Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study

Type2 Diabetes Clinical Trial

— CER-4-T2D  

Official title:

Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05220917
• Other study ID #: 2021P001784
• Status: Active, not recruiting
• Start date: August 1, 2021
• Est. completion date: July 31, 2024

Study information

• Verified date: February 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To perform an observational analysis to emulate a target trial (i.e., a hypothetical pragmatic trial that would have answered the causal question of interest) comparing the effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas (SU), at the class and individual agent level, in head-to-head comparisons in patients with type 2 diabetes (T2D).

Description:

Aim 1: (1a.) To evaluate the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas (SU), at the class and individual agent level, in head-to-head comparisons with respect to cardiovascular (CV) events, mortality, renal events, and other patient-centered outcomes (e.g., time spent at home), in patients with T2D and moderate baseline CV risk (event rate ≤3%/year). (1b.) To examine heterogeneity in treatment effects by age, race/ethnicity, gender, levels of CV risk, including high (≥4%/year) and low risk (<2%/year), chronic kidney disease (CKD), frailty, and multimorbidity.

Aim 2: (2a.) To monitor and quantify the association of the initiation of SGLT2i, GLP-1RA, DPP-4i, or SU, at the class and individual agent level, with previously reported drug-related harms (e.g., diabetic ketoacidosis (DKA), fractures, amputations, pancreatitis, severe hypoglycemia). (2b.) To scan study data sources for signals of potential serious unanticipated drug-related adverse events, using a data-mining approach (tree-based scan statistics). (2c.) By using data generated in Aims 2a and 2b, to build treatment-specific outcome prediction models to identify individual patients' likelihood of drug-related harms, based on specific combinations of patient features.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 781430
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years for Optum Cliniformatics, IBM Marketscan, CPRD, and VHA, and = 65 years for Medicare FFS at cohort entry

• At least 12 months of continuous health plan enrollment (only claims) or registration with a general practitioner (CPRD) before and including cohort entry

• Diagnosis of T2D within 12 months before (or ever before in CPRD) and including cohort entry

• Low or moderate cardiovascular (CV) risk (=3% risk of CV events/year) at cohort entry *

• Metformin maintenance therapy, defined as 2 fills (or prescriptions in CPRD) of metformin monotherapy recorded within 6 months before and including cohort entry

Exclusion Criteria:

• Missing age or gender information

• Nursing care admission within 12 months before and including cohort entry (criteria ignored in CPRD)

• Diagnosis of type 1 diabetes within 12 months before and including cohort entry

• Diagnosis of secondary or gestational diabetes within 12 months before and including cohort entry

• Any insulin fill or prescription within 12 months before and including cohort entry

• Diagnosis of end stage renal disease (stage = 5) within 12 months before and including cohort entry

• Diagnosis of acute or chronic pancreatitis within 12 months before and including cohort entry

• Diagnosis of cirrhosis or acute hepatitis within 12 months before and including cohort entry

• Diagnosis of MEN-2 within 12 months before and including cohort entry

• Recorded solid organ transplant code within 12 months before and including cohort entry

• Patients with recorded initiation of more than one agent within a comparator class at cohort entry

Related Conditions & MeSH terms

• Cardiovascular Events
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Renal Disease
• Type2 Diabetes

Intervention

Drug:
• SGLT2 inhibitor
Any SGLT2i dispensing claim
• DPP-4 inhibitor
Any DPP-4 inhibitor claim
• GLP-1RA
Any SGLT2i dispensing claim
• 2nd generation SU
Any 2nd generation SU claim

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	McGill University, Patient-Centered Outcomes Research Institute, VA Boston Healthcare System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CKD progression	Sustained decrease in eGFR, KRT (maintenance dialysis and kidney transplantation), kidney death; * exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Sustained decrease in eGFR	* exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Kidney replacement therapy (KRT)	* exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Kidney death	* exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Kidney failure	(sustained eGFR <15 ml/min/1.73m2, maintenance dialysis and kidney transplant); * exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Early kidney disease	Defined by change in eGFR in patients with baseline eGFR > 60; * exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Glycemic control	Defined by HbA1c change in patients with available baseline HbA1c	through study completion, an average of 1 year
Other	Insulin initiation		through study completion, an average of 1 year
Other	Weight loss or gain	Defined by weight change in patients with available baseline weight; * exploratory outcome, since no validated claim-based outcome definition is currently available	through study completion, an average of 1 year
Other	Diabetic ketoacidosis	exposure of interest - SGLT-2i	through study completion, an average of 1 year
Other	Bone fractures	exposure of interest - SGLT-2i	through study completion, an average of 1 year
Other	Lower-limb amputations	exposure of interest - SGLT-2i	through study completion, an average of 1 year
Other	Acute kidney injury	exposure of interest - all drug classes	through study completion, an average of 1 year
Other	Urinary infections	exposure of interest - SGLT-2i	through study completion, an average of 1 year
Other	Genital infections	exposure of interest - SGLT-2i	through study completion, an average of 1 year
Other	Acute pancreatitis	exposure of interest - GLP1 RA, DPP4i	through study completion, an average of 1 year
Other	Biliary events	exposure of interest - GLP1 RA, DPP4i	through study completion, an average of 1 year
Other	Severe hypoglycemia	exposure of interest - SU	through study completion, an average of 1 year
Other	Short-term retinopathy progression	exposure of interest - GLP1 RA; * exploratory outcomes, since no validated outcome definition is currently available	through study completion, an average of 1 year
Other	Home time	Time spent out of hospital and skilled nursing facility, Time to Nursing Home Placement	through study completion, an average of 1 year
Other	Medication persistence	Time to discontinuation	through study completion, an average of 1 year
Other	Switching patterns	Treatment trajectories: patterns of use following initiation of treatment under study. To be illustrated using concentric circle diagrams or Sankey diagrams as appropriate.	through study completion, an average of 1 year
Primary	MACE	Myocardial Infarction, Ischemic Stroke, Cardiovascular mortality	through study completion, an average of 1 year
Primary	Modified MACE	Myocardial Infarction, Ischemic Stroke, All-Cause mortality	through study completion, an average of 1 year
Primary	Hospitalization for Heart Failure (HHF) Hospitalization for Heart Failure (HHF)		through study completion, an average of 1 year
Secondary	Myocardial Infarction (MI)		through study completion, an average of 1 year
Secondary	Stroke		through study completion, an average of 1 year
Secondary	Cardiovascular Mortality		through study completion, an average of 1 year
Secondary	All-cause mortality		through study completion, an average of 1 year
Secondary	Coronary revascularization		through study completion, an average of 1 year