Diabetes Mellitus, Type 2
Conditions
Keywords
Obesity
Brief summary
The purpose of this study is to see what the effects of using one or two additional diabetes drugs (dapagliflozin and exenatide-LAR) are on blood sugar levels in patients who are taking insulin. This research study is being done to investigate which of these commonly-used medications, medication combinations or increasing insulin dose is better.
Detailed description
This is a single center prospective, randomized, placebo-controlled trial in overweight/obese patients with insulin treated uncontrolled type 2 diabetes Eligible subjects willing to participate in the study will be randomized to one of 3 treatment groups: Group 1: Insulin titration + behavioral therapy Basal insulin titration upto 12 weeks with 2 U increment every 3 days (Fasting glucose goal \<110) based on self-monitored blood glucose. After 12 weeks, patients with HbA1c \>8% will switch to a basal bolus regimen. Group 2: Exenatide-LAR 2mg q week x 24 weeks + Dapagliflozin placebo x 52 weeks + titrated basal insulin +behavioral therapy. Group 3: Exenatide-LAR 2mg q week x 24 weeks plus Dapagliflozin 5mg QD x 2 weeks followed by 10mg QD x22 weeks +titrated basal insulin + behavioral therapy. Behavioral therapy will be delivered by registered dietitians and will include the BMIQ program -a web based medical weight loss program.
Interventions
DRUGExenatide-LAR plus Dapagliflozin placebo
Exenatide-LAR 2 mg every week x 24 weeks plus Dapagliflozin placebo x 52 weeks and behavioral therapy.
DRUGExenatide-LAR plus Dapagliflozin
Exenatide-LAR 2 mg every week x 24 weeks plus Dapagliflozin 5 mg x 2 weeks, then 10 mg for 22 weeks and behavioral therapy.
DRUGInsulin Titration
Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c\>8%
BEHAVIORALBehavioral Therapy
Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Type 2 diabetes * BMI ≥27kg/m\^2 * Hemoglobin A1C 8-12% * English speaking * provided written consent * on a stable dose of metformin and/or glitazone and/or alpha-glucosidase inhibitors for ≥ to 8 weeks
Exclusion criteria
* History of type 1 diabetes * fasting c-peptide \<.8 ng/ml * eGFR \<60 ml/min/1.73 m\^2 * urine albumin-to-creatinine ratio greater or equal to 300 mg/g * AST/ALT greater or equal to 2.5 upper limits of normal * history of infectious liver disease (HBV, HCV) * creatine kinase greater or equal to 3 times the upper limits of normal * unstable or serious cardiovascular, renal, or hepatic disease * symptoms of severely uncontrolled diabetes * history of more than 1 episode of severe/major hypoglycemia within 6 months, active/history of bladder cancer * female patients who are pregnant or intending to become pregnant * women who are breastfeeding * personal/family history of medullary thyroid cancer or MEN2 * fasting triglyceride levels \> 500 mg/dl * history of confirmed pancreatitis * known hypersensitivity or allergy to exenatide or dapagliflozin * are currently enrolled in or discontinued within last 30 days from another study * have any other condition that precludes the patient from following and completing the protocol * history of diabetic ketoacidosis * anti-diabetes medication other than those listed in the inclusion criteria within 8 weeks of screening * history of previous bariatric surgery or planned bariatric surgery during the course of the study * clinically significant abnormal free T4/TSH requiring initiation or adjustment of thyroid treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | baseline, 24 weeks | To determine the efficacy of Exenatide-LAR and Exenatide-LAR plus dapagliflozin in lowering HbA1c compared with insulin titration in obese, insulin treated subjects with uncontrolled Type 2 Diabetes Mellitus at 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in waist circumference | baseline, 24 weeks | To determine the effect of Exenatide-LAR and Exenatide-LAR plus dapagliflozin vs insulin titration on waist circumference in obese, insulin treated subjects with uncontrolled T2DM |
| Change in fasting glucose | baseline, 24 weeks | To determine the effect of Exenatide-LAR and Exenatide-LAR plus dapagliflozin vs insulin titration on fasting glucose (FG) in obese, insulin treated subjects with uncontrolled T2DM |
| Change in Body Weight | baseline, 24 weeks | To determine the effect of Exenatide-LAR and Exenatide-LAR plus dapagliflozin vs insulin titration on body weight in obese, insulin treated subjects with uncontrolled T2DM |
| Change in blood pressure | baseline, 24 weeks | To determine the effect of Exenatide-LAR and Exenatide-LAR plus dapagliflozin vs insulin titration on blood pressure in obese, insulin treated subjects with uncontrolled T2DM |
| Change in total dose insulin | baseline, 24 weeks | To determine the effect of Exenatide-LAR and Exenatide-LAR plus dapagliflozin vs insulin titration on total dose insulin in obese, insulin treated subjects with uncontrolled T2DM |
| Change in fasting lipids | baseline, 24 weeks | To determine the effect of Exenatide-LAR and Exenatide-LAR plus dapagliflozin vs insulin titration on fasting lipids in obese, insulin treated subjects with uncontrolled T2DM |
Countries
United States
Outcome results
None listed