Type 2 Diabetes (T2DM)
Conditions
Keywords
Beta Cell Function, Type 2 diabetes, Black African American, Diabetes metabolism, GLP-1 receptor Agonist, SGLT-2 inhibitor, medication effects in Type 2 Diabetes
Brief summary
Minorities have higher rates of diabetes, poorer glucose control, and higher complications and mortality rates than white people. Several recently approved diabetes medicines improve cardiovascular and renal outcomes through two different mechanisms. This study will explore key determinants of blood glucose levels namely beta cell function after short-term randomized, parallel group treatment with FDA approved Glucagon-Like Peptide-1 Receptor Agonists¬ (GLP-1 RA), or FDA approved Sodium-Glucose co-Transporter-2 Inhibitor (SGLT-2i). Because diabetes in black people shows a unique ability to recover pancreatic insulin secretion, it is important to determine whether the effects of these drug classes differentially improve pancreatic beta cell function.
Detailed description
Approximately 200 black people with DM2 will be screened, then stabilized on diet and exercise alone, metformin alone or metformin plus a sulfonylurea. Following stabilization, those meeting study entry criteria will be offered the treatment study with 60 randomized to 4 months of treatment with GLP-1 RA or a SGLT-2i administered according to FDA approved guidelines. After an overnight fast, an oral glucose tolerance test (OGTT) will be completed prior to randomization and after 4 months, or at earlier study termination. Screening Visit Screening consent, medical history and physical exam (including height and weight) will be obtained, as well as baseline blood work (complete blood count, fasting glucose, A1c, lipid profile, BUN, creatinine and thyroid panel), electrocardiogram (EKG) and pregnancy test (if capable of conception). Post-screening Visits These will occur monthly with additional visits as needed and may be by telephone or in-person, as determined by patient and staff. Adverse events, report of finger stick glucose determinations will be obtained. If in-person, weight and blood glucose (optional) will be obtained. Final Screening Visit (In-person) Once stabilized, participants will be evaluated for whether they meet all study Inclusion Criteria and none of the study Exclusion Criteria. Weight, finger stick report, and adverse events will be obtained. Laboratory specimens (as above), EKG and pregnancy test will also be obtained. After explanation of the study, including its voluntary nature, those meeting study entry criteria will be asked to read and sign the study consent form and scheduled for their Randomization Visit and baseline OGTT. Randomization Visit After an over-night fast, the study's Inclusion and Exclusion Criteria will be reassessed to confirm eligibility. The 60 eligible participants will have a standard 75 mg oral glucose tolerance test (OGTT). A catheter is inserted in the forearm for the 2-3 hours with blood withdrawn through the catheter at -10 and 0 and +10, + 20, +30, +45, +60, +90 and +120 minutes. Samples will be analyzed for glucose, insulin, and C-peptide; extra blood will be stored for possible later analyses of other blood elements, such as other hormones and metabalolomics. Month 1, 2 and 3 Visits Logs of finger sticks and weight will be obtained, as well as specific queries about possible adverse events. Final Study Visit (Month 4 or earlier for premature ending of study) Finger stick log, weight, adverse events and end-study OGTT will be obtained, as at the Randomization Visit.
Interventions
DRUGSGLT-2 inhibitor
SGLT-2 inhibitors block the SGLT-2 receptor
DRUGGLP1-RA
GLP-1 RAs stimulate the GLP-1 Receptor
Sponsors
The New York Community Trust
MaryAnn Banerji
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomized to marketed SGLT-2 inhibitors including empafliflozin or dapagliflozin versus GLP-1 receptor agonists (semaglutide, liraglutide or dulaglutide). The specific member of the class will determined by insurance copberage, pharmacy availablility or patient preference.
Eligibility
Sex/Gender
ALL
Age
24 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Agrees to participate (signs and dates the informed consent) and agrees to all study procedures and conditions of the protocol. 2. Black (self-identified) patients with relatively recent onset (\< 15 years) DM2 3. aged \>= 24 years of age (adults \< age 24 years old need additional resources to consistently participate, and may have different metabolism) 4. HbA1c between 6.9% and 10%, inclusive 5. BMI \> 23 and \< 45 kg/m2, and stable body weight over 2 months 6. In good general health, as evidenced by medical history and physical examination. And not having any of the specific items of the
Exclusion criteria
. 7. Currently taking no diabetes medication or on stable doses (2 months) of metformin or metformin plus sulfonylureas without additional diabetes medication(s). 8. Ability to take and agree to taking oral medication and to self-inject 9. For persons of reproductive potential: negative pregnancy test, use of effective contraception for at least 1 month prior to screening, and agreement to use such a method during study participation, and for an additional 4 weeks after completing the use of the study drug. They will be counseled that if they wish to become pregnant, they should follow the standard practice of optimizing their blood glucose in preparation for pregnancy. Use of these study drugs are not considered standard of care for diabetes during pregnancy. Effective contraception includes tubal ligation, hysterectomy, oral, implanted or injected contraceptives, mechanical (IUD) and barriers (diaphragm, condoms, spermicides) methods. 10. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout the study, including following a diabetic diet and maintaining a physical activity program
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stimulated C-peptide Index during an Oral Glucose Tolerance Test is a measure of Beta Cell Function and will be measuresd at baseline and at 16 weeks after treatment with GLP-1 Receptor Agonist or SGLT2-Inhibitor | Baseline, 16 weeks | Primary Outcome Measure: The stimulated c-peptide index a primary outcome measure and is measured at baseline and 16 weeks. Change in the stimulated c-peptide index is the 16 week value minus the baseline. Higher numbers of the c-peptide index indicate better beta cell function while lower numbers indicated worse beta cell function. The stimulated c-peptide index is a calculated ratio of the c-peptide (ng/ml) to glucose levels (mg/dl) used to assess pancreatic beta cell function. It is calculated as the incremental area under the curve (AUC) of plasma C-peptide divided by the incremental AUC of plasma glucose (∆C-peptide 0-120/∆ Glucose 0-120). The outcome measure of plasma c-peptide (ng/ml) and plasma glucose (mg/dl), during the OGTT (after an overnight fast) at -15, 0, 10, 30, 45, 60, 90 and 120 minutes are combined into one primary outcome variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1 . Title: Change in Glycemic Control Measured at Baseline and 16 Weeks of Treatment with GLP-1 receptor Agonist or SGLT-2 Inhibitors | Baseline, 16 weeks | Description: The outcome measure for glycemic control is hemoglobin A1c (%) measured at baseline and at 16 weeks. Change in hemoglobin A1c is the 16 week value minus the baseline. A negative change in hemoglobin A1c is an improvement in glucose control while a positive change suggests worsening outcomes. |
| Change in Body Weight from Baseline and 16 Weeks of Treatment with GLP-1 receptor Agonist or SGLT-2 inhibitors | Baseline, 16 weeks | The outcome measure of body weight in Kg will be measured at baseline and 16 weeks. Change in body weight is the value at 16 weeks minus the baseline. A negative change in body weight is an improvement in weight while a positive change may suggest worsening body weight |
Countries
United States
Outcome results
None listed