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

Weill Cornell Medicine (WCM)

Status and phase: Withdrawn; Phase 4

Conditions: Diabetes Mellitus, Type 2

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02811484

1512016843

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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0 participants in 3 patient groups, including a placebo group

Group 1

Other group

Description:

Insulin titration and behavioral therapy.

Treatment:

Drug: Insulin Titration

Behavioral: Behavioral Therapy

Group 2

Placebo Comparator group

Description:

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

Treatment:

Drug: Insulin Titration

Behavioral: Behavioral Therapy

Drug: Exenatide-LAR plus Dapagliflozin placebo

Group 3

Experimental group

Description:

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

Treatment:

Drug: Insulin Titration

Behavioral: Behavioral Therapy

Drug: Exenatide-LAR plus Dapagliflozin