Pharmacological Treatment of Gestational Diabetes and Association with Adverse Maternal and Neonatal Outcomes

Background: In the United States, insulin is the only approved treatment for gestational diabetes (GDM). Glyburide has been used off-label as an alternative but there is still uncertainty regarding its safety and effectiveness in pregnancy. Purpose: 1) To identify trends and factors associated with use of glyburide, 2) to estimate the association between glyburide and adverse maternal or neonatal outcomes. Methods: We conducted a retrospective cohort study of commercially insured women with GDM with a pharmacy claim for glyburide or insulin 150 days prior to delivery, identified in an administrative claims database from 2000-2011. We excluded women 50 years, with prior type 2 diabetes, or multiple gestations. We estimated trends over time in the use of glyburide versus insulin. Binomial regression was used to estimate prevalence ratios (PR) and 95% CI for the association between covariates of interest and treatment with glyburide. We used inverse probability of treatment weights to adjust for confounding and binomial regression to estimate risk ratios (RR), risk differences (RD) and their 95% confidence intervals (CI). Results: Among 9,180 women who met inclusion criteria, 54% were treated with glyburide. From 2000-2011, glyburide use increased steeply from 8.5% to 64.5%. Women with metabolic syndrome (0.71 CI 0.50, 0.99) and hypothyroidism (0.89 CI 0.81, 0.97) were less likely to be treated with glyburide. After weighting, newborns from women treated with glyburide were at increased risk for NICU admission (1.39 CI 1.21, 1.59), respiratory distress (1.60 CI 1.21, 2.11), hypoglycemia (1.39 CI 1.00, 1.94), birth injury (1.36 CI 1.01, 1.84) and large for gestational age (1.43 CI 1.16, 1.76) compared to those treated with insulin. The absolute increase in risk in the glyburide group was 2.9% (CI 1.69, 4.00) for NICU admission, 1.4% (CI 0.60, 2.20) for large for gestational age and 1.1% (CI 0.46, 1.68) for respiratory distress. Conclusions: Glyburide has replaced insulin as the preferred treatment for GDM over the last decade. Newborns from mothers treated with glyburide are more likely to experience adverse events. Identification of subgroups of women more likely to benefit from glyburide is a public health priority.Doctor of Philosoph

Association of Adverse Pregnancy Outcomes With Glyburide vs Insulin in Women With Gestational Diabetes

IMPORTANCE: Glyburide is thought to be safe for use during pregnancy for treatment of gestational diabetes mellitus (GDM). However, there are limited data on the effectiveness of glyburide when compared with insulin as used in a real-world setting. OBJECTIVE: To estimate the risk of adverse maternal and neonatal outcomes in women with GDM treated with glyburide compared with insulin. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of a population-based cohort from a nationwide US employer-based insurance claims database from January 1, 2000, to December 31, 2011. We identified women with GDM and their newborns. We excluded those with type 1 or 2 diabetes and those younger than 15 years or older than 45 years. EXPOSURES: Treatment with glyburide or insulin during pregnancy within 150 days before delivery. MAIN OUTCOMES AND MEASURES: We used binomial regression to estimate risk ratios (RRs) and risk differences with 95% confidence intervals for the association of glyburide with diagnosis codes for obstetric trauma, cesarean delivery, birth injury, preterm birth, hypoglycemia, respiratory distress, jaundice, large for gestational age, and hospitalization in the neonatal intensive care unit. Inverse probability of treatment weights were used to adjust for maternal characteristics that differed between the treatment groups. RESULTS: Among 110,879 women with GDM, 9173 women (8.3%) were treated with glyburide (n = 4982) or insulin (n = 4191). After adjusting for differences at baseline, newborns of women treated with glyburide were at increased risk for neonatal intensive care unit admission (RR = 1.41; 95% CI, 1.23-1.62), respiratory distress (RR = 1.63; 95% CI, 1.23-2.15), hypoglycemia (RR = 1.40; 95% CI, 1.00-1.95), birth injury (RR = 1.35; 95% CI, 1.00-1.82), and large for gestational age (RR = 1.43; 95% CI, 1.16-1.76) compared with those treated with insulin; they were not at increased risk for obstetric trauma (RR = 0.92; 95% CI, 0.71-1.20), preterm birth (RR = 1.06; 95% CI, 0.93-1.21), or jaundice (RR = 0.96; 95% CI, 0.48-1.91). The risk of cesarean delivery was 3% lower in the glyburide group (adjusted RR = 0.97; 95% CI, 0.93-1.00). The risk difference associated with glyburide was 2.97% (95% CI, 1.82-4.12) for neonatal intensive care unit admission, 1.41% (95% CI, 0.61-2.20) for large for gestational age, and 1.11% (95% CI, 0.50-1.72) for respiratory distress. CONCLUSIONS AND RELEVANCE: Newborns from privately insured mothers treated with glyburide were more likely to experience adverse outcomes than those from mothers treated with insulin. Given the widespread use of glyburide, further investigation of these differences in pregnancy outcomes is a public health priority

