Lung Cancer Risk in Type 2 Diabetes With COPD: SGLT2 Inhibitors vs. Sulfonylureas

Lung Cancer Incidence in Patients With Type 2 Diabetes and COPD: A Real-World Retrospective Cohort Study Comparing SGLT2 Inhibitors and Sulfonylureas

The goal of this observational study is to learn if a specific diabetes medicine can lower the risk of lung cancer in people with type 2 diabetes and chronic obstructive pulmonary disease (COPD).

The main question it aims to answer is:

- Does taking medicines called SGLT2 inhibitors lower the chance of getting lung cancer compared to medicines called sulfonylureas?

Researchers will compare the medical records of people taking SGLT2 inhibitors to those taking sulfonylureas to see if the SGLT2 group has fewer cases of lung cancer.

Participants will not need to visit a doctor or take new medicines for this study. Researchers will use information from existing medical records to answer the research question.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Lung Cancer (Diagnosis); COPD (Chronic Obstructive Pulmonary Disease)
• Intervention / Treatment: Drug: SGLT2 inhibitor; Drug: Sulfonylureas (SU); Drug: DPP4 inhibitors

Detailed Description

Study Design: This is a comparative effectiveness research study utilizing large-scale, population-based Real-World Data (RWD). By analyzing longitudinal data from existing medical records, researchers will emulate a target trial to minimize bias and provide robust estimates of the treatment effect.

Statistical Analysis Plan: The study employs a rigorous analytic framework consisting of a primary analysis and multiple sensitivity analyses to ensure the validity of the findings:

Primary Analysis: A comparison of SGLT2 inhibitors versus sulfonylureas using an Intention-To-Treat (ITT) framework, with follow-up censored upon treatment switching to estimate the effect of the initial treatment choice.

Sensitivity Analysis 1 (Active Comparator): A comparison of DPP-4 inhibitors versus SGLT2 inhibitors using the same ITT framework (censoring on switching) to assess the consistency of the results against an alternative second-line antidiabetic class.

Sensitivity Analysis 2 (As-Treated): A comparison of SGLT2 inhibitors versus sulfonylureas using an As-Treated approach, defining continuous use with a permissible gap (grace period) of 60 days between prescriptions to account for adherence patterns.

Significance and Impact Current guidelines for diabetes management prioritize cardiovascular and renal protection. This study aims to expand the clinical evidence base by:

• Providing actionable Real-World Evidence (RWE) on the long-term cancer-related outcomes of diabetes medications.
• Evaluating whether the choice of antidiabetic agents can serve as a strategy for lung cancer prevention in high-risk groups (COPD-T2DM).
• Contributing to the development of comprehensive treatment guidelines that consider cancer prevention alongside metabolic, cardiac, and renal health.

Abbreviation:

COPD, Chronic Obstructive Pulmonary Disease; DPP-4, Dipeptidyl Peptidase-4; ICD-10, International Classification of Diseases, 10th Revision; ICS, Inhaled Corticosteroids; ITT, Intention-To-Treat; LABA, Long-Acting Beta-2 Agonists; LAMA, Long-Acting Muscarinic Antagonists; RWD, Real-World Data; RWE, Real-World Evidence; SABA, Short-Acting Beta-2 Agonists; SAMA, Short-Acting Muscarinic Antagonists; SGLT2, Sodium-Glucose Cotransporter-2; SU, Sulfonylurea; T2DM, Type 2 Diabetes Mellitus;

• Study Type: Observational
• Enrollment (Actual): 21692

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study included adults aged ≥40 years with a prior history of COPD (screened from 2009) and newly diagnosed type 2 diabetes who initiated treatment with either sulfonylureas or SGLT2 inhibitors between January 1, 2014, and December 31, 2023. Type 2 diabetes was defined as having two or more diagnosis records within one year using ICD-10 codes E10-E14. COPD was defined by the presence of ICD-10 codes J43 or J44 (excluding J43.0) concurrent with the prescription of COPD medications at least twice within a year; these medications included long-acting muscarinic antagonists (LAMA), long-acting beta-2 agonists (LABA), ICS plus LABA, short-acting muscarinic antagonists (SAMA), short-acting beta-2 agonists (SABA), SAMA plus SABA, methylxanthines, and systemic beta agonists.

In the sensitivity analysis, we are planning to substitute sulfonylurea to DPP4 inhibitors.

Description

Inclusion Criteria:

• Adults aged ≥40 years with prior COPD (from 2009) and newly diagnosed diabetes who initiated SU or SGLT2i between January 1, 2014 and December 31, 2023

Exclusion Criteria:

• Pre-existing
• ESRD
• Cancer
• Concurrent prescribing of the study drugs at the index date
• Exposure to the drugs of interest during the year preceding the index date
• Death or cancer incidence within a month

In the sensitivity analysis, we are planning to substitute sulfonylurea to DPP4 inhibitors.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment group (main); Users of SGLT2 inhibitors (for ITT analysis)	Drug: SGLT2 inhibitor; Any new prescription of SGLT2 inhibitors after new onset of T2DM
Active control group (main); Users of sulfonylureas for ITT analysis	Drug: Sulfonylureas (SU); Any new prescription of sulfonylureas after new onset of T2DM
Treatment group (S1); Users of SGLT2 inhibitors (for ITT analysis)	Drug: SGLT2 inhibitor; Any new prescription of SGLT2 inhibitors after new onset of T2DM
Active control group (S1); Users of DPP4 inhibitors (for ITT analysis)	Drug: Sulfonylureas (SU); Any new prescription of sulfonylureas after new onset of T2DM
Treatment group (S2); Users of SGLT2 inhibitors (for as-treated analysis)	Drug: SGLT2 inhibitor; Any new prescription of SGLT2 inhibitors after new onset of T2DM
Active control group (S2); Users of sulfonylureas (for as-treated analysis)	Drug: DPP4 inhibitors; Any new prescription of DPP4 inhibitors after new onset of T2DM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung cancer	ICD-10 code (C33 or C34) and code for special purposes (V193)	From index date + 30 days to the end of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
COPD exacerbation	COPD (J43 or J44, not J43.0) and antibiotics or steroids prescription and (emergency department or admission)	From index date + 30 days to the end of follow-up
Any cancer	ICD-10 code ('C' code) and code for special purposes (V193)	From index date + 30 days to the end of follow-up

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: December 28, 2025
• First Submitted That Met QC Criteria: December 28, 2025
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Actual): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Lung cancer; Sulfonylurea; SGLT2 inhibitor; T2DM with COPD
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Chronic Disease; Disease Attributes; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Lung Diseases, Obstructive; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Pulmonary Disease, Chronic Obstructive; Lung Neoplasms; Diabetes Mellitus, Type 2; Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Protease Inhibitors; Enzyme Inhibitors; Sulfur Compounds; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Amides; Sulfones; Urea; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Sulfonylurea Compounds
• Other Study ID Numbers: SU vs. SGLT2 in T2DM with COPD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No