Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes

Effectiveness of Empagliflozin Added to Automated Insulin Delivery (AID) Systems in Adults With Type 1 Diabetes With Sub-optimal Glycemic Outcomes: a Randomized Controlled Parallel Trial

The goal of this 26-week multicenter, randomized, parallel, placebo-controlled trial is to test the effectiveness of empagliflozin use in conjunction with automated insulin delivery (AID) to improve glucose control in individuals with type 1 diabetes who do not meet target recommendations for time in range (3.9-10.0 mmol/L). The main question it aims to answer is:

- Will use of empagliflozin (2.5 mg/day) increase time spent in the target range of 3.9 to 10.0 mmol/L compared to placebo for individuals on an AID system who do not meet glycemic targets?

Participants will either take 2.5 mg of empagliflozin or a placebo daily for 26 weeks while remaining on their current AID system.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Empagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Adelyn Moore; Phone Number: (438) 866-4807; Email: adelyn.moore@mail.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre
      • Contact: Adelyn Moore; Phone Number: 4388664807; Email: adelyn.moore@mail.mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals ≥ 18 years of age.
• A clinical diagnosis of type 1 diabetes for at least one year, as per the investigators' clinical judgment (confirmatory C-peptide and antibodies will not be required).
• Minimum 3-month use of a commercial advanced AID system.
• Time in range (3.9 to 10.0 mmol/L) < 70% on their personal AID system in the 30 days prior to screening (with minimum 70% time spent in closed-loop mode).
• Agreement to use a highly effective method of birth control for individuals of child-bearing age and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche who have not reached menopause and who do not have a disclosed medical condition causing sterility (ex: hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause.

Exclusion Criteria:

• Current or ≤ 2 week use of any anti-hyperglycemic agent other than insulin (such as SGTL2i).
• Current or ≤ 1 month use of Glucagon-like Peptide 1 (GLP1)-Receptor Agonists.
• Current or ≤ 1 month use of supraphysiological doses of oral or intravenous glucocorticoids.
• Planned or ongoing very low carbohydrate diet (< 50g/day).
• Glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as per CKD-EPI formula with creatinine levels measured within the last 12 months.
• Use of hydroxyurea.
• Planned or ongoing pregnancy.
• Breastfeeding.
• Ongoing active risk of recurrent genito-urinary infections, as per the clinical judgement of the investigators.
• Severe hypoglycemic episode within 1 month of screening, defined as an event resulting in seizure, loss of consciousness, or need to present to the emergency department.
• Diabetic ketoacidosis within 6 months of screening, defined as an event requiring the need to present to medical attention and administration of intravenous insulin.
• Any serious medical illness likely to interfere with the ability to complete the trial per the judgment of the investigators.
• Clinically significant retinopathy as judged by the investigator.
• Recent (< 3 months) acute macrovascular event (ex: acute coronary syndrome or cardiac surgery).
• Prior serious reaction to SGLT2i.
• Use of the Medtronic 670G or 770G system in the last 30 days.
• In the opinion of the investigator, inability to observe the contraindications of the study drugs, or failure to comply to the study protocol or research team's recommendations (e.g., changing pump parameters, ketone measurements).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin 2.5 mg daily; Empagliflozin is a sodium/glucose cotransporter 2 inhibitor (SGLT2i) that inhibits glucose reabsorption in the kidney. In this study, a capsule of empagliflozin 2.5 mg will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.	Drug: Empagliflozin; 26-week use of automated insulin delivery system with empagliflozin (2.5 mg daily) in individuals with suboptimal time in range.
Active Comparator: Placebo; As a control, a placebo capsule will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.	Drug: Placebo; 26-week use of automated insulin delivery system with placebo (daily) in individuals with suboptimal time in range.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time of glucose levels spent in the target range (empagliflozin vs placebo)	Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on an automated insulin delivery system vs empagliflozin (2.5 mg) on an automated insulin delivery system. Percent measured as per continuous glucose monitor (CGM) data.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time spent in the glucose range between 3.9 and 7.8 mmol/L	Percent as per CGM data	4 weeks
Percentage of time spent in the glucose range below 3.9 mmol/L and 3.0 mmol/L	Percent as per CGM data	4 weeks
Percentage of time spent in the glucose range above 10.0 mmol/L and 13.9 mmol/L	Percent as per CGM data	4 weeks
Mean glucose levels	Defined as per CGM data, in mmol/L	4 weeks
Standard deviation of glucose levels	Defined as per CGM data, in mmol/L	4 weeks
Coefficient of variance of glucose levels	Percent as per CGM data	4 weeks
Total insulin delivery (overall, basal, and bolus)	Defined as per participant's pump data	4 weeks
Mean daily carbohydrate intake	Defined as per participant's pump data	4 weeks
HbA1c	Percent as per blood test	26 weeks
Estimated glomerular filtration rate (eGFR)	mL/min/1.73 m^2 as per blood test	26 weeks
Lipid profile	Includes measurements in mmol/L as per blood test: total cholesterol, triglycerides, HDL-C, LDL-C, nonHDL-C	26 weeks
Brain Natriuretic Peptide (NT-pro-BNP)	ng/L as per blood test	26 weeks
Liver profile - bilirubin	umol/L as per blood test	26 weeks
Liver profile - alanine transaminase (ALT) and alkaline phosphatase (ALP)	U/L as per blood test	26 weeks
Measurement of body mass: weight and height	Body measurement as described (weight in kilograms and height in meters). Weight and height will be combined to report body mass index in kg/m^2.	26 weeks
Waist and hip circumference, and waist-to-hip ratio	Body measurements as described (waist and hip circumference in centimeters). Waist and hip cirumference will be combined to report waist-to-hip ratio.	26 weeks
Heart rate	Body measurement as described (beats per minutes)	26 weeks
Blood pressure	Body measurement as described (diastolic and systolic pressure; mmHg)	26 weeks
Average scores between interventions based on Type 1 Diabetes Distress Scale Questionnaire	Self-report scale (1 min = "not a problem" to 6 max = "a very serious problem") that assesses a participant's distress surrounding their diabetes with higher scores correlating to higher distress.	26 weeks
Average scores between interventions based on Hypoglycemic Fear Survey - II	Likert scale (1 min to 5 max) that assesses a participant's worry surrounding hypoglycemia with higher scores indicating increased fear of hypoglycemia.	26 weeks
Average scores between interventions based on Diabetes Treatment Satisfaction Questionnaire	Self-report scale (0 min = "very dissatisfied" to 6 max = "very satisfied") that assesses a participant's satisfaction surrounding the treatment for their diabetes with higher scores indicating greater satisfaction with treatment.	26 weeks
Fasting ketone levels	As per ketone test strip and meter; measured by participant	7 days

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Diabetes Canada
• Investigators: Principal Investigator: Melissa-Rosina Pasqua, MD, Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: diabetes; empagliflozin; 26-week
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 2024-9953

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The raw data (that is, insulin delivery, glucose levels and individual participant data) and informed consent form will be shared by the corresponding author, for academic purposes, subject to a material transfer agreement and approval of the McGill University Health Center's Research Ethics Board. All data shared will be de-identified. Raw data will be shared for non-commercial use upon reasonable request and a material transfer agreement.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

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