance test (GTT) using National Diabetes Data Group (NDDG) criteria (fasting > 105, 1 hour > 190, 2 hours > 165, 3 hours >  145 mg/dL.

Exclusion Criteria:
Fasting plasma glucose > 140 mg/dL on GTT.
Description of Study Protocol:

Recruitment

Recruited from Kaiser Permanente Northern California Medical Care Program.  2 study groups were identified:

Insulin group (those with GDM diagnosed in 1999-2000)

Glyburide group (those with GDM diagnosed in 2001-2002).

Subgroup of women with GDM diagnosed in 2001-2002 who were treated with insulin not glyburide

Design:  Retrospective Cohort Study 

Blinding used (if applicable):  Not applicable

Intervention (if applicable):  Glyburide or insulin therapy

Statistical Analysis

Student t test was used to evaluate the difference of means, Chi squared test or Fisher exact test where appropriate was used to evaluate the difference in proportions, the nonparametric Wilcoxon 2-sample test was used for interval level variables found not to be normally distributed by the Shapiro-Wilks test at p <0.01. Multivariable logistic regression was used to compute the adjusted odds ratios (ORs) and 95% CIs controlling for variables shown to differ between the insulin and glyburide groups in univariate analyses.

 

Data Collection Summary:

Timing of Measurements

All data collected from review of clinical information databases and charts, KPNC database, and KPNC Neonatal Minimum Data Set. 

Dependent Variables

  • Maternal outcomes of insulin and glyburide groups (Delivery gestational age, method of delivery)
  • Neonatal outcomes of insulin and glyburide groups (Birthweight, number of LGA, SGA, macrosomic, NICU admissions)

Independent Variables

  •  Glyburide therapy
  •  Insulin therapy

Control Variables

  • BMI
  • Ethnicity
  • Gestational age at diagnosis of GDM
  • Degree of glucose tolerance at diagnosis of GDM
Description of Actual Data Sample:

Initial N: 584 women

Attrition (final N): 584

Age: Insulin group 32.1 + 5.2 years, Glyburide group 32.8 + 5.4 years

Ethnicity: (p value 0.001 between groups)

 

Number (%) Insulin Glyburide
White 116 (43) 65 (28)
Hispanic 66 (25) 56 (24)
Black 10 (4) 9 (4)
Asian 64 (24) 88(37)

Other relevant demographics:

There were signficant differences between groups in fasting oral glucose tolerance tests but no signficant differences between groups in the 1, 2 or 3 hour values.

Anthropometrics

Other than the differences in ethnicity in groups there were no other signficant differences.

Location: Kaiser Permanente Northern California Medical Care Program

 

Summary of Results:

 

Maternal and neonatal characteristics

mean   SD

Insulin group

n = 268

Glyburide group

n = 236

P value

Delivery gestaional age (wk)

38.8  1.7 38.7   1.7 0.61

Birthweight (g)

 3599   650

 3661   629

 0.28

LGA no (%)

 63 (24)

 60 (25)

 0.62

Macrosomia no (%)  64 (24)  60 (25)  0.69
Preeclampsia no (%)  16 (6)  28 (12)  0.02
Phototherapy no (%)  12 (5)  21 (9)  0.046
NICU :admission no (%)  65 (24)  35(15)  0.008
NICU: length of stay (d)  4.3   9.6  8. 0   10.1  0.002

 

Other Findings - Comparision of glyburide and insulin groups:  adjusted odds ratio for birth outcomes

 

 

         OR 95 % CI
Preeclampsia 2.32 1.17-4.63
Macrosomia 1.28 0.82- 2.00
LGA 1.44 0.91-2.27
Hyperbilirubinemia 1.18 0.75-1.85
NICU admission 0.57 0.34-0.93
 Phototherapy  2.20  0.99-4.87

Author Conclusion:
In a large managed care organization, glyburide was at least as effective as insulin in achieving glycemic control and similar birth weights in women with GDM who failed diet therapy. The increased risk of preeclampsia and phototherapy in the glyburide group warrant further study.
Funding Source:
University/Hospital: University of Copenhagen (Denmark)
Reviewer Comments:
Large sample size.  Authors note that women receiving glyburide had lower BMIs, lower mean fasting on GTT, and were more likely to be Asian, but they controlled for these variables.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? ???
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? ???
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes