A Study Using Medical Records of Danish People With Type 2 Diabetes Comparing Empagliflozin and Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) in the Occurrence of Serious Cardiovascular Outcomes

NCT03993132 | Completed Results

• 1 other identifier: 1245-0194
• Study Type: observational
• Target: 26,774
• Locations: 1 country
• Sites: 1

Brief Summary

The primary research question is to evaluate whether, among patients with type 2 diabetes mellitus (T2D), initiation of empagliflozin changes the adjusted incidence of outcomes compared with initiation of Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA).

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - OT Analysis

  Composite outcome includes: All-cause death, acute admission with non-fatal (within 30 days) stroke, with non-fatal (within 30 days) myocardial infarction (MI), admission with unstable angina, coronary revascularization, or acute admission with non-fatal heart failure (HF). The results from on-treatment (OT) analysis are reported. For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added. In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

• Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - ITT Analysis

  Composite outcome includes: All-cause death, acute admission with non-fatal (within 30 days) stroke, with non-fatal (within 30 days) myocardial infarction (MI), admission with unstable angina, coronary revascularization, or acute admission with non-fatal heart failure (HF). The results from intention-to-treat (ITT) analysis are reported. For the ITT analyses, participants were defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

Secondary Outcomes (12)

• Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - OT Analysis

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

• Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - ITT Analysis

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

• Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - OT Analysis

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

• Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - ITT Analysis

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

• Incidence Rate of All-cause Hospitalization or Death - OT Analysis

  From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

Study Arms (1)

Patients with type 2 diabetes

Drug: Empagliflozin; Drug: Liraglutide

Interventions

Empagliflozin DRUG

new users (initiators) of Empagliflozin

Patients with type 2 diabetes

Liraglutide DRUG

initiators of Liraglutide

Patients with type 2 diabetes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The source population for our study consists of individuals with type 2 diabetes, who are defined in our study as individuals who live in Denmark and who have never used oral antihyperglycemic drugs or insulin.

You may qualify if:

• The empagliflozin-exposed population must also meet the following criteria:
• Have at least one prescription for empagliflozin or fixed-dose combination of empagliflozin with another drug, with or without treatment with another glucose-lowering drug
• Have no prescription/dispensing of SGLT2 inhibitors (including empagliflozin) alone or in fixed-dose combination prior to the index date
• Have no prescription/dispensing of a GLP-1 receptor agonist alone or in fixed dose combination prior to the index date
• The population exposed to GLP1-RA must meet the following criteria:
• Have at least one prescription for GLP1-RA or a fixed-dose combination of GLP1-RA with another drug, with or without treatment with another glucose-lowering drug.
• Have no prescription/dispensing of a GLP-1 receptor agonist alone or in fixed dose combination prior to the index date
• Have no prescription/dispensing of SGLT2 inhibitors (including empagliflozin) alone or in fixed-dose combination prior to the index date

You may not qualify if:

• Patients with type 1 diabetes T1D before the index date will not be included in the study.
• In one main analysis, we will assess co-primary and secondary outcomes among all patients, regardless of a history of previous outcome events being present or not. In other words, we will allow a previous history of CVD events. We will adjust for the history of these events in the regression model rather than excluding patients with previous events (e.g. assess outcome rates of myocardial infarction in empagliflozine and liraglutide initiators while adjusting for previous history of myocardial infarction, unstable angina, or coronary revascularization).
• In another main analysis of outcomes, we will exclude patients who had a specific outcome previously.
• For example in the analysis of the primary heart failure outcome (heart failure admission or loop-diuretics), patients will not be included if a diagnosis of heart failure is recorded any time before or at the index date, or if a prescription for loop-diuretics has been filled within 12 months before or at the index date. For the secondary outcome of acute hospital admission with heart failure, we will include also patients with previous prescription for loop-diuretics, but exclude those with previous heart failure admission.
• For analysis of stroke, patients will not be included if a diagnosis of stroke is recorded any time before or at the index date.
• For analysis of myocardial infarction, unstable angina, or coronary revascularization, patients will not be included if any of these 3 major atherosclerotic cardiovascular events are recorded any time before or at the index date.
• In additional analyses, other criteria will apply (To be discussed, RWT). Thus, an additional analysis will include also patients with previous outcome events, and adjust for the history of these events in the regression model rather than excluding them (e.g. assess outcome rates of myocardial infarction in empagliflozine and liraglutide initiators while adjusting for previous history of myocardial infarction, unstable angina, or coronary revascularization).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Department of Clinical Epidemiology - Aarhus Unversiteteshospital

Aarhus, 8200, Denmark

Location

Related Publications (1)

• Thomsen RW, Christensen LWB, Kahlert J, Knudsen JS, Ustyugova A, Sandgaard S, Holmgaard P, Ehlers LH, Sorensen HT. Healthcare Resource Utilization and Costs for Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists in Routine Clinical Care in Denmark. Diabetes Ther. 2022 Dec;13(11-12):1891-1906. doi: 10.1007/s13300-022-01323-y. Epub 2022 Oct 31.

  PMID: 36315384 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Due to a huge shift after 2018 in drug type use within the GLP-1RA group the final analysis (between 2015 - 2020) was not completed. Instead, an exploratory analysis was performed, using the initial analysis of comparing from empagliflozin versus liraglutide from 2015 to 2018 but following these same patients up to 2020.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

18002430127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 20, 2019
• Study Start: October 1, 2018
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: February 12, 2024
• Results First Posted: February 12, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)