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 neonatal results from patients with gestational diabetes mellitus (GDM) who were treated with insulin, glyburide and acarbose.
Inclusion Criteria:
  • Women diagnosed with GDM who needed therapy in addition to diet and exercise programs.
  • Single gestations 
Exclusion Criteria:
  • Patient choice to stop study
  • Pathology that required faster glucose control such as corticoid therapy.
  • Concommitant pathologies that could effect therapy or perinatal results were also excluded.
Description of Study Protocol:

Recruitment Patients were recruited from the Darcy Vargas Maternity Hospital

Design:  Randomized Clinical Trial.  Patients were randomized into three groups - conventional therapy (insulin), glyburide, and acarbose

Blinding used (if applicable):  not possible

Intervention (if applicable)

Initial insulin therapy was dosed based on patient's weight and gestational age (0.7 IU/kg in the first, 0.8 IU/kg in the second and 0.9 IU/kg in the third trimester). Regular insulin was given before main meals and NPH given at bed times in equal doses.

Glyburide dosing was: 5 mg q AM initially, increasing every 7 days until reaching glucose control with a maxium dose of 20 mg/day.

Acarbose dosing was: 50 mg before main meals initially with 50 mg increasing increments every 7 days until reaching a maximum dose of 300 mg/day.

Statistical Analysis

Statistical analysis was carried out in Microsoft Excel through ANOVA, with a 95% signficance rate.

 

Data Collection Summary:

Timing of Measurements

Fasting glucose and 2 hour post-prandial levels were obtained every consultation. In case one of the values was abnormal, new blood samples were collected 2 hr after lunch and dinner in order to establish the glucose profile and adjust dosage of selected therapy.

Newborns were evaluated for weight, macrosomia and large for gestational age (LGA) in the neonatal period after 48 hours.

Capillary glucose monitoring was perfomred in the 1st, 3rd and 6th hours after birth.

Dependent Variables

  • Glucose control in women with GDM
  • Fetal weight at birth
  • LGA at birth 
  • Newborn capillary glucose

Independent Variable

  • Insulin, glyburide or acarbose therapy in the treatment of GDM

Control Variables

 

Description of Actual Data Sample:

Initial N: 71 women, 1 excluded for severe asthma, resulting in 70 women.  Insulin = 27, glyburide = 24, acarbose = 19

Attrition (final N):  70 newborns

Age: Range from 21. 7 to 47.3

Ethnicity: Brazilian women

Other relevant demographics: within the public health section

Anthropometrics:No signficant differences between groups in age, number of gestations, BMI or weight gain.

Location: Public health hospital in Joinville SC, Brazil

 

Summary of Results:

 

Variables

Insulin (n=27)

Means and SD

Glyburide (n=24)

Means and SD

Acarbose (n=19)

Means and SD

Statistical signficance of groups (p value)

GA birth

38.5 (1.2) 38.1 (1.2) 38.2 (1.2) 0.42

Fetal weight

 

 3151.2 (407.2)

 3395.6 (524.4)

 3242.6 (400.6

0.15

LGA

 1 (3.7%)

 6 (25%)

 2 (10.5%)

 0.073
CG< 40 mg/dl 1 (3.7%) 8 (33.3%) 1 (5.3%) 0.006

CG 1 hr

57.8 (12.1) 50.9 (16.8) 57. 9 (16.1) 0.18
CG 3 hr 61.5 (9.5) 55.6 (13.0) 60.0 (14.7) 0.22
CG 6 hr 66.7 (9.4) 57.0 (10.6) 63.1 (11.9) 0.13

Neonatal characteristics of 70 newborns (means and standard deviation). Fetal weight at birth; LGA large for gestational age; CG - capillary glucose

Other Findings

Glucose level control was not achieved in 5 patients from the glyburide group (20.8%), and neither in 8 patients from the acarbose group (42.1%).

Author Conclusion:
We believe that glyburide and acarbose can be promising alternatives for the treatment of GDM. Glyburide  controlled glucose levels in most patients and it was  more efficient than acarbose. Glyburide showed a higher rate of macrosomia and neonatal hypoglycemia as compared to other therapies.
Funding Source:
Reviewer Comments:
Unclear what time period each consultation was. There was no mention of when blood glucose was monitored, what levels were found, or HgbA1c. There was also no mention of compliance to regimen.  Statistics not well described.  Groups not equally sized.
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? ???
  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? ???
3. Were study groups comparable? Yes
  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? Yes
  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? N/A
  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? No
  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? N/A
  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? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? ???
  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? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  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? ???
  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? ???
  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? ???
  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? No
  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? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  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)? ???
  8.6. Was clinical significance as well as statistical significance reported? ???
  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