Sodium-glucose Co-transporter 2 Inhibitors and the Risk of Early Bladder Cancer Events

Saturday, August 27, 2022

2:00 PM – 2:15 PM CEST

Location: Congress Hall D5

Publication Number: 167

Background: SGLT2 inhibitors (SGLT2i) are a recently marketed pharmacotherapy for the treatment of type 2 diabetes. While this drug class was shown to reduce the risk of cardiovascular and mortality events in cardiovascular outcome trials, their safety profile is not fully characterized. Some trials have reported small imbalances in newly diagnosed bladder cancer in users of SGLT2i, all of which occurred shortly after randomization. To date, the potential association between use of SGLT-2i and bladder cancer incidence has not been investigated in the real-world setting.

Objectives: The objective of this multi-site population-based cohort study is to determine whether use of SGLT2i, when compared with use of other second-to-third line antidiabetic drugs, [GLP-1 receptor agonists (GLP1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i)], is associated with an increase in the short-term risk of incident bladder cancer among patients with type 2 diabetes.

Methods: To address this safety concern, we used three US healthcare claims databases (Optum Clinformatics, IBM MarketScan, Medicare fee-for-service) and a UK electronic health record database (Clinical Practice Research Datalink) to assemble cohorts of adults with type 2 diabetes. We identified initiators of SGLT2i (n=453,726) or GLP1RA (n=375,990) (comparison #1), and SGLT2i (n=347,055) or DPP4i (n=854,141) (comparison #2) from January 2013 through December 2020 and followed patients using an intention to treat exposure definition. Propensity score (PS) based fine stratification was used to balance the cohort characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for bladder cancer in each database using Cox proportional hazards models and results were pooled using random-effect models with inverse variance.

Results: After PS based fine stratification, the characteristics of the cohorts were balanced, with a median age of 61 years and 45% female patients. After a median range of follow-up of 1.5 to 2.2 years, the use of SGLT2i was not associated with the risk of bladder cancer, compared to the use of GLP1RA (HR=0.90; 95% CI: 0.81-1.00). This association was not modified by age, sex or a history of urogenital infection. Compared to the use of DPP4i, SGLT2i are not associated with bladder cancer incidence (HR=0.99; 95% CI: 0.91-1.09) after a median range of follow-up of 1.6 to 2.6 years. The results remained consistent when restricting the outcome to malignant cancers and using fixed-effects models for pooling.

Conclusions: Overall, the results of this large international cohort study provide reassurance on the short-term effects of SGLT2is on bladder cancer incidence.

Presenting Author(s)

DA

Devin Abrahami, PhD

Research Fellow
Brigham and Women's Hospital, Harvard Medical School
Boston, Massachusetts, United States

Slides

Co-Author(s)

HT

Helen Tesfaye

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States
HY

Hui Yin, MSc

The Lady Davis Research Institute, Centre for Clinical Epidemiology, Jewish General Hospital, QC, Canada, QC, Canada
SV

Seanna Vine

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States
BH

Blánaid Hicks

Lecturer
Queen’s University Belfast, Belfast, Northern Ireland, United Kingdom
OY

Oriana Yu

Division of Endocrinology, Jewish General Hospital, Montreal, Québec, Canada, Canada
RP

Robert W. Platt, PhD

Professor
McGill Dept of Epidemiology, Biostatistics and Occupational Health
Montreal, Quebec, Canada
Sebastian Schneeweiss, ScD, MD, FISPE

Professor of Medicine
BWH Div of Pharmacoepidemiology and Pharmacoeconomics
Boston, Massachusetts, United States
EP

Elisabetta Patorno

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States
LA

Laurent Azoulay, PhD

Associate Professor
McGill University, Montreal, Quebec, Canada, QC, Canada