Basal Plus GLP1-ra on Glycemic Variability in CKD

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Diabetes Mellitus, Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Dulaglutide
* Drug: Insulin Degludec
* Device: Continuous glucose monitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus diagnosed for at least 6 months Male or female age ≥ 18 years old and ≤ 75 years old. Body mass index between 18 and 40 kg/m2 inclusive HbA1c ≥ 6.5% and ≤ 9.0% at screening Women who are not pregnant, lactating or planning a pregnancy during their participation in the clinical study. 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 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. 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. Written informed consent to participate in the study provided by the patient. Willing and capable of use of a continuous glucose monitor as judged by the investigator Exclusion Criteria: Type 1 diabetes Currently pregnant, as demonstrated by a positive pregnancy test at screening or planning pregnancy Treatment with GLP-1 RA or insulin degludec in the past three months Any active acute or chronic disease or condition that, in the opinion of the investigator, might interfere with the performance of this study. Any active acute or chronic infectious disease that, in the opinion of the investigator, would pose an excessive risk to study staff. 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. 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). Have a known allergy to medical-grade adhesives Known current or recent alcohol or drug abuse Diabetic ketoacidosis, hyperosmolar hyperglycaemic state or myocardial infarction in the six months prior to screening Patients on renal replacement therapy or likely require kidney transplant or dialysis during the study period Currently participating in another investigational study protocol where the testing or results may interfere with study compliance, diagnostic results, or data collection. An identified protected vulnerable patient (including but not limited to those in detention, or a prisoner).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |