Chronic Kidney Diseases, Type 2 Diabetes
Conditions
Brief summary
The goal of this study is to test whether a dipeptidyl peptidase-4 inhibitor, compared with a sulfonylurea, improves time in normal blood glucose range and reduces blood glucose variability. Blood glucose is measured using a continuous glucose monitoring device.
Detailed description
This is a proof-of-concept clinical trial testing the effects of linagliptin versus glipizide on glucose variability among people with type 2 diabetes and stage 3-4 CKD. In a cross-over design, each enrolled participant will receive 28 days of each study medication. Study medications will be provided in a randomly assigned order without blinding. The primary study outcome is glucose time in range, measured by blinded continuous glucose monitoring for the last 6 days of each 28-day treatment period. Secondary outcomes include indices of glycemic variability, hypoglycemia, and biomarkers of systemic inflammation, oxidative stress, and albuminuria. The overall goal of this research is to identify safe and effective treatments to control glycemia among patients with diabetes and CKD.
Interventions
DRUGLinagliptin
Receives 4 weeks of study drug linagliptin
DRUGGlipizide
Receives 4 weeks of study drug glipizide
Sponsors
American Diabetes Association
Medtronic
Abbott
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * eGFR 15-59 mL/min/1.73 m2 * Hemoglobin A1c \< 8% * Age ≥ 18 years * Current use of sulfonylurea
Exclusion criteria
* BMI \> 40 kg/m2 * Actively using CGM for clinical care * End stage renal disease needing dialysis * Kidney transplant * Pregnant or nursing * Unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Time in Range | last 6 days of each 28-day treatment period | Time with glucose 70-140 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Variability | last 6 days of each 28-day treatment period | SD of glucose readings |
| Hypoglycemia | last 6 days of each 28-day treatment period | Glucose \<70 mg/dL for at least 10 minutes |
| Biomarkers of Systemic Inflammation | last 6 days of each 28-day treatment period | Measured by plasma C-reactive protein (CRP) |
| Biomarkers of Oxidative Stress | last 6 days of each 28-day treatment period | Measured by plasma F2-isoprostanes |
| Biomarkers of Albuminuria | last 6 days of each 28-day treatment period | Measured by albumin-creatinine ratio |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Linagliptin/Glipizide Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide
Linagliptin: Receives 4 weeks of study drug linagliptin
Glipizide: Receives 4 weeks of study drug glipizide | 2 |
| Glipizide/Linagliptin Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin
Linagliptin: Receives 4 weeks of study drug linagliptin
Glipizide: Receives 4 weeks of study drug glipizide | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Linagliptin/Glipizide | Glipizide/Linagliptin | Total |
|---|---|---|---|
| Age, Continuous | 67.3 years STANDARD_DEVIATION 9.9 | 70.4 years | 68.3 years STANDARD_DEVIATION 7.2 |
| Race/Ethnicity, Customized Non-Hispanic white race/ethnicity | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 0 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Glucose Time in Range
Time with glucose 70-140 mg/dL
Time frame: last 6 days of each 28-day treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide | Glucose Time in Range | 495.2 minutes per day | Standard Deviation 671.9 |
| Linagliptin | Glucose Time in Range | 573.3 minutes per day | Standard Deviation 669.1 |
Secondary
Biomarkers of Albuminuria
Measured by albumin-creatinine ratio
Time frame: last 6 days of each 28-day treatment period
Population: Labs not run due to small sample size.
Secondary
Biomarkers of Oxidative Stress
Measured by plasma F2-isoprostanes
Time frame: last 6 days of each 28-day treatment period
Population: Labs not run due to small sample size.
Secondary
Biomarkers of Oxidative Stress
Measured by urine F2-isoprostanes
Time frame: last 6 days of each 28-day treatment period
Population: Labs not run due to small sample size.
Secondary
Biomarkers of Systemic Inflammation
Measured by plasma C-reactive protein (CRP)
Time frame: last 6 days of each 28-day treatment period
Population: Labs not run due to small sample size.
Secondary
Biomarkers of Systemic Inflammation
Measured by plasma interleukin-6
Time frame: last 6 days of each 28-day treatment period
Population: Labs not run due to small sample size.
Secondary
Glycemic Variability
SD of glucose readings
Time frame: last 6 days of each 28-day treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glipizide | Glycemic Variability | 40.9 mg/dL | Standard Deviation 16.1 |
| Linagliptin | Glycemic Variability | 41.5 mg/dL | Standard Deviation 22.7 |
Secondary
Hypoglycemia
Glucose \<70 mg/dL for at least 10 minutes
Time frame: last 6 days of each 28-day treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glipizide | Hypoglycemia | 4 events |
| Linagliptin | Hypoglycemia | 2 events |