Trends in Glyburide Compared With Insulin Use for Gestational Diabetes Treatment in the United States, 2000–2011

To describe trends and identify factors associated with choice of pharmacotherapy for gestational diabetes (GDM) from 2000–2011 using a healthcare claims database

Impact of different interventions on preventing suicide and suicide attempt among children and adolescents in the United States: a microsimulation model study

IntroductionDespite considerable investment in suicide prevention since 2001, there is limited evidence for the effect of suicide prevention interventions among children and adolescents. This study aimed to estimate the potential population impact of different interventions in preventing suicide-related behaviors in children and adolescents.MethodsA microsimulation model study used data from national surveys and clinical trials to emulate the dynamic processes of developing depression and care-seeking behaviors among a US sample of children and adolescents. The simulation model examined the effect of four hypothetical suicide prevention interventions on preventing suicide and suicide attempt in children and adolescents as follows: (1) reduce untreated depression by 20, 50, and 80% through depression screening; (2) increase the proportion of acute-phase treatment completion to 90% (i.e., reduce treatment attrition); (3) suicide screening and treatment among the depressed individuals; and (4) suicide screening and treatment to 20, 50, and 80% of individuals in medical care settings. The model without any intervention simulated was the baseline. We estimated the difference in the suicide rate and risk of suicide attempts in children and adolescents between baseline and different interventions.ResultsNo significant reduction in the suicide rate was observed for any of the interventions. A significant decrease in the risk of suicide attempt was observed for reducing untreated depression by 80%, and for suicide screening to individuals in medical settings as follows: 20% screened: −0.68% (95% credible interval (CI): −1.05%, −0.56%), 50% screened: −1.47% (95% CI: −2.00%, −1.34%), and 80% screened: −2.14% (95% CI: −2.48%, −2.08%). Combined with 90% completion of acute-phase treatment, the risk of suicide attempt changed by −0.33% (95% CI: −0.92%, 0.04%), −0.56% (95% CI: −1.06%, −0.17%), and −0.78% (95% CI: −1.29%, −0.40%) for reducing untreated depression by 20, 50, and 80%, respectively. Combined with suicide screening and treatment among the depressed, the risk of suicide attempt changed by −0.27% (95% CI: −0.dd%, −0.16%), −0.66% (95% CI: −0.90%, −0.46%), and −0.90% (95% CI: −1.10%, −0.69%) for reducing untreated depression by 20, 50, and 80%, respectively.ConclusionReducing undertreatment (the untreated and dropout) of depression and suicide screening and treatment in medical care settings may be effective in preventing suicide-related behaviors in children and adolescents

Use of Combination Antihypertensive Therapy Initiation in Older Americans without Prevalent Cardiovascular Disease

To describe new users of antihypertensives and identify predictors of combination therapy initiation among older Americans