Xulei Liu

Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study

BACKGROUNDnThe effects of sulfonylureas and metformin on outcomes of cardiovascular disease (CVD) in type 2 diabetes are not well-characterized.nnnOBJECTIVEnTo compare the effects of sulfonylureas and metformin on CVD outcomes (acute myocardial infarction and stroke) or death.nnnDESIGNnRetrospective cohort study.nnnSETTINGnNational Veterans Health Administration databases linked to Medicare files.nnnPATIENTSnVeterans who initiated metformin or sulfonylurea therapy for diabetes. Patients with chronic kidney disease or serious medical illness were excluded.nnnMEASUREMENTSnComposite outcome of hospitalization for acute myocardial infarction or stroke, or death, adjusted for baseline demographic characteristics; medications; cholesterol, hemoglobin A1c, and serum creatinine levels; blood pressure; body mass index; health care utilization; and comorbid conditions.nnnRESULTSnAmong 253 690 patients initiating treatment (98 665 with sulfonylurea therapy and 155 025 with metformin therapy), crude rates of the composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4 per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years; adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI, 1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and albuminuria; in a propensity score-matched cohort analysis; and in sensitivity analyses.nnnLIMITATIONnMost of the veterans in the study population were white men; data on women and minority groups were limited but reflective of the Veterans Health Administration population.nnnCONCLUSIONnUse of sulfonylureas compared with metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death.nnnPRIMARY FUNDING SOURCEnAgency for Healthcare Research and Quality and the U.S. Department of Health and Human Services.

Association Between Intensification of Metformin Treatment With Insulin vs Sulfonylureas and Cardiovascular Events and All-Cause Mortality Among Patients With Diabetes

IMPORTANCEnPreferred second-line medication for diabetes treatment after metformin failure remains uncertain.nnnOBJECTIVEnTo compare time to acute myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea.nnnDESIGN, SETTING, AND PARTICIPANTSnRetrospective cohort constructed with national Veterans Health Administration, Medicare, and National Death Index databases. The study population comprised veterans initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. Propensity score matching on characteristics was performed, matching each participant who added insulin to 5 who added a sulfonylurea. Patients were followed through September 2011 for primary analyses or September 2009 for cause-of-death analyses.nnnMAIN OUTCOMES AND MEASURESnRisk of a composite outcome of AMI, stroke hospitalization, or all-cause death was compared between therapies with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, cholesterol level, hemoglobin A1c level, creatinine level, blood pressure, body mass index, and comorbidities.nnnRESULTSnAmong 178,341 metformin monotherapy patients, 2948 added insulin and 39,990 added a sulfonylurea. Propensity score matching yielded 2436 metformin + insulin and 12,180 metformin + sulfonylurea patients. At intensification, patients had received metformin for a median of 14 months (IQR, 5-30), and hemoglobin A1c level was 8.1% (IQR, 7.2%-9.9%). Median follow-up after intensification was 14 months (IQR, 6-29 months). There were 172 vs 634 events for the primary outcome among patients who added insulin vs sulfonylureas, respectively (42.7 vs 32.8 events per 1000 person-years; adjusted hazard ratio [aHR], 1.30; 95% CI, 1.07-1.58; P =u2009.009). Acute myocardial infarction and stroke rates were statistically similar, 41 vs 229 events (10.2 and 11.9 events per 1000 person-years; aHR, 0.88; 95% CI, 0.59-1.30; P =u2009.52), whereas all-cause death rates were 137 vs 444 events, respectively (33.7 and 22.7 events per 1000 person-years; aHR, 1.44; 95% CI, 1.15-1.79; P =u2009.001). There were 54 vs 258 secondary outcomes: AMI, stroke hospitalizations, or cardiovascular deaths (22.8 vs 22.5 events per 1000 person-years; aHR, 0.98; 95% CI, 0.71-1.34; P =u2009.87).nnnCONCLUSIONS AND RELEVANCEnAmong patients with diabetes who were receiving metformin, the addition of insulin vs a sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality. These findings require further investigation to understand risks associated with insulin use in these patients.

Comparative effectiveness of incident oral antidiabetic drugs on kidney function.

Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who filled an incident oral antidiabetic drug prescription for metformin, sulfonylurea, or rosiglitazone, and had an estimated glomerular filtration rate (eGFR) of 60u2009ml/min or better. The primary composite outcome was a persistent decline in eGFR from baseline of 25% or more (eGFR event) or a diagnosis of end-stage renal disease (ESRD). The secondary outcome was an eGFR event, ESRD, or death. Sensitivity analyses included using a more stringent definition of the eGFR event requiring an eGFR <60u2009ml/min per 1.73u2009m2 in addition to the 25% or more decline; controlling for baseline proteinuria thereby restricting data to 15,065 patients; and not requiring persistent treatment with the initial oral antidiabetic drug. Compared to patients using metformin, sulfonylurea users had an increased risk for both the primary and the secondary outcome, each with an adjusted hazard ratio of 1.20. Results of sensitivity analyses were consistent with the main findings. The risk associated with rosiglitazone was similar to metformin for both outcomes. Thus, compared to metformin, oral antidiabetic drug treatment with sulfonylureas increased the risk of a decline in eGFR, ESRD, or death.

