Cardiovascular Outcomes SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists

Cardiovascular Outcomes of Type 2 Diabetic Patients Treated With SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists in Real-life. An Observational Study Using Clinical-administrative Data

Patients with type 2 diabetes (T2D) suffer from an excess risk of adverse cardiovascular events. Recently, two classes of glucose lowering agents, namely SGLT-2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA), have proved superior to placebo in protecting T2D patients from cardiovascular events in dedicated trials. Patient populations in such trials were mainly composed of T2D individuals with established cardiovascular disease (CVD) or at very high risk for CVD. In addition, no clinical trial has so far compared cardiovascular outcomes of T2D associated with SGLT2i versus GLP-1RA. In addition, whether different results would incur in patients at lower CVD risk is unclear. On this basis, we designed this retrospective real-world study to compare cardiovascular outcomes of patients newly treated with SGLT2i versus GLP-1RA in routine clinical practice

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: SGLT2 inhibitor; Drug: GLP-1 receptor agonist

• Study Type: Observational
• Enrollment (Actual): 10000

Contacts and Locations

Study Locations

• Italy
  • Padova, Italy, 35128
    • Division of Metabolic Diseases, University Hospital of Padova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Type 2 diabetes

Description

Inclusion Criteria:

• Italian citizens, residing in the Region
• Registered as beneficiaries for at least one year between January 1st, 2012 and September 30th, 2018
• Diagnosis of type 2 diabetes
• Newly initiating SGLT-2 inhibitors or GLP-1 receptor agonists
• Being treated with glucose lowering medications before (at least one prescription of an antidiabetic agent in ATC class A10B prior to the index date)
• Time between the index date and the last SGLT2 inhibitors or GLP-1 receptor agonists prescription shorter than 8 months,
• Follow-up time or time-to-endpoint of at least three months

Exclusion Criteria:

• Patients who started SGLT2i or GLP-1RA before 2014
• Patients with an insufficient exposure time
• Patients with an incident event within three months after the index date.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SGLT2i; Patients who received new prescription of a SGLT-2 inhibitor	Drug: SGLT2 inhibitor; New prescription of a SGLT-2 inhibitor (dapagliflozin, empagliflozin or canagliflozin) at any dosage during routine clinical practice
GLP-1RA; Patients who received new prescription of a GLP-1 receptor agonist	Drug: GLP-1 receptor agonist; New prescription of a GLP-1 receptor agonisty (exenatide, liraglutide, lixisenatide, dulaglutide) at any dosage during routine clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 point major adverse cardiovascular events (4P-MACE)	First occurrence of myocardial infarction, stroke, or death	3-26 months after index date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization for cardiovascular causes	First hospitalization for any cardiovascular cause	3-26 months after index date
Death	All-cause death	3-26 months after index date
Myocardial infarction	Myocardial infarction	3-26 months after index date
Heart failure	Hospitalization for heart failure	3-26 months after index date
Stroke	Stroke or transient ischemic attack	3-26 months after index date
Revascularization	Any arterial site revascularization (surgical or endovascular)	3-26 months after index date

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events	Occurrence of: amputation, Fournier's gangrene, bone fracture, diabetic ketoacidosis, infections, pancreatitis, pancreatic cancer, acute kidney injury	3-26 months after index date

Collaborators and Investigators

• Sponsor: University of Padova

Publications and helpful links

General Publications

• Longato E, Di Camillo B, Sparacino G, Gubian L, Avogaro A, Fadini GP. Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life. BMJ Open Diabetes Res Care. 2020 Jun;8(1):e001451. doi: 10.1136/bmjdrc-2020-001451.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2014
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ACTUAL): February 29, 2020

Study Registration Dates

• First Submitted: December 1, 2019
• First Submitted That Met QC Criteria: December 1, 2019
• First Posted (ACTUAL): December 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 8, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: DIMEDDEI3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data cannot be shared

Drug and device information, study documents

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