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

Phase 4

Withdrawn

Interventions: Drug: Exenatide-LAR plus Dapagliflozin placebo
Drug: Exenatide-LAR plus Dapagliflozin
Drug: Insulin Titration
Behavioral: Behavioral Therapy

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

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

Arm && Interventions

Group	Intervention	Description
Group 2	Exenatide-LAR plus Dapagliflozin placebo	Exenatide-LAR plus Dapagliflozin placebo, basal insulin titration, and behavioral therapy.
Group 2	Insulin Titration	Exenatide-LAR plus Dapagliflozin placebo, basal insulin titration, and behavioral therapy.
Group 2	Behavioral Therapy	Exenatide-LAR plus Dapagliflozin placebo, basal insulin titration, and behavioral therapy.
Group 1	Insulin Titration	Insulin titration and behavioral therapy.
Group 1	Behavioral Therapy	Insulin titration and behavioral therapy.
Group 3	Exenatide-LAR plus Dapagliflozin	Exenatide-LAR plus Dapagliflozin, basal insulin titration, and behavioral therapy.
Group 3	Insulin Titration	Exenatide-LAR plus Dapagliflozin, basal insulin titration, and behavioral therapy.
Group 3	Behavioral Therapy	Exenatide-LAR plus Dapagliflozin, basal insulin titration, and behavioral therapy.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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 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

Locations (1): Comprehensive Weight Control Center
🇺🇸
New York, New York, United States