Safety and Efficacy of the Fully Closed Loop iLet Bionic Pancreas in Adults with Type 1 and Type 2 Diabetes

Inclusion Criteria 
1.    Age ≥18 years at time of screening 
2.    Diagnosed with type 1 diabetes or with type 2 diabetes and using insulin for at least 90 days at the time of enrollment 
3.    Stable insulin regimen type in the last 90 days prior to enrollment 
a.    Any changes to the overall regimen (i.e., going from basal only to a basal-bolus regimen, going from multiple daily injections (MDI) to a pump, etc.) in the last 90 days will be exclusionary, but dose adjustments (i.e., increasing the basal dose, changing pump settings, etc.) are not considered changes to the regimen for this purpose 
4.    Stable insulin doses for the last 30 days prior to enrollment 
a.    Any adjustments to insulin doses or pump settings implemented in the last 30 days prior to enrollment will be considered exclusionary
5.    Willing to use only compatible rapid-acting or ultra rapid-acting insulin in the iLet for the duration of the study 
6.    Stable regimen of non-insulin glucose lowering medications over the preceding 90 days prior to enrollment 
a.    Any changes to class of drug used (i.e., changing from GLP-1 receptor agonist to an SGLT2 inhibitor, starting a new GLP-1 receptor agonist, etc.) in the last 90 days will be exclusionary, but changes between drugs of the same class (i.e., changing from dulaglutide to semaglutide, etc.) are not considered changes to the regimen
b.    Type 1 diabetes population only: use of metformin and GLP-1 receptor agonists will be allowed, provided other inclusion criteria are met. Use of any other non-insulin glucose lowering medications (including SGLT2 inhibitors) in the 90 days prior to enrollment will be considered exclusionary.
7.    Stable doses of non-insulin glucose lowering medications over the last 30 days prior to enrollment
a.    Any adjustments to doses of non-insulin glucose lowering medications implemented in the 30 days prior to enrollment will be considered exclusionary
8.    Willing to not change doses from baseline non-insulin glucose lowering medications during the trial unless required for safety or tolerability purposes 
9.    Willing to not initiate use of any new non-insulin glucose-lowering during the trial 
10.    Stable CGM use over the last 90 days prior to enrollment
a.    Starting CGM use for the first time during the 90 days prior to enrollment is considered exclusionary. 
b.    Intermittent use of a CGM (e.g., for insurance reasons, take breaks, etc.) over the last 90 days is not exclusionary as long as this is consistent with their usual pattern of CGM use
c.    Regardless of previous CGM use, no CGM use during the last 90 days prior to enrollment is not exclusionary – these individuals should be considered CGM non-users
11.    Able to read and understand English  

Exclusion Criteria 
12.    Unable to provide informed consent (e.g., impaired cognition or judgement) 
13.    Unable to safely comply with study procedures and reporting requirements (e.g., impairment of vision or dexterity that prevents safe operation of the FCL iLet, impaired memory) 
14.    a. For people with type 1 diabetes: Current use of any non-insulin glucose lowering medications other than metformin or GLP-1 receptor agonists (past use with discontinuation more than 90 days prior to enrollment is acceptable)
b. For people with type 2 diabetes: Current use of sulfonylurea or meglitinide medications (past use with discontinuation more than 90 days prior to enrollment is acceptable) 
15.    Use of medication or supplements that are known to interfere with CGM sensor accuracy and, in the opinion of the treating physician, cannot be discontinued during the study period
a.    If a participant requires such medication, they must use an alternative compatible CGM sensor that is not affected by that medication for the duration of the baseline CGM data collection and 13-week FCL iLet study period.  
b.    Medications known to interfere with CGM accuracy include but are not limited to: 
i.    Hydroxyurea (any dose) – interferes with Dexcom CGMs 
ii.    Ascorbic acid (vitamin C) >1000 mg/day – interferes with Abbott FreeStyle Libre 3 Plus (> 500 mg/day interferes with Abbott FreeStyle Libre 3)
iii.    Aspirin (acetylsalicylic acid) or salicylic acid >650 mg/day – interferes with Abbott FreeStyle Libre 3 Plus 
16.    Known hemoglobinopathy or condition/medication use that would interfere with accurate determination of HbA1c, in the investigator's opinion (e.g., hemolytic anemia, sickle cell disease, recent transfusion); sickle cell trait is not an exclusion 
17.    History of cystic fibrosis, diabetes secondary to pancreatitis, or other pancreatic diseases, including pancreatic tumor or insulinoma, or history of complete pancreatectomy 
a.    Pancreatitis following a diagnosis of diabetes is not exclusionary
18.    Tape allergy or skin condition that will preclude use of the study pump or CGM 
19.    Pregnant (positive urine human chorionic gonadotropin (hCG)) or lactating, planning to become pregnant during the study, or sexually active without the use of appropriate contraception 
a.    Acceptable methods of birth control by participants of child-bearing potential for use in this study include hormonal birth control, such as birth control pills, vaginal ring, skin patch, injection, implant, or hormonal intrauterine system (IUD); a non-hormonal intrauterine device, such as a copper IUD; tubal ligation; or barrier methods such as condoms.
b.    Participants who are not capable of becoming pregnant are not required to use contraception for the purposes of study participation. For clarity, this includes male participants who do not have the biological capacity to become pregnant. The contraception requirement addresses pregnancy-specific maternal and fetal risks, including those associated with diabetes during pregnancy. No male-mediated reproductive or fetal risk has been identified; therefore, contraception in this population would not provide an additional study-related safety benefit. 
20.    Most recent (within the last 2 years) estimated glomerular filtration rate (eGFR) a.    If no eGFR (or creatinine measurement from which an eGFR can be calculated) is available in the last 2 years, one must be obtained to confirm eligibility 
21.    Current participation in another diabetes-related interventional clinical trial 
22.    Presence of a medical condition or use of a medication that, in the judgment of the site investigator, principal investigator (PI), or medical monitor, could compromise the results of the study or the safety of the participant. Conditions to be considered by the investigator may include: 
a.    Alcohol or drug abuse 
b.    Use of prescription drugs that may dull the sensorium, reduce sensitivity to symptoms of hypoglycemia, or hinder decision making during the period of participation in the study 
c.    Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g. climbing a flight of stairs) despite medical management, or within the last 12 months before screening a history of myocardial infarction, percutaneous coronary intervention, enzymatic lysis of a presumed coronary occlusion, or coronary artery bypass grafting 
d.    Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV 
e.    Untreated or inadequately treated mental illness  
f.    History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight  
g.    History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment 
23.    Unable to follow clinical protocol for the duration of the study or is otherwise deemed unacceptable to participate in the study per the investigator’s clinical judgment. The investigator will take into account the participant’s compliance with current diabetes management and prior acute diabetic complications 
24.    Participant is an employee of Beta Bionics, an Investigator or Investigator’s study team, or immediate family member (spouse, biological or legal guardian, child, sibling, parent) of any of the aforementioned