Beta Cell Function in Type 2 Diabetes in Black Patients: Differential Effects of SGLT2 Inhibitors and GLIP-Receptor Agonists
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 24 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Agrees to participate (signs and dates the informed consent) and agrees to all study procedures and conditions of the protocol.
- •Black (self-identified) patients with relatively recent onset (< 15 years) DM2
- •aged >= 24 years of age (adults < age 24 years old need additional resources to consistently participate, and may have different metabolism)
- •HbA1c between 6.9% and 10%, inclusive
- •BMI > 23 and < 45 kg/m2, and stable body weight over 2 months
- •In good general health, as evidenced by medical history and physical examination. And not having any of the specific items of the
排除标准
- •Currently taking no diabetes medication or on stable doses (2 months) of metformin or metformin plus sulfonylureas without additional diabetes medication(s).
- •Ability to take and agree to taking oral medication and to self-inject
- •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.
- •Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout the study, including following a diabetic diet and maintaining a physical activity program
- •Exclusion Criteria:
- •Poor general health, low kidney function (eGFR < 45), abnormal liver blood tests (AST and ALT > 3 times the ULN, Bilirubin 2 x ULN), serious cardiovascular, liver or renal disease, known proliferative retinopathy, type 1 diabetes, pancreatitis or pancreas cancer, medullary thyroid cancer, MEN2 (or family history of MEN2), current low hematocrit (< 35% for men and 33% for women, frailty, at risk for falls, current (past six months) alcohol or substance use disorder, history of a non-traumatic bone fracture, amputation, organ transplant, HIV or COVID, or if the patient cannot complete study activities.
- •Current regular use of DDP-4 inhibitors, insulin or GLP-1 RA or SGLT2-inhibitors
- •Currently pregnant, planned pregnancy in the next 7 months or nursing/lactating.
- •Known allergic reactions to either the study medication
- •Treatment with another investigational drug or other intervention within 4 months, or plan to enroll in another interventional study during their participation in this study
- •Planned major surgery
- •Recent (within 6 months): MI, Stroke, Cerebrovascular accident or unstable angina or revascularization procedures, grade 3 or 4 heart failure
- •Use of weight loss medication, weight loss surgery.
- •Use of glucocorticoids for chronic illness within 8 weeks prior to screening or likely to begin glucocorticoids during study period
- •Study doctor considers subject a poor study candidate
- •Cancer - History of active or untreated malignancy or in remission from a clinically significant malignancy for < 5 years; exception: basal cell carcinoma of the skin.
研究组 & 干预措施
GLP1-RA
We will examine the effect of GLP-1 RA on pancreatic beta cell function as measured by insulin, C-peptide and glucose serum concentrations during OGTT.
干预措施: GLP1-RA (Drug)
SGLT-2i
We will examine the effect of SGLT-2i on pancreatic beta cell function as measured by insulin, C-peptide and glucose serum concentrations during OGTT
干预措施: SGLT-2 inhibitor (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
- 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)
- Change in Body Weight from Baseline and 16 Weeks of Treatment with GLP-1 receptor Agonist or SGLT-2 inhibitors(Baseline, 16 weeks)
研究者
MaryAnn Banerji
Professor of Medicine, Endocrinologist
State University of New York - Downstate Medical Center