Comparative Effectiveness of Metformin for Type 2 Diabetes With Chronic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 4,888
- 试验地点
- 2
- 主要终点
- Incidence of Severe Hypoglycemia Assessed from EMR
研究概览
简要总结
This is a proposal for a retrospective observational study of the safety of metformin use in patients with chronic kidney disease, compared to other commonly used diabetes drugs. It will be conducted using retrospective data from the New York City CDRN, Medicare administrate files, and New York State Medicaid administrative files, which will be linked and then deidentified prior to analysis.
详细描述
Specific aims are as follows:
Aim 1. For patients with Type 2 Diabetes Mellitus(T2DM) and Chronic Kidney Disease (CKD), compare metformin to alternative non-insulin diabetes drugs (sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors)) with respect to the key safety outcome of severe hypoglycemia. The primary hypothesis is that metformin will be superior to sulfonylurea in terms of severe hypoglycemia rates, and non-inferior to DPP-4 inhibitors. Secondary outcomes will include hospitalization for acidosis, hospitalization for hyperglycemia, acute myocardial infarction, stroke, heart failure hospitalization, and heart failure emergency room visit.
Aim 2. For patients with T2DM and CKD, compare metformin to alternative non-insulin diabetes drugs with respect to HbA1c reduction. The primary hypothesis is that metformin will be superior to DPP-4 inhibitors and non-inferior to sulfonylureas for HbA1c reduction (i.e., improvement in blood sugar). Secondary outcomes will include change in body-mass index (BMI) and kidney function, non-persistence to treatment, and progression to insulin use.
Aim 3. Examine the heterogeneity of treatment effects on hypoglycemia risk and HbA1c response across patient subgroups. The primary hypothesis is that metformin's advantages will be more pronounced in more severe CKD.
Aim 4 (data completeness): Using the linked Medicare-CDRN dataset, assess completeness of CDRN data for drugs and hospitalization among Medicare recipients. Specifically, we will use Medicare data from 2013-2016 as a gold standard and assess the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of INSIGHT CDRN data from those years in identifying hospitalizations and prevalent diabetes drug use among Medicare patients with T2DM (type 2 diabetes mellitus), and develop and validate an algorithm to identify patients for whom NPV and PPV for hospitalizations and all major diabetes drug classes exceed 80%. We hypothesize that such an algorithm will identify a population of a quarter of eligible Medicare patients in the CDRN who meet or exceed these standards for completeness of data.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A coded inpatient or outpatient T2DM diagnosis (ICD9/ICD10) and an antidiabetic medication prescription within the 90 days following the diagnosis date (CP1); a coded T2DM diagnosis and an outpatient glycolated hemoglobin (HbA1C) value≥6.5% within 90 days before or after the diagnosis date (CP2); or any antidiabetic medication prescription within 90 days before or after an outpatient HbA1C value ≥6.5% (CP3).
- •New use of a medication of interest (metformin, sulfonylurea, DPP4 inhibitor, SGLT2 inhibitor, or GLP1 receptor agonist
- •Estimated glomerular filtration rate (eGFR) of less than 60 ml/min within the month prior to the new medication
排除标准
- •Coded diagnoses of gestational diabetes
- •Coded diagnoses of prediabetes
- •Coded diagnoses of type 1 diabetes
- •Evidence of a positive beta human chorionic gonadotropin test as a marker for pregnancy during the 90 days before or after the index date
研究组 & 干预措施
GLP1 Receptor Agonist Cohort
Group of study participants having both Type 2 Diabetes and Chronic Kidney disease and meeting the study's inclusion criteria for whom a GLP1 receptor agonist was prescribed at baseline for this first time in each patient's medical history.
干预措施: GLP1 receptor agonist (Drug)
Metformin Cohort
Group of study participants having both Type 2 Diabetes and Chronic Kidney disease and meeting the study's inclusion criteria for whom metformin was prescribed at baseline for this first time in each patient's medical history.
干预措施: Metformin (Drug)
Sulfonylurea Cohort
Group of study participants having both Type 2 Diabetes and Chronic Kidney disease and meeting the study's inclusion criteria for whom sulfonylurea was prescribed at baseline for this first time in each patient's medical history.
干预措施: Sulfonylurea (Drug)
DPP4 Inhibitor Cohort
Group of study participants having both Type 2 Diabetes and Chronic Kidney disease and meeting the study's inclusion criteria for whom a DPP4 Inhibitor was prescribed at baseline for this first time in each patient's medical history.
干预措施: DPP-4 inhibitor (Drug)
SGLT2 Inhibitor Cohort
Group of study participants having both Type 2 Diabetes and Chronic Kidney disease and meeting the study's inclusion criteria for whom an SGLT2 Inhibitor was prescribed at baseline for this first time in each patient's medical history.
干预措施: SGLT2 inhibitor (Drug)
结局指标
主要结局
Incidence of Severe Hypoglycemia Assessed from EMR
时间窗: 18 Months
Comparing the time-to event outcomes between metformin and other index exposures. Severe Hypoglycemic events are defined as events resulting in emergency room, observation, or inpatient visits where hypoglycemia is the primary diagnosis
Difference in Glycosylated Hemoglobin (HbA1c) level (mmol/mol)
时间窗: 24 Months
Comparing the change in HbA1c in the metformin-initiator cohort to the changes reported in the sulfonylurea- and DPP4-I-initiator cohorts at 3-9 months following baseline. HbA1c will be measured in mmol/mol.
Heterogeneity of Treatment Effect Via Pre-specified Sub-Group Analyses
时间窗: 25 Months
Determine the extent of heterogeneity in treatment effect through the stratification of the sample population by covariate subgroups (age, sex, BMI, race; baseline history of CVD, liver disease, and heart failure; specific sulfonylurea or DPP-4 inhibitor, and levels of renal function and metformin dose as time-varying covariates) and through the use of machine learning techniques.
次要结局
- Incidence of acidosis, hospitalization for hyperglycemia, acute myocardial infarction, stroke, heart failure hospitalization, and heart failure emergency room visits(18 Months)
- Difference in Glycosylated Hemoglobin (HbA1c) level (mmol/mol)(24 Months)
- Difference in Body-Mass Index Assessed From EMR (BMI) (kg/m2)(24 Months)
- Difference in Laboratory-Measured eGFR (mL/min)(24 Months)