Acute pancreatitis risk in type 2 diabetes patients treated with canagliflozin versus other antihyperglycemic agents: an observational claims database study

Abstract

Objective: Observational evidence suggests that patients with type 2 diabetes mellitus (T2DM) are at increased risk for acute pancreatitis (AP) versus those without T2DM. A small number of AP events were reported in clinical trials of the sodium glucose co-transporter 2 inhibitor canagliflozin, though no imbalances were observed between treatment groups. This observational study evaluated risk of AP among new users of canagliflozin compared with new users of six classes of other antihyperglycemic agents (AHAs).

Methods: Three US claims databases were analyzed based on a prespecified protocol approved by the European Medicines Agency. Propensity score adjustment controlled for imbalances in baseline covariates. Cox regression models estimated the hazard ratio of AP with canagliflozin compared with other AHAs using on-treatment (primary) and intent-to-treat approaches. Sensitivity analyses assessed robustness of findings.

Results: Across the three databases, there were between 12,023–80,986 new users of canagliflozin; the unadjusted incidence rates of AP (per 1000 person-years) were between 1.5–2.2 for canagliflozin and 1.1–6.6 for other AHAs. The risk of AP was generally similar for new users of canagliflozin compared with new users of glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sulfonylureas, thiazolidinediones, insulin, and other AHAs, with no consistent between-treatment differences observed across databases. Intent-to-treat and sensitivity analysis findings were qualitatively consistent with on-treatment findings.

Conclusions: In this large observational study, incidence rates of AP in patients with T2DM treated with canagliflozin or other AHAs were generally similar, with no evidence suggesting that canagliflozin is associated with increased risk of AP compared with other AHAs.

Keywords:

• Acute pancreatitis
• canagliflozin
• type 2 diabetes
• observational study

Notes

Transparency

Declaration of funding

This study was supported by Janssen Research & Development, LLC, which was involved in the study design, analysis, and interpretation of data and in the decision to publish. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation.

Declaration of financial/other relationships

ZY, FD, LW, LH, JW, JNS, AF, PR, MS, RQ, JY, and NR are full-time employees of Janssen Research & Development, LLC. GM was a full-time employee of Janssen Research & Development, LLC when the study was carried out. JAB is a full-time employee of Johnson & Johnson. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

Medical writing support was provided by Dana Tabor, PhD, of MedErgy, and was funded by Janssen Global Services, LLC.

Author contributions

All authors were involved in the study design and analysis and interpretation of the data, and drafting the manuscript or revising it critically for intellectual content. All authors have approved the final manuscript for submission, and agree to be accountable for all aspects of the work.

Data availability

All results have been made publicly available through an interactive web-based application at http://data.ohdsi.org/Sglt2iAcutePancreatitis/.

Notes

i IBM MarketScan Commercial Database (CCAE) is a registered trademark of IBM Watson Health, Ann Arbor, MI, USA.

ii IBM MarketScan Medicare Supplemental Database (MDCR) is a registered trademark of IBM Watson Health, Ann Arbor, MI, USA.

iii Optum De-identified Clinformatics Data Mart Database is a registered trademark of OptumInsight, Eden Prairie, MN, USA.