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

NCT05220917 | Active Not Recruiting FDA Drug

• 1 other identifier: 2021P001784
• Study Type: observational
• Target: 781,430
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Cardiovascular Events; Type2 Diabetes; Renal Disease

Outcome Measures

Primary Outcomes (3)

• MACE

  Myocardial Infarction, Ischemic Stroke, Cardiovascular mortality

  through study completion, an average of 1 year

• Modified MACE

  Myocardial Infarction, Ischemic Stroke, All-Cause mortality

  through study completion, an average of 1 year

• Hospitalization for Heart Failure (HHF) Hospitalization for Heart Failure (HHF)

  through study completion, an average of 1 year

Secondary Outcomes (5)

• Myocardial Infarction (MI)

  through study completion, an average of 1 year

• Stroke

  through study completion, an average of 1 year

• Cardiovascular Mortality

  through study completion, an average of 1 year

• All-cause mortality

  through study completion, an average of 1 year

• Coronary revascularization

  through study completion, an average of 1 year

Other Outcomes (22)

• CKD progression

  through study completion, an average of 1 year

• Sustained decrease in eGFR

  through study completion, an average of 1 year

• Kidney replacement therapy (KRT)

  through study completion, an average of 1 year

Study Arms (19)

SGLT-2i (Comparison 1)

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

Drug: SGLT2 inhibitor

DPP-4i (Comparison 1)

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

Drug: DPP-4 inhibitor

SGLT-2i (Comparison 2)

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

Drug: SGLT2 inhibitor

GLP-1 RA (Comparison 2)

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

Drug: GLP-1RA

GLP-1 RA (Comparison 3)

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

Drug: GLP-1RA

DPP-4i (Comparison 3)

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

Drug: DPP-4 inhibitor

SGLT-2i (Comparison 4)

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

Drug: SGLT2 inhibitor

SU (Comparison 4)

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

Drug: 2nd generation SU

GLP-1 RA (Comparison 5)

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

Drug: GLP-1RA

SU (Comparison 5)

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

Drug: 2nd generation SU

DPP-4i (Comparison 6)

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

Drug: DPP-4 inhibitor

SU (Comparison 6)

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

Drug: 2nd generation SU

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

Drug: SGLT2 inhibitor

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

Drug: GLP-1RA

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

Drug: DPP-4 inhibitor

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

Drug: 2nd generation SU

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

Drug: SGLT2 inhibitor

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

Drug: GLP-1RA

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

Drug: DPP-4 inhibitor

Interventions

SGLT2 inhibitor DRUG

Any SGLT2i dispensing claim

Also known as: 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

SGLT-2i (Comparison 1); SGLT-2i (Comparison 2); SGLT-2i (Comparison 4); SGLT2i (Comparison 7); SGLT2i (Comparison 8)

DPP-4 inhibitor DRUG

Any DPP-4 inhibitor claim

Also known as: 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

DPP-4i (Comparison 1); DPP-4i (Comparison 3); DPP-4i (Comparison 6); DPP-4i (Comparison 7); DPP-4i (Comparison 8)

GLP-1RA DRUG

Any SGLT2i dispensing claim

Also known as: INSULIN DEGLUDEC/LIRAGLUTIDE*, INSULIN GLARGINE, HUMAN RECOMBINANT ANALOG/LIXISENATIDE*, LIXISENATIDE, LIRAGLUTIDE, DULAGLUTIDE, SEMAGLUTIDE, ALBIGLUTIDE, EXENATIDE MICROSPHERES, EXENATIDE

GLP-1 RA (Comparison 2); GLP-1 RA (Comparison 3); GLP-1 RA (Comparison 5); GLP-1 RA (Comparison 7); GLP-1 RA (Comparison 8)

2nd generation SU DRUG

Any 2nd generation SU claim

Also known as: PIOGLITAZONE HCL/GLIMEPIRIDE, ROSIGLITAZONE MALEATE/GLIMEPIRIDE, GLIPIZIDE/METFORMIN HCL, GLYBURIDE,MICRONIZED, GLYBURIDE/METFORMIN HCL, GLIMEPIRIDE, GLYBURIDE, GLIPIZIDE

SU (Comparison 4); SU (Comparison 5); SU (Comparison 6); SU (Comparison 7)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Optum and MarketScan databases are U.S. research claims databases that include adults with employer-based health plans, with nationwide coverage for over 60 million Americans, and meaningful numbers of patients ≥65 years from Medicare Advantage plans, employer-sponsored plans covering seniors, and Medicare supplemental insurance plans. Medicare FFS is a U.S. federal health insurance program providing coverage to individuals ≥65 years and to younger individuals with disabilities. The Partners RPDR captures longitudinal EHR data for all patients that receive care at 2 large health care provider networks in the Boston metro area. The VHA is the largest integrated national health system, serving over 12 million U.S. Veterans. The VHA database includes demographic, diagnostic and procedure information from inpatient/outpatient encounters. The CPRD is comprised of two large, computerized databases of longitudinal primary care records, GOLD and Aurum, for \>50 million UK patients.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Patient-Centered Outcomes Research Institute: collaborator
• VA Boston Healthcare System: collaborator
• McGill University: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin; Metformin; dapagliflozin; empagliflozin; Linagliptin; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Pioglitazone; Simvastatin; IDegLira; Insulin Glargine; lixisenatide; Liraglutide; dulaglutide; semaglutide; rGLP-1 protein; Exenatide; Rosiglitazone; glimepiride; Glipizide; Glyburide

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Biguanides; Guanidines; Amidines; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines; Triazoles; Azoles; Pyrazines; Protease Inhibitors; Enzyme Inhibitors; Thiazolidinediones; Thiazoles; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Sulfonylurea Compounds; Sulfones; Urea; Amides

Study Officials

• Elisabetta Patorno, MD, DrPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: February 2, 2022
• Study Start: August 1, 2021
• Primary Completion: January 31, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

US (1)