Comparative Effectiveness of Metformin for Type 2 Diabetes With Chronic Kidney Disease

NCT03921242 | Completed FDA Drug

• 1 other identifier: 1809019555
• Study Type: observational
• Target: 4,888
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic

Outcome Measures

Primary Outcomes (3)

• Incidence of Severe Hypoglycemia Assessed from EMR

  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

  18 Months

• Difference in Glycosylated Hemoglobin (HbA1c) level (mmol/mol)

  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.

  24 Months

• Heterogeneity of Treatment Effect Via Pre-specified Sub-Group Analyses

  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.

  25 Months

Secondary Outcomes (4)

• 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

Study Arms (5)

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.

Drug: Metformin

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.

Drug: Sulfonylurea

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.

Drug: DPP-4 inhibitor

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.

Drug: SGLT2 inhibitor

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.

Drug: GLP1 receptor agonist

Interventions

Metformin DRUG

Newly Initiated and regular metformin dosage as prescribed by each patient's medical care provider

Metformin Cohort

Sulfonylurea DRUG

Newly initiated and regular sulfonylurea dosage as prescribed by each patient's medical care provider

Sulfonylurea Cohort

DPP-4 inhibitor DRUG

Newly initiated and regular DPP-4 inhibitor dosage as prescribed by each patient's medical care provider

DPP4 Inhibitor Cohort

SGLT2 inhibitor DRUG

Newly initiated and regular SGLT2 inhibitor dosage as prescribed by each patient's medical care provider

SGLT2 Inhibitor Cohort

GLP1 receptor agonist DRUG

Newly initiated and regular GLP1 receptor agonist dosage as prescribed by each patient's medical care provider

GLP1 Receptor Agonist Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

EHR data from two data sources (NYC and Mid-South CDRN's) will be linked to insurance claims data to identify adult patients (age \> 18) with T2DM and CKD, who are initiating metformin or one of the comparator drugs. Also, participants will further be required to have at least one prescription for metformin, sulfonylurea, or DPP-4 inhibitor; at least 6 months preceding that prescription in which none of those drugs are used; and an eGFR within 1 month prior to the index date (the date on which the drug of interest is started) of \< 60 mL/min

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (2)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic

Interventions

Metformin; Sulfonylurea Compounds; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Alvin Mushlin

  Weill Cornell Medical College/Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 19, 2019
• Study Start: August 1, 2019
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: November 9, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)