Clinical Inertia: A Common Barrier to Changing Provider Prescribing Behavior

BACKGROUNDnA cross-sectional content analysis nested within a randomized, controlled trial was conducted to collect information on provider responses to computer alerts regarding guideline recommendations for patients with suboptimal hypertension care.nnnMETHODSnParticipants were providers who cared for 1,017 patients with uncontrolled hypertension on a single antihypertensive agent within Veterans Affairs primary care clinics. All reasons for action or inaction were sorted into a framework to explain the variation in guideline adaptation.nnnRESULTSnThe 184 negative provider responses to computer alerts contained explanations for not changing patient treatment; 76 responses to the alerts were positive, that is, the provider was going to make a change in antihypertensive regimen. The negative responses were categorized as: inertia of practice (66%), lack of agreement with specific guidelines (5%), patient-based factors (17%), environmental factors (10%), and lack of knowledge (2%). Most of the 135 providers classified as inertia of practice indicated, Continue current medications and I will discuss at the next visit. The median number of days until the next visit was 45 days (interquartile range, 29 to 78 days).nnnDISCUSSIONnClinical inertia was the primary reason for failing to engage in otherwise indicated treatment change in a subgroup of patients. A framework was provided as a taxonomy for classification of provider barriers.

Measuring and Comparing Safety Climate in Intensive Care Units

Background:Learning about the factors that influence safety climate and improving the methods for assessing relative performance among hospital or units would improve decision-making for clinical improvement. Objectives:To measure safety climate in intensive care units (ICU) owned by a large for-profit integrated health delivery systems; identify specific provider, ICU, and hospital factors that influence safety climate; and improve the reporting of safety climate data for comparison and benchmarking. Research Design:We administered the Safety Attitudes Questionnaire (SAQ) to clinicians, staff, and administrators in 110 ICUs from 61 hospitals. Subjects:A total of 1502 surveys (43% response) from physicians, nurses, respiratory therapists, pharmacists, mangers, and other ancillary providers. Measures:The survey measured safety climate across 6 domains: teamwork climate; safety climate; perceptions of management; job satisfaction; working conditions; and stress recognition. Percentage of positive scores, mean scores, unadjusted random effects, and covariate-adjusted random effect were used to rank ICU performance. Results:The cohort was characterized by a positive safety climate. Respondents scored perceptions of management and working conditions significantly lower than the other domains of safety climate. Respondent job type was significantly associated with safety climate and domain scores. There was modest agreement between ranking methodologies using raw scores and random effects. Conclusions:The relative proportion of job type must be considered before comparing safety climate results across organizational units. Ranking methodologies based on raw scores and random effects are viable for feedback reports. The use of covariate-adjusted random effects is recommended for hospital decision-making.

Comparisons of Persistence and Durability Among Three Oral Antidiabetic Therapies Using Electronic Prescription‐Fill Data: The Impact of Adherence Requirements and Stockpiling

Two important challenges are inherent in the design of studies using prescription data from electronic health records: how to define the minimum level of adherence that would qualify as “continuous drug use” and how to handle stockpiling of medications. Generally, the sensitivity of a studys conclusions to these design choices is not analyzed. In our study, covariate adjusted Cox models were used to compare persistence and durability with respect to three common oral antidiabetic therapies in a cohort of 12,697 incident users. Assuming 50% stockpiling, sulfonylurea therapy, as compared with metformin, showed a significantly lower risk of nonpersistence (changing or stopping therapy) when no gap days were allowed (HR 0.95, P = 0.032), no significant difference when 14 gap days were allowed (HR 0.99, P = 0.536), and significantly greater risk of nonpersistence when 30 gap days were allowed (HR 1.05, P = 0.046). All the drug comparisons showed statistically significant effects in both directions, the risk of nonpersistence increasing or decreasing depending on the design parameters.

Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.

We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control.

Reweighted Mahalanobis distance matching for cluster-randomized trials with missing data.

This paper introduces an improved tool for designing matched‐pairs randomized trials. The tool allows the incorporation of clinical and other knowledge regarding the relative importance of variables used in matching and allows for multiple types of missing data. The method is illustrated in the context of a cluster‐randomized trial. A Web application and an R package are introduced to implement the method and incorporate recent advances in the area.

Initiation of sulfonylureas versus metformin is associated with higher blood pressure at one year.

To determine if incident oral antidiabetic drug (OAD) use was associated with 12‐month systolic blood pressure (BP) and if this was mediated through body mass index (BMI) changes.

The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: A retrospective cohort

Effects of oral antidiabetic drugs (OADs) on lipids may influence cardiovascular outcomes. Our aim was to compare time to initiation of lipid lowering medication (LLM) and 12‐month lipid profiles among new OAD users.