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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

781430 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-08-01

Study Completion Date

2026-07-01

Brief Summary

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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).

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Detailed Description

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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.

Conditions

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Cardiovascular Events Type2 Diabetes Renal Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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SGLT-2i (Comparison 1)

For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP4i - referent group

SGLT2 inhibitor

Intervention Type DRUG

Any SGLT2i dispensing claim

DPP-4i (Comparison 1)

For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP-4i - referent group

DPP-4 inhibitor

Intervention Type DRUG

Any DPP-4 inhibitor claim

SGLT-2i (Comparison 2)

For SGLT-2i vs GLP-1 RA SGLT-2i - exposure group GLP-1 RA - referent group

SGLT2 inhibitor

Intervention Type DRUG

Any SGLT2i dispensing claim

GLP-1 RA (Comparison 2)

For SGLT-2i vs GLP-1 RA SGLT-2i - exposure group GLP-1 RA - referent group

GLP-1RA

Intervention Type DRUG

Any SGLT2i dispensing claim

GLP-1 RA (Comparison 3)

For GLP-1 RA vs DPP-4i GLP-1 RA - exposure group DPP-4i - referent group

GLP-1RA

Intervention Type DRUG

Any SGLT2i dispensing claim

DPP-4i (Comparison 3)

For GLP-1 RA vs DPP-4i GLP-1 RA - exposure group DPP-4i - referent group

DPP-4 inhibitor

Intervention Type DRUG

Any DPP-4 inhibitor claim

SGLT-2i (Comparison 4)

For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group

SGLT2 inhibitor

Intervention Type DRUG

Any SGLT2i dispensing claim

SU (Comparison 4)

For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group

2nd generation SU

Intervention Type DRUG

Any 2nd generation SU claim

GLP-1 RA (Comparison 5)

For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group

GLP-1RA

Intervention Type DRUG

Any SGLT2i dispensing claim

SU (Comparison 5)

For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group

2nd generation SU

Intervention Type DRUG

Any 2nd generation SU claim

DPP-4i (Comparison 6)

For DPP-4i vs SU DPP-4i - exposure group SU - referent group

DPP-4 inhibitor

Intervention Type DRUG

Any DPP-4 inhibitor claim

SU (Comparison 6)

For DPP-4i vs SU DPP-4i - exposure group SU - referent group

2nd generation SU

Intervention Type DRUG

Any 2nd generation SU claim

SGLT2i (Comparison 7)

For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group

SGLT2 inhibitor

Intervention Type DRUG

Any SGLT2i dispensing claim

GLP-1 RA (Comparison 7)

For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group

GLP-1RA

Intervention Type DRUG

Any SGLT2i dispensing claim

DPP-4i (Comparison 7)

For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group

DPP-4 inhibitor

Intervention Type DRUG

Any DPP-4 inhibitor claim

SU (Comparison 7)

For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group

2nd generation SU

Intervention Type DRUG

Any 2nd generation SU claim

SGLT2i (Comparison 8)

For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group

SGLT2 inhibitor

Intervention Type DRUG

Any SGLT2i dispensing claim

GLP-1 RA (Comparison 8)

For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group

GLP-1RA

Intervention Type DRUG

Any SGLT2i dispensing claim

DPP-4i (Comparison 8)

For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group

DPP-4 inhibitor

Intervention Type DRUG

Any DPP-4 inhibitor claim

Interventions

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SGLT2 inhibitor

Any SGLT2i dispensing claim

Intervention Type DRUG

DPP-4 inhibitor

Any DPP-4 inhibitor claim

Intervention Type DRUG

GLP-1RA

Any SGLT2i dispensing claim

Intervention Type DRUG

2nd generation SU

Any 2nd generation SU claim

Intervention Type DRUG

Other Intervention Names

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CANAGLIFLOZIN CANAGLIFLOZIN/METFORMIN HCL DAPAGLIFLOZIN PROPANEDIOL/METFORMIN HCL DAPAGLIFLOZIN PROPANEDIOL EMPAGLIFLOZIN EMPAGLIFLOZIN/METFORMIN HCL ERTUGLIFLOZIN PIDOLATE/METFORMIN HCL ERTUGLIFLOZIN PIDOLATE EMPAGLIFLOZIN/LINAGLIPTIN EMPAGLIFLOZIN/LINAGLIPTIN/METFORMIN HCL DAPAGLIFLOZIN PROPANEDIOL/SAXAGLIPTIN HCL ERTUGLIFLOZIN PIDOLATE/SITAGLIPTIN PHOSPHATE ALOGLIPTIN BENZOATE/METFORMIN HCL ALOGLIPTIN BENZOATE ALOGLIPTIN BENZOATE/PIOGLITAZONE HCL SAXAGLIPTIN HCL SAXAGLIPTIN HCL/METFORMIN HCL LINAGLIPTIN LINAGLIPTIN/METFORMIN HCL SITAGLIPTIN PHOSPHATE/METFORMIN HCL SITAGLIPTIN PHOSPHATE SITAGLIPTIN PHOSPHATE/SIMVASTATIN DAPAGLIFLOZIN PROPANEDIOL/SAXAGLIPTIN HCL EMPAGLIFLOZIN/LINAGLIPTIN EMPAGLIFLOZIN/LINAGLIPTIN/METFORMIN HCL ERTUGLIFLOZIN PIDOLATE/SITAGLIPTIN PHOSPHATE INSULIN DEGLUDEC/LIRAGLUTIDE* INSULIN GLARGINE, HUMAN RECOMBINANT ANALOG/LIXISENATIDE* LIXISENATIDE LIRAGLUTIDE DULAGLUTIDE SEMAGLUTIDE ALBIGLUTIDE EXENATIDE MICROSPHERES EXENATIDE PIOGLITAZONE HCL/GLIMEPIRIDE ROSIGLITAZONE MALEATE/GLIMEPIRIDE GLIPIZIDE/METFORMIN HCL GLYBURIDE,MICRONIZED GLYBURIDE/METFORMIN HCL GLIMEPIRIDE GLYBURIDE GLIPIZIDE

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No