Cardiovascular Events and All-Cause Mortality with SGLT2 Inhibitors versus DPP-4 Inhibitors in Patients Starting Tyrosine Kinase Inhibitors: Protocol of a Target Trial Emulation

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Patients starting tyrosine kinase inhibitors (VEGFR-targeting, BCR-ABL, or BTK inhibitors). Intervention: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation vs. Dipeptidyl peptidase-4 inhibitor (DPP-4i) initiation. Primary outcome: Major adverse cardiovascular events.

Chia-Yu Hsu; Wei-Lun Chou; Jing-Huan Liao; Wei-Cheng Chang; Hsin-Yu Chen; Hong-Jie Jhou; Cho-Hao Lee; Po‐Huang Chen

doi:10.5281/zenodo.23768022

October 31, 2026Open Access

Cardiovascular Events and All-Cause Mortality with SGLT2 Inhibitors versus DPP-4 Inhibitors in Patients Starting Tyrosine Kinase Inhibitors: Protocol of a Target Trial Emulation

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Key result

SGLT2 inhibitors evaluated against DPP-4 inhibitors for MACE in patients starting tyrosine kinase inhibitors.

Why the study?

Does initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) compared to a dipeptidyl peptidase-4 inhibitor (DPP-4i) reduce major adverse cardiovascular events in adults starting tyrosine kinase inhibitors?

Key Points

To outline a target trial emulation protocol evaluating cardiovascular outcomes and all-cause mortality associated with initiating SGLT2 inhibitors versus DPP-4 inhibitors in patients receiving tyrosine kinase inhibitor therapy.
Target trial emulation protocol using electronic health records from the TriNetX Global Collaborative Network.
Population comprises adults initiating one of 15 tyrosine kinase inhibitors, including VEGFR-targeting, BCR-ABL, or BTK inhibitors, who concurrently start an SGLT2 inhibitor or a DPP-4 inhibitor.
Predefined specifications establish cohort criteria and coding definitions for the primary analysis along with 20 sensitivity analyses.
Because this publication describes a study protocol, empirical numerical findings, effect sizes, and per-arm event rates are not reported.
The designated primary outcome is major adverse cardiovascular events, and the key secondary outcome is all-cause mortality.

Study Design

Type

Cohort

Multicenter

Yes

Structured PICO

Does initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) compared to a dipeptidyl peptidase-4 inhibitor (DPP-4i) reduce major adverse cardiovascular events in adults starting tyrosine kinase inhibitors?

P

Population

Adults initiating one of 15 tyrosine kinase inhibitors (VEGFR-targeting, BCR-ABL, or BTK inhibitors) in the TriNetX Global Collaborative Network.

E

Exposure

Initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i)

C

Comparator

Initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i)

O

Outcome

Major adverse cardiovascular eventscomposite

This study protocol outlines a target trial emulation to evaluate whether SGLT2 inhibitors reduce major adverse cardiovascular events and all-cause mortality compared to DPP-4 inhibitors in patients initiating tyrosine kinase inhibitors.

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Implication

Emulation protocol compares SGLT2i vs DPP-4i on MACE in TKI users; leaves open CV effects in this population.

Abstract

This document is the protocol of a target trial emulation comparing initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) among adults starting one of 15 tyrosine kinase inhibitors (VEGFR-targeting, BCR-ABL, or BTK inhibitors) in the TriNetX Global Collaborative Network. The primary endpoint is major adverse cardiovascular events and the key secondary endpoint is all-cause mortality.

Discussion

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Cite This Study

Hsu et al. (2026) conducted a cohort in Patients starting tyrosine kinase inhibitors (VEGFR-targeting, BCR-ABL, or BTK inhibitors). Sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation vs. Dipeptidyl peptidase-4 inhibitor (DPP-4i) initiation was evaluated on Major adverse cardiovascular events. SGLT2 inhibitors versus DPP-4 inhibitors are being evaluated for major adverse cardiovascular events in adults starting tyrosine kinase inhibitors in this target trial emulation protocol.

synapsesocial.com/papers/6ae7d421edffb49629410490 https://doi.org/10.5281/zenodo.23768022

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Cardiovascular Events and All-Cause Mortality with SGLT2 Inhibitors versus DPP-4 Inhibitors in Patients Starting Tyrosine Kinase Inhibitors: Protocol of a Target Trial Emulation

Key Points

Study Design

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Cardiovascular Events and All-Cause Mortality with SGLT2 Inhibitors versus DPP-4 Inhibitors in Patients Starting Tyrosine Kinase Inhibitors: Protocol of a Target Trial Emulation

Key Points

Study Design

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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