Primary Care Pragmatic, Real World Experience for Automated Insulin Delivery

Inclusion criteria

• Age at time of consent \>18 and \<89 years
• Either 2.a. or 2.b.:
• Clinical diagnosis of type 1 diabetes for at least one year and using insulin for at least 1 year
• Clinical diagnosis of type 2 diabetes, on current injected or infused insulin regimen for at least 3 months prior to screening (e.g., basal-bolus, basal only, or pre-mix)
• Stable doses of glucose lowering medications over the preceding 4 weeks as determined by Investigator, including GLP-1 receptor agonists (GLP-1 RA) and GLP-1/GIP RA agents
• Stable doses of weight loss medications (including GLP-1 RA and GLP-1/GIP RA agents) over the preceding 4 weeks as determined by the investigator.
• For those using the iLet Bionic Pancreas (during the RCT arm or observational extension phase), willingness to stay on current doses of medications throughout the study that may affect glycemia directly and/or indirectly, except for a dose reduction or discontinuation.
• Have a primary care clinician willing to refer them to the study, confirm their diabetes diagnosis (for example: type 1 diabetes or type 2 diabetes), and recommend and manage the iLet for the duration of the study
• Willing to comply with all study procedures for the duration of the study
• Willing to wear a Dexcom CGM device and iLet system for duration of time randomized to iLet use or OEP
• Willing to use the following insulin: lispro (including non-branded lispro and Humalog) or aspart (including non-branded aspart, Fiasp, and Novolog)
• Investigator has confidence that the participant has the cognitive ability and can successfully operate all study devices and can adhere to the protocol
• Willing and able to sign and date the Informed Consent Form (ICF)
• If capable of becoming pregnant, willing and able to have pregnancy testing and use an acceptable method of contraception during the study period
• a. Capable of becoming pregnant means that menstruation has started and the participant is not surgically sterile or post-menopausal (12 months without menses) b. Acceptable methods of contraception include: i. Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
• ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
• iii. Placement of an intrauterine device or intrauterine hormone-releasing system.
• iv. Barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository).
• v. Has a vasectomized or sterile partner (where partner is sole partner of participant) and where vasectomy has been confirmed by medical assessment.
• vi. Exercises true sexual abstinence. Sexual abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study.
• Agreement to adhere to Lifestyle Considerations (see Section 5.3) throughout study duration
• Have hardware and internet access capable of 2-way video and audio communication

Exclusion criteria

• Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the bionic pancreas, impaired memory)
• Unable to speak and read English, as iLet BP support materials and device menus are currently available in English only
• Diagnosis of maturity-onset diabetes of the young (MODY)
• Plan to change usual diabetes regimen between screening and study randomization
• This would include changing from MDI to pump or from pump to MDI, starting a new class of type 2 diabetes medication, or starting or increasing GLP-1 RA or GLP-1/GIP RA medication
• This would NOT include changes to any insulin doses, including pump settings, short- and/or long-acting insulin doses and type of insulin; changing type 2 diabetes medication dosing (except GLP-1 RA or GLP-1/GIP RA); or changing type of type 2 diabetes medication within the same class
• Weigh more than 255 kg (561 pounds) as this is the maximum weight that can be entered into the iLet user interface
• History of bariatric surgery within 12 months prior to enrollment or plans for bariatric surgery within the period of study participation
• Current use of a closed-loop or hybrid closed-loop insulin delivery system that is not FDA-cleared (e.g. "DIY Loop", "AAPS", "iAPS" or "Open APS")
• Diagnosed blood disorder or dyscrasia associated with hemolysis, including for example: sickle cell disease and thalassemia, which in the Investigator's opinion could interfere with HbA1c accuracy
• Planned use of hydroxyurea at any dose and/or of acetaminophen at doses exceeding 1 gram (1000 mg) every 6 hours.
• Plans to receive a blood transfusion over the course of the study or has received a transfusion within 3 months prior to enrollment
• Current participation in another diabetes-related clinical trial
• History of diabetes due to cystic fibrosis, pancreatitis, or other pancreatic disease, including pancreatic tumor or insulinoma, or history of complete pancreatectomy
• Have a history of intermittent oral or injectable glucocorticoid treatment within 8 weeks prior to screening or plans to take intermittent oral or injectable glucocorticoid during the study (chronic, stable treatment is acceptable, unplanned use is acceptable)
• History of more than 1 episode of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS) in the 6 months prior to screening, unrelated to an intercurrent illness or to a kinked, dislodged, or occluded cannula
• Established history of allergy or severe reaction to adhesive or tape that must be used in the study
• Treated currently or within the past 30 days prior to enrollment, or plan to begin treatment, with sulfonylurea, pramlintide, or SGLT-2 inhibitor medication
• Any planