Basal Plus GLP1-ra on Glycemic Variability in CKD

Effect of Glucagon-like Peptide 1 Receptor Agonist in Combination with Insulin on Glycaemic Variability and Time-in-range in Diabetic Kidney Disease: a Randomised Controlled Trial

To compare GLP-1 RA plus basal insulin (BGLP) versus basal-bolus (BB) insulin regimens on glycemic variability (GV) and time in range (TIR) in diabetes patients CKD stage 3-4

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetic Kidney Disease
• Intervention / Treatment: Drug: Dulaglutide; Drug: Insulin Degludec; Device: Continuous glucose monitor

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Type 2 diabetes mellitus diagnosed for at least 6 months
2. Male or female age ≥ 18 years old and ≤ 75 years old.
3. Body mass index between 18 and 40 kg/m2 inclusive
4. HbA1c ≥ 6.5% and ≤ 9.0% at screening
5. Women who are not pregnant, lactating or planning a pregnancy during their participation in the clinical study.
6. Patients with CKD stage 3 or 4 as defined by estimated glomerular filtration rate between 15-59 ml/min/m2 by the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening
7. Willingness, ability and commitment to comply with the testing, procedure and follow-up outlined in this protocol including (but not limited to) and use of pre-specified glucose monitoring devices.
8. In the opinion of the investigator, absence of any physical limitations, addictive diseases, or underlying medical conditions (including mental health) that may preclude the patient from being a suitable study candidate.
9. Written informed consent to participate in the study provided by the patient.
10. Willing and capable of use of a continuous glucose monitor as judged by the investigator

Exclusion Criteria:

1. Type 1 diabetes
2. Currently pregnant, as demonstrated by a positive pregnancy test at screening or planning pregnancy
3. Treatment with GLP-1 RA or insulin degludec in the past three months
4. Any active acute or chronic disease or condition that, in the opinion of the investigator, might interfere with the performance of this study.
5. Any active acute or chronic infectious disease that, in the opinion of the investigator, would pose an excessive risk to study staff.
6. Current use or recent exposure to any medication that in the opinion of the investigator could have an influence on the patient's ability to participate in this study or on the performance of the test device.
7. Extensive skin changes/diseases that preclude wearing the CGM on normal skin at the proposed application sites (e.g., extensive psoriasis, recent burns or severe sunburn, extensive eczema, extensive scarring, extensive tattoos, dermatitis herpetiformis).
8. Have a known allergy to medical-grade adhesives
9. Known current or recent alcohol or drug abuse
10. Diabetic ketoacidosis, hyperosmolar hyperglycaemic state or myocardial infarction in the six months prior to screening
11. Patients on renal replacement therapy or likely require kidney transplant or dialysis during the study period
12. Currently participating in another investigational study protocol where the testing or results may interfere with study compliance, diagnostic results, or data collection.
13. An identified protected vulnerable patient (including but not limited to those in detention, or a prisoner).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLP1-ra plus basal insulin (BGLP); Dulaglutide and insulin degludec in combination with CGM	Drug: Dulaglutide; Dulaglutide once weekly subcutaneous; Drug: Insulin Degludec; Insulin degludec once daily; Device: Continuous glucose monitor; Dexcom G6 CGM system
Active Comparator: Basal bolus insulin (BB); Insulin aspart/lispro and insulin degludec in combination with CGM	Drug: Insulin Degludec; Insulin degludec once daily; Device: Continuous glucose monitor; Dexcom G6 CGM system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability	% coefficient of variation on blinded CGM	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percent time in range	percent time 3.9-10 mmol/l on CGM	week 16 and 26
percent time below range	percent time below 3.9 mmol/l and below 3.0 mmol/l	week 16 and 26
percent time above range	percent time above 10 mmol/l and 13.9 mmol/l	week 16 and 26
HbA1c	HbA1c	week 16 and 26
Self reported hypoglycemia	level 1,2 and 3 hypoglycemia, biochemically confirmed	26 weeks
Self monitored glucose profiles	Fasting and postprandial	26 weeks
Body weight	Body weight	week 16 and 26
Insulin doses	Insulin doses	week 16 and 26
eGFR	estimated glomerular filrate rate by CKD-EPI equation	week 16 and 26
uACR	urine albumin creatinine ratio	week 16 and 26
Diabetes Treatment Satisfaction	Chinese version of Diabetes Treatment Satisfaction Questionnaire, higher score better	week 16 and 26

Collaborators and Investigators

• Sponsor: Elaine Chow

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Actual): October 30, 2024
• Study Completion (Actual): October 30, 2024

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 29, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Diabetes Mellitus; Diabetes Complications; Kidney Diseases; Diabetic Nephropathies; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Dulaglutide
• Other Study ID Numbers: BGLP-DKD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes