Incretin and Treatment With Inhibition of Sodium-glucose Cotransporter-2 Combination Insights Into Mechanisms Implicated in Congestive Heart Failure: "NATRIURETIC" Trial

NCT04535960 | Unknown Phase 2

• 1 other identifier: 18-5058
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to provide essential mechanistic insights into natriuretic and hemodynamic effects of SGLT2i and GLP-1RA agents in T2D patients. Ultimately, by obtaining physiological data in T2D patients without HF, our aims are to gain insight into how the use of this combined therapy may be used in T2D with HF in future work.

Conditions

Type 2 Diabetes Mellitus

Keywords

SGLT2 inhibition; GLP-1 receptor agonist; type 2 diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Proximal tubular natriuresis

  Measured by fractional excretion of sodium

  up to 12 weeks

Secondary Outcomes (7)

• Glomerular Filtration Rate

  Glomerular Filtration Rate (GFR, based on plasma iohexol clearance) will be measured at 2 time points: monotherapy (6 weeks) and combination therapy (12 weeks)

• Systolic blood pressure

  Systolic blood pressure (SBP) will be measured at 2 time points: monotherapy (6 weeks) and combination therapy (12 weeks)

• Body weight

  Body weight will be measured at 2 time points: monotherapy (6 weeks) and combination therapy (12 weeks)

• Arterial stiffness

  Arterial stiffness will be measured at 2 time points: monotherapy (6 weeks) and combination therapy (12 weeks)

• Systemic vascular resistance

  Systemic vascular resistance will be measured at 2 time points: monotherapy (6 weeks) and combination therapy (12 weeks)

Study Arms (2)

Liraglutide

EXPERIMENTAL

Liraglutide Subcutaneous Total Dose 1.8mg daily for 6 weeks

Drug: Empagliflozin 25 MG + Liraglutide 1.8 MG; Drug: Liraglutide 1.8 MG + Empagliflozin 25 MG

Empagliflozin

EXPERIMENTAL

Empagliflozin Tablets Total Dose 25mg daily for 6 weeks

Drug: Empagliflozin 25 MG + Liraglutide 1.8 MG; Drug: Liraglutide 1.8 MG + Empagliflozin 25 MG

Interventions

Empagliflozin 25 MG + Liraglutide 1.8 MG DRUG

Patients will be randomized to initial therapy with empagliflozin 25mg PO daily for 6 weeks. After that, patients in the empagliflozin group will also receive liraglutide 1.8mg SC daily for additional 6 weeks.

Also known as: Generic names are above, listed

Empagliflozin; Liraglutide

Liraglutide 1.8 MG + Empagliflozin 25 MG DRUG

Patients will be randomized to initial therapy with liraglutide 1.8 mg SC daily, for 6 weeks. After that, patients will also receive empagliflozin 25mg PO daily for 6 weeks.

Also known as: Generic names are above, listed

Empagliflozin; Liraglutide

Eligibility Criteria

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

You may qualify if:

• Men and women diagnosed with T2D ≥6 months prior to informed consent;
• eGFR ≥30 mL/min/1.73m2;
• Age \>18 years;
• HbA1c 7.0%-12.0%;
• Body Mass Index (BMI) 18.5-40.0 kg/m2;
• Stable HbA1c, measured 2-12 months prior to screening, within 5% of baseline value;
• Blood pressure ≤160/100 mmHg at screening, \>90/60 mmHg;
• Stable on dose of ACE inhibitor, angiotensin receptor blocker or renin inhibitor for at least 2 weeks.

You may not qualify if:

• Type 1 Diabetes;
• Leukocyte and/or nitrite positive urinalysis that is untreated;
• Severe hypoglycaemia within 2 months prior to screening;
• History of hypoglycaemia unawareness based on investigator judgement;
• Unstable coronary artery disease with acute coronary syndrome, percutaneous intervention or bypass surgery within 3 months;
• Clinically significant valvular disease subject to PI/Sub PI's discretion;
• Congestive heart failure subject to PI/Sub PI's discretion;
• Bariatric surgery or other surgeries that induce chronic malabsorption within one year;
• Anti-obesity drugs or diet regimen and unstable body weight three months prior to screening;
• Treatment with systemic corticosteroids;
• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells;
• Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control;
• Participation in another trial with an investigational drug within 30 days of informed consent;
• Alcohol or drug abuse within three months prior to informed consent that would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement;
• Liver disease, defined by serum levels of alanine transaminase, aspartate transaminase, or alkaline phosphatase \>3 x upper limit of normal as determined during screening;

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Renal Physiology Laboratory

Toronto, Ontario, Canada

RECRUITING

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

Study Officials

• David ZI Cherney, MD PhD FRCPC

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vesta Lai, RN

CONTACT

416-340-4800; vesta.lai@uhn.ca

Yuliya Lytvyn, PhD

CONTACT

julia.lytvyn@mail.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Clinician Scientist

Model Details: Patients will be randomized to initial therapy with empagliflozin 25mg PO daily or liraglutide 1.8 mg SC daily, for 6 weeks. After that, patients in the empagliflozin group will also receive liraglutide 1.8mg SC daily for additional 6 weeks and patients in the liraglutide group will also receive empagliflozin 25mg PO daily for 6 weeks (combination therapy).

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: September 2, 2020
• Study Start: January 24, 2019
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: May 17, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)