Sodium-glucose Co-transporter 2 (SGLT2) Inhibitor Risk of Below-Knee Lower Extremity Amputation: A Retrospective Cohort Study Using a Large Claims Database in the United States

SGLT2 Inhibitor Risk of Below-Knee Lower Extremity Amputation: A Retrospective Cohort Study Using a Large Claims Database in the United States

The purpose of the study is to estimate the incidence of below-knee lower extremity amputation in type 2 diabetes mellitus (T2DM) participants newly exposed to sodium-glucose co-transporter 2 inhibitors (SGLT2i)/ non-SGLT2i antihyperglycemic agents (AHA) overall and in the subgroup with high cardiovascular (CV) risk and to compare the hazards of below-knee lower extremity amputation in canagliflozin new users versus non-SGLT2i AHA new users.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2

• Study Type: Observational
• Enrollment (Actual): 127690

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants who are new users (with at least 365 day of prior observation) to a drug exposure of interest between April 1, 2013 and January 31, 2015 and at least 1 condition occurrence of 'Type II diabetes' any time before or on index and no condition occurrences of 'Type I diabetes' or 'Secondary diabetes' any time before or on index date. January 31, 2015 reflects the data cutoff date for the initial analysis.

Description

Inclusion Criteria:

• First exposure to the particular drug in person's history
• For the initial analysis, exposure start is between April 1, 2013 and January 31, 2015. For the ongoing repeat analysis per the protocol amendment, the study period ending date will vary depending on the time of each data extraction and analysis
• At least 365 days of observation time prior to index
• At least 1 condition occurrence of 'Type II diabetes' any time before or on index
• Exactly 0 condition occurrences of 'Type I diabetes' any time before or on index

Exclusion Criteria:

• Participants who had amputations prior to the index date were excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Sodium-glucose Co-transporter 2 Inhibitors (SGLT2i) New Users; Participants will not receive any intervention as a part of this study. SGLT2i includes canagliflozin, dapagliflozin, empagliflozin as prescribed in clinical practice. Participants will be evaluated in 2 sub-cohorts (with or without high CV risk) and overall.
Canagliflozin New Users; Participants will not receive any intervention as a part of this study. This cohort contains new users of canagliflozin as prescribed in clinical practice. Participants will be evaluated in 2 risk) and overall.
Dapagliflozin New Users; Participants will not receive any intervention as a part of this study. This cohort contains new users of dapagliflozin as prescribed in clinical practice. Participants will be evaluated in 2 sub-cohorts (with or without high CV risk) and overall.
Empagliflozin New Users; Participants will not receive any intervention as a part of this study. This cohort contains new users of empagliflozin as prescribed in clinical practice. Participants will be evaluated in 2 sub-cohorts (with or without high CV risk) and overall.
First-time Non-SGLT2i AHA New Users; Participants will not receive any intervention as a part of this study. Non-SGLT2i AHA include dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, thiazolidinediones (TZDs), Sulfonylureas, Insulin, and other AHAs. Participants will be evaluated in 2 sub-cohorts (with or without high CV risk) and overall.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Below-knee Lower Extremity Amputation in Type 2 Diabetes Mellitus (T2DM) Patients Newly Exposed to Sodium-glucose Co-transporter 2 Inhibitors (SGLT2i) Overall and in the Subgroup With High Cardiovascular (CV) Risk	The occurrence of a below-knee lower extremity amputation will be defined by observing an associated procedure code in the outpatient or inpatient medical service claims.	up to 6 years (estimated study duration)
Incidence of Below-Knee Lower Extremity Amputation in T2DM Patients Newly Exposed To non-SGLT2i Aha Overall And In The Subgroup With High CV Risk	The occurrence of a below-knee lower extremity amputation will be defined by observing an associated procedure code in the outpatient or inpatient medical service claims.	up to 6 years (estimated study duration)
Incidence of Below-Knee Lower Extremity Amputation in Canagliflozin New Users Versus non-SGLT2i Aha New Users	Hazard ratio will be estimated using a conditional Cox proportional hazards model based on propensity-matched cohorts.	up to 6 years (estimated study duration)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2016
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 3, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): August 30, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: RRA-17578 (Other Identifier: Janssen Research & Development, LLC.)