Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

Type 2 diabetes (T2D) is an epidemic that afflicts more than 350 million people world-wide. Despite the use of existing medical therapies, T2D continues to cause significant morbidity and mortality, leading to large societal and financial costs to Canadians. Newer agents called sodium glucose co-transporter-2 inhibitors (SGLT2i) have been developed to improve glycemic control and lower hemoglobin A1c by increasing glycosuria. SGLT2i also reduce blood pressure and albuminuria in T2D - possibly through natriuresis. Importantly, a landmark trial "EMPA-REG OUTCOME" demonstrated that the SGLT2i empagliflozin is the first anti- hyperglycemic agent to reduce mortality and heart failure (HF) risk, and also to decrease the risk of progressive diabetic nephropathy. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a subcutaneous drug, used for treating T2D patients. Recently, this drug was also able to reduce cardiovascular endpoints in the LEADER trial. Furthermore, liraglutide attenuated the risk of progressive albuminuria as well. GLP-1RAs induce natriuretic effects, but have not been shown to reduce HF risk. Their positive cardiovascular effects are probably due to reduction in atherosclerotic events. T2D patients are at high risk for development of both HF and atherosclerotic diseases. Given that SGLT2i and GLP-1RA seem to reduce cardiovascular outcomes via different approaches, combining these two agents in the treatment of T2D is an appealing new strategy. In this project, we aim to combine GLP-1RA and SGLT2i therapies in T2D patients without HF and compare renal and cardiovascular physiological measures in these patients, such as renal function, neurohormonal activation, blood pressure, arterial stiffness, and systemic vascular resistance. This could give a better understanding on the action of the combination therapy in T2D, support future mechanist trials with patients with HF, and give support to the development of large clinical trials on this topic. Study design: Open-label, exploratory, randomized (with randomization concealment), pilot mechanistic trial, with two groups and 2 sequential treatments within each group. Study population: Male and female subjects with T2D, 18 years old or older, with eGFR ≥30 mL/min/1.73m2, as described in the full protocol. Intervention: 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). Primary Objective: Comparison of proximal tubular natriuresis (measured by FENa+, fractional excretion of sodium) after 6 weeks of SGLT2i monotherapy vs FENa+ after 6 weeks of combination therapy (SGLT2i + GLP-1RA) AND comparison of FENa+ after 6 weeks of GLP1-RA monotherapy vs FENa+ after 6 weeks of combination therapy (GLP-1RA + SGLT2i). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients visit the outpatient clinic on a more regular basis than standard patient care - i.e. at study inclusion and at each study visit for clinical assessment. Blood work for physiological assessments, renal function tests and cardiovascular assessments will be obtained as described in the protocol. 24hr urine will be collected one day prior to the hospital visit. No other invasive measurements will be executed. Patients receive restitution of all travel costs and also a financial aid for 3 visits. Patients receive no priority in treatment of other diseases in the clinic during this study. There are no other direct benefits for the patients to be included and participation is on a voluntary basis. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04535960
Study type Interventional
Source University Health Network, Toronto
Contact Vesta Lai, RN
Phone 416-340-4800
Email vesta.lai@uhn.ca
Status Recruiting
Phase Phase 2
Start date January 24, 2019
Completion date October 2023

See also
  Status Clinical Trial Phase
Completed NCT02771093 - An Exploratory Study of the Effects of Trelagliptin and Alogliptin on Glucose Variability in Patients With Type 2 Diabetes Mellitus Phase 4
Completed NCT02545842 - Assessment Study of Three Different Fasting Plasma Glucose Targets in Chinese Patients With Type 2 Diabetes Mellitus (BEYOND III/FPG GOAL) Phase 4
Recruiting NCT03436212 - Real-Life Home Glucose Monitoring Over 14 Days in T2D Patients With Intensified Therapy Using Insulin Pump. N/A
Completed NCT03244800 - A Study to Investigate Different Doses of 0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus. Phase 2
Completed NCT03960424 - Diabetes Management Program for Hispanic/Latino N/A
Withdrawn NCT02769091 - A Study in Adult Patients With Nonalcoholic Steatohepatitis Who Also Have Type 2 Diabetes Phase 2
Recruiting NCT06065540 - A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor Phase 3
Recruiting NCT05008276 - Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress (PANTHER Study)
Completed NCT04091373 - A Study Investigating the Pharmacokinetics of a Single Dose Administration of Cotadutide Phase 1
Completed NCT03296800 - Study to Evaluate Effects of Probenecid, Rifampin and Verapamil on Bexagliflozin in Healthy Subjects Phase 1
Recruiting NCT06212778 - Relationship Between Nutritional Status, Hand Grip Strength, and Fatigue in Hospitalized Older Adults With Type 2 Diabetes Mellitus.
Completed NCT05979519 - Fresh Carts for Mom's to Improve Food Security and Glucose Management N/A
Recruiting NCT05579314 - XW014 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus (T2DM) Phase 1
Completed NCT03859934 - Metabolic Effects of Melatonin Treatment Phase 1
Terminated NCT03684642 - Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Phase 3
Completed NCT03248401 - Effect of Cilostazol on Carotid Atherosclerosis Estimated by 3D Ultrasound in Patients With Type 2 Diabetes Phase 4
Completed NCT03644134 - A Personalized Intervention to Manage Physiological Stress and Improve Sleep Patterns N/A
Completed NCT05295160 - Fasting-Associated Immune-metabolic Remission of Diabetes N/A
Completed NCT02836873 - Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment Phase 3
Completed NCT02226003 - Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017) Phase 3