Clinical trial NCT02811484: Efficacy of Exenatide-LAR and Dapagliflozin in Overweight/Obese, Insulin Treated Patients With Type 2 Diabetes
Official title: Efficacy of Exenatide-LAR Alone and in Combination With Dapagliflozin in Overweight/Obese, Insulin Treated Patients With Uncontrolled Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Obesity
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2016-06-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change in HbA1c
timeFrame: baseline, 24 weeks
Secondary outcomes:
measure: Change in Body Weight
timeFrame: baseline, 24 weeks
measure: Change in waist circumference
timeFrame: baseline, 24 weeks
measure: Change in fasting glucose
timeFrame: baseline, 24 weeks
measure: Change in fasting lipids
timeFrame: baseline, 24 weeks
measure: Change in blood pressure
timeFrame: baseline, 24 weeks
measure: Change in total dose insulin
timeFrame: baseline, 24 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Comprehensive Weight Control Center
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Alpana P Shukla, MD
role: PRINCIPAL_INVESTIGATOR
References: