Type 2 Diabetes Mellitus
Conditions
Keywords
Roux-en-y gastric bypass, GLP-1, Liraglutide, OPTIFAST
Brief summary
Type 2 diabetes (DM2) is a chronic disease affecting 29 million Americans and a leading cause of blindness, kidney failure, and limb loss (Engelgau et al 2004). Roux-en-Y gastric bypass (RYGB) is the only intervention that leads to durable DM2 remission \ 80% of the time (Mingrone et al 2012). Yet, it's broad application is limited by cost, invasiveness, and clinical inertia. Medically reproducing RYGB would extend the benefit of disease remission to the vast majority of DM2 patients using a cheaper, less invasive and more palatable treatment approach. Although all of the mechanisms mediating DM2 remission are not known, it is widely accepted that RYGB induces caloric restriction and enhances meal-stimulated release of a gut-peptide called glucagon-like-peptide-1 (GLP-1) both of which improve glycemic control in type 2 diabetes (Dar et al 2012; Jackness 2013). Caloric restriction can be achieved using OPTIFAST which is a commercially available medical weight loss program that has demonstrated the ability to decrease weight and improve glycemic control (Kirschner et al; 1998). Enhanced meal-stimulated GLP-1 release can be achieved using Liraglutide an FDA-approved once daily GLP-1 analogue that improves glycemic control and induces weight loss. The investigators hypothesize that adding OPTIFAST (caloric restriction) in suboptimally controlled DM2 patients on Liraglutide (enhanced meal stimulated GLP-1 release), Metformin and Lantus insulin will medically reproduce RYGB and lead to DM2 remission, weight loss, decreased medication intensity and improved health related quality of life.
Detailed description
This is a 24 week proof of concept study that will examine if adding caloric restriction (OPTIFAST) to enhanced GLP-1 release (Liraglutide) will lead to discontinuation of Lantus and Metformin. The primary outcome measure is change in glycemic control measured as hemoglobin A1C. Secondary outcome measures are change in weight, medication intensity and health related quality of life.
Interventions
OTHEROPTIFAST
OPTIFAST meal replacement includes shakes, bars and soups. These meal replacements will completely replace the subject's diet for the first 12 weeks of the study (baseline-week 12) followed by a gradual transition back to prepared meals over 6 weeks (week 13-18). Attempt will be made to reduce or eliminate Lantus and Metformin as long as glycemic control is maintained.
Sponsors
Société des Produits Nestlé (SPN)
Durham VA Medical Center
East Carolina University
Moahad S Dar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Proof of concept study
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* male or female * age 25-70 years * BMI \> 30 * diagnosis of type 2 diabetes * weight stable for 3 months * hemoglobin A1C \>7% and \<10% * on Liraglutide * on Metformin * on Lantus * interested in losing weight * agreeable to regular visits per study protocol * access to telephone and reliable transportation * has a VAMC provider
Exclusion criteria
* age \>70 * A1C \<7% or \>10% * current use of prandial insulin * current use of sulfonylurea or any other oral agent except for Metformin * current sue of any other basal insulin except for Lantus * pregnant * breast feeding * prior history of pancreatitis * prior history of gastroparesis * history of thyroid cancer/multiple endocrine neoplasia/thyroid nodules/medullary thyroid cancer * history of gallstones * history of hyperoxaluria or calcium oxalate nephrolithiasis * AST/ALT \> 2 times the upper limit of normal * current or past history of liver disease * history of Roux-en-Y gastric bypass or gastric sleeve or any other bariatric procedure * type 1 diabetes * any gastrointestinal disease causing malabsorption * unwilling or unable to complete scheduled testing * thiazolidinedione use within past 6 months * any serious and/or unstable medical, psychiatric, or other condition(s) that prevents the patient from providing informed consent or complying with the study * organ transplantation or those on immunosuppressants * chronic anticoagulation * recent myocardial infarction, unstable angina, stroke, coronary artery bypass or transient ischemia attacks in the past 6 months * chronic prednisone use * peptic ulcer disease in past 6 months * acute gastrointestinal disorders * hepatitis * cirrhosis * GFR \< 50 * deep vein thrombosis in the past 6 months * bone fractures in the past 6 months * lithium use * active malignancy * substance abuse * unstable psychiatric condition * history of suicidal ideation * enrolled in another research study related to diet and/or physical activity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycemic control | Change in HbA1c from baseline at week 12 and week 24 will be measured | Hemoglobin A1C (HbA1C) will be used to assess glycemic control during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight | Change in weight in kilograms from baseline at week 12 and week 24 will be measured | Weight in kilograms will be used to assess weight change during the study |
| Change in Medication intensity | Change in MES from baseline at week 12 and week 24 will be measured | Medication effect score (MES) will be used to assess medication intensity during the study |
| Change in Health Related Quality of Life (HRQOL) | Change in PAID from baseline at week 12, and week 24 will be measured | Problem Areas in Diabetes Scale (PAID) is a well-validated measure used in clinical trials regarding diabetes and is a sensitive and specific measure of HRQOL. |
| Change in Health Related Quality of Life | Change in EQ-5D-5L from baseline at week 12 and week 24 will be measured | EQ-5D-5L is a highly sensitive 5-item health status measure with good performance in Veteran outpatients. It assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. |
| Change in Physical activity | Change in IPAQ from baseline at week 12 and week 24 will be measured | International Physical Activity Questionnaire (IPAQ) is a well validated tool to assess daily physical activity |
Countries
United States
Outcome results
None listed