Dexlar: Efficacy of Exenatide-LAR and Dapagliflozin in Overweight/Obese, Insulin Treated Patients With Type 2 Diabetes

Sponsor

Weill Medical College of Cornell University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02811484

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Exenatide-LAR plus Dapagliflozin placebo Drug: Exenatide-LAR plus Dapagliflozin Drug: Insulin Titration Behavioral: Behavioral Therapy	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Efficacy of Exenatide-LAR Alone and in Combination With Dapagliflozin in Overweight/Obese, Insulin Treated Patients With Uncontrolled Type 2 Diabetes

Study Start Date :

Jun 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Group 1 Insulin titration and behavioral therapy.	Drug: Insulin Titration Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c>8% Other Names: Lantus, Levemir, Novolog, Lispro Behavioral: Behavioral Therapy Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.
Placebo Comparator: Group 2 Exenatide-LAR plus Dapagliflozin placebo, basal insulin titration, and behavioral therapy.	Drug: Exenatide-LAR plus Dapagliflozin placebo Exenatide-LAR 2 mg every week x 24 weeks plus Dapagliflozin placebo x 52 weeks and behavioral therapy. Other Names: Bydureon Farxiga Drug: Insulin Titration Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c>8% Other Names: Lantus, Levemir, Novolog, Lispro Behavioral: Behavioral Therapy Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.
Experimental: Group 3 Exenatide-LAR plus Dapagliflozin, basal insulin titration, and behavioral therapy.	Drug: Exenatide-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. Other Names: Bydureon Farxiga Drug: Insulin Titration Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c>8% Other Names: Lantus, Levemir, Novolog, Lispro Behavioral: Behavioral Therapy Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.

Arm

Intervention/Treatment

Other: Group 1

Insulin titration and behavioral therapy.

Drug: Insulin Titration

Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c>8%

Other Names:

Lantus, Levemir, Novolog, Lispro

Behavioral: Behavioral Therapy

Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.

Placebo Comparator: Group 2

Exenatide-LAR plus Dapagliflozin placebo, basal insulin titration, and behavioral therapy.

Drug: Exenatide-LAR plus Dapagliflozin placebo

Exenatide-LAR 2 mg every week x 24 weeks plus Dapagliflozin placebo x 52 weeks and behavioral therapy.

Other Names:

Bydureon

Farxiga

Drug: Insulin Titration

Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c>8%

Other Names:

Lantus, Levemir, Novolog, Lispro

Behavioral: Behavioral Therapy

Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.

Experimental: Group 3

Exenatide-LAR plus Dapagliflozin, basal insulin titration, and behavioral therapy.

Drug: Exenatide-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.

Other Names:

Bydureon

Farxiga

Drug: Insulin Titration

Basal insulin titration up to 12 weeks followed by basal-bolus regimen in those with HbA1c>8%

Other Names:

Lantus, Levemir, Novolog, Lispro

Behavioral: Behavioral Therapy

Subjects will be seen by a registered dietitian and receive nutritional and lifestyle counseling according to a web-based weight management program.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 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 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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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