The RESET System Pivotal Clinical Trial (Protocol Revision K)

Prior treatment

• Previous treatment with the RESET System
• Previous GI surgery that could preclude the ability to place the RESET Liner or affect the function of the RESET Liner, or abnormal GI anatomical finding that could preclude the ability to place the RESET Liner or affect the function of the RESET Liner
• Prior history of an abscess requiring hospitalization, intravenous antibiotics or drainage
• Previous treatment for severe liver disease and/or biliary tract disease, including but not limited to, surgery, bile duct dilatation, and stent placement
• Current alcohol addiction, current drug addiction or usage, of drugs such as, narcotics, opiates, or benzodiazepines and other addictive tranquilizers
• Diagnosis of osteopenia or osteoporosis or currently taking denosumab, romosozumab-aqqg, bisphosphonates or teriparatide
• Active or recent (less than 12 months) gastroesophageal reflux disease (GERD), unless treated with H2Ras not PPI.
• Currently taking prescription antithrombotic therapy (e.g. anticoagulant or antiplatelet agent) within 10 days prior to randomization and/or there is a need or expected need to use during the trial 9 months post implant procedure
• Currently taking the following medications (within 30 days prior to randomization) and/or there is a need or expected need to use these medications during the trial 12 months post index procedure: Restricted Medications/Supplements Systemic corticosteroids Proton Pump Inhibitor (PPI) Drugs known to affect GI motility (e.g.metoclopramide) Prescription or over-the-counter weight loss medication(s) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), aspirin, ibuprofen, and other anti-inflammatory medication for study duration Medications known to cause significant weight gain or weight loss (e.g. chemotherapeutics) Supplements that are known or suspected to increase bleeding risk including but not limited to: Gingko biloba Ginseng Vitamins C \& E Turmeric St. John's wort Evening primrose oil Feverfew Green Tea Extract
• Having donated blood or received a blood transfusion in the 90 days prior to baseline labs. Patients should agree not to donate blood during the study

Other illness

• Known history of liver disease (e.g., viral or autoimmune etiology, METAVIR grade 2 or higher fibrosis/cirrhosis from a biopsy within the past 6 months, but not including incidental fatty liver)
• Diagnosis of type 1 diabetes mellitus or having any history of ketoacidosis
• History of pancreatitis, including gallstone related pancreatitis (subsequent to which patient has cholecystectomy)
• Diagnosis of autoimmune connective tissue disorder (e.g. lupus erythematosus, scleroderma)
• Uncontrolled thyroid disease, including a history of thyroid cancer, hyperthyroidism, or taking thyroid hormone for any reason other than primary hypothyroidism (TSH level must be between 0.4-4)
• History of Crohn's disease, atresias or untreated stenoses
• Abnormal pathologies or conditions of the gastrointestinal tract, including ulcers or upper gastrointestinal bleeding conditions within 3 months of randomization
• Patients may be disqualified for study inclusion for any condition determined by the PI that places patient at undue risk.
• History or observation of psychological disorder or behavior which could preclude compliance to the treatment and follow up plan
• Any condition that increases red cell turnover, such as thalassemia
• Existence of (\>5 cm string test) Pseudomonas aeruginosa, Stenotrophomonas maltophilia and/or Klebsiella pneumoniae serotype K1 and K36. A known sensitivity to nickel or titanium
  • 37\. Do not meet the screening criteria for Fibroscan (i.e., Fibroscan unsafe, or Fibroscan conditional but not appropriate for the region of interest 38. History of myocardial infarction, stroke, or hospitalization for heart failure 39. History Afib and/or cardiac arrythmias 40. History of unstable angina 41.History of new or worsening signs or symptoms of CAD within the last 3 months 42.Any contraindication to general anesthesia or high risk for general anesthesia as determined by anesthesiologist (e.g., ASA score 4 or higher)

Lab values

• eGFR of less than 45 ml/min/1.73 m2
• Triglyceride level \> 600 mg/dL
• Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 100,000/microliter, or known coagulopathy

Other

• Hypoglycemia and/or DKA/HHNK in the last 6 months requiring 3rd party assistance.
• Fasting C-peptide \< 1.0 ng/mL
• Vitamin D deficiency (\<20ng/ml)
• Height \< 5 feet (152.4 cm)
• Active H. pylori
• Poor dentition not allowing complete chewing of food
• Enrolled in another investigational study within 3 months of screening for this study (enrollment in observational studies is permitted)
• Residing in a location without ready access to study site medical resources
• Documented weight loss of 5% total body weight (TBW) anytime during the 3 months preceding randomization
• Positive Fecal Immunochemical Test (FIT)
• No access to an active telephone and internet service for provision of Follow Up Schedule calls and electronic diary

• Age ≥22 years and ≤ 65 years
• Have understood and signed the approved informed consent form
• Diagnosis of type 2 diabetes
• HbA1c ≥ 7.5% and ≤10%
• BMI ≥30kg/m2 and ≤ 50kg/m2
• Willing and able to comply with study requirements
• Documented negative pregnancy test in women of childbearing potential
• Women of childbearing potential not intending to become pregnant (continue to be on an approved form of birth control) for the duration of their trial participation, including post explant period. Women of child-bearing age without known sterilization will be placed on 1 form of birth-control to prevent unwanted pregnancies
• At least one year of medical records available, including detailed medical therapy and dosing information
• Failed to achieve adequate HbA1c reduction (\<7.5%) after dual therapy for at least 3-month stable dosage of diabetes medication(s), including insulin, metformin, SGLT-2 inhibitor, GLP-1 RA, Dual GLP-1/GIPR agonist or, other medications including meglitinides, sulfonylureas, thiazolidinediones, or DPP-4s.