Roux-en-Y (RYGB) gastric bypass reduces the size and capacity of the stomach and bypasses a portion of the small intestine which leads to decreased food intake and higher levels of a gut hormone called GLP-1 (glucagon-like-peptide-1). These changes lead to weight loss, improved blood sugars and often remission of type 2 diabetes but most patients do not qualify or want surgery. The investigators are searching for ways to make the beneficial effects of RYGB available to most type 2 diabetes patients rather than a select few that undergo RYGB.

The investigators believe that parts of RYGB can be medically reproduced through a combination of diet and medicine. Once weekly injectable GLP-1 medicine that leads to weight loss and improved blood sugar control in type 2 diabetes are now FDA approved. Optifast is a medically supervised diet that safely reduces calorie intake to 800 calories per day for three months by replacing normal meals with specially prepared bars and shakes which leads to weight loss and improved blood sugar control in type 2 diabetes. Normal meals are then gradually reintroduced over 6 weeks and the bars/shakes are stopped. The investigators hypothesize that Optifast (diet) + once weekly GLP-1 will lead to weight loss and improvement in blood sugar control in type 2 diabetes similar to what is seen after RYGB.

MRB II is a two arm 50-week study that will recruit Veteran DM2 patients already on a stable dose of a GLP-1 agonist +/- DM2 agents. The investigators will recruit 50 patients and assign 25 subjects to the control arm and 25 subjects to the experimental arm. The control and experimental arm (n=25) will have in-person visits with the study PI, certified diabetes educator (CDE) and behavioral psychologist (Psych) at baseline, week 12, week 24 and week 48 to optimize glycemic control. Visits with the PI will be one-on-one but visits with CDE/Psych will be shared-medical appointments. Furthermore, the experimental arm (n=25) will also be enrolled in the Optifast medical weight loss program starting with a 2-week run-in phase to determine if they are able to tolerate Isocaloric Optifast (7 meal replacements/day) while also minimizing significant weight loss prior to the start of the study. The patients in the experimental arm successfully completing the run-in phase will then continue and enter the 50-week study.

Inclusion Criteria:

• male or female
• age 25-75 years
• BMI >27
• diagnosis of type 2 diabetes
• weight stable for 1 month
• hemoglobin A1C >7.0%
• on stable dose of once weekly GLP-1 agonist
• on oral or injectable DM2 medicines
• interested in losing weight
• agreeable to regular visits per study protocol
• access to telephone and reliable transportation and has a VAMC provider
• using a Freestyle Libre glucose monitoring device and/or glucometer device

Exclusion Criteria:

• age >75,
• A1C <7%
• pregnant
• breast feeding
• prior history of pancreatitis
• prior history of gastroparesis
• history of thyroid cancer/multiple endocrine neoplasia/thyroid nodules/medullary thyroid cancer (contraindication to Liraglutide)
• history of gallstones
• history of hyperoxaluria or calcium oxalate nephrolithiasis
• history of Roux-en-Y gastric bypass or gastric sleeve or any other bariatric procedure,
• type 1 diabetes
• any abnormality on the screening EKG that could subject patient to increased risk during the study
• any gastrointestinal condition causing malabsorption (including but not limited to inflammatory bowel disease, celiac sprue)
• unwilling or unable to complete scheduled testing
• 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
• hepatitis
• cirrhosis
• GFR <50
• deep vein thrombosis in past 6 months
• active malignancy
• unstable psychiatric condition including active or current suicidal ideation
• enrolled in another research study related to diet and/or physical activity

Data and/or specimens will be transported BETWEEN sites that are under the auspices of the Durham VA Medical Center. The Greenville VA Health Care Center is the primary study site. Data analysis will be conducted by HSRD located at the Durham VA medical center. Data and/or specimens will be transported to non-VA/VHA sites (e.g., academic affiliates, laboratories, etc.) as coded data which will be shared via email using Azure RMS encryption. The study will use a VA issued laptop. Direct identifiers will be maintained separately from data and or specimens by using a code to "identify" subjects. In a separate database (i.e., a "linking" or "cross-walk" database) this code will be linked to identifying subject information. Reporting of results, such as in scientific papers and presentations, will never identify individual subjects. Data will be presented in aggregate and individual-level data will not be published. No future use of data is currently planned.

Study protocol was shared with study sponsor prior to IRB submission. Study sponsor will receive a summary of study results at study conclusion but will not have access to individually identifiable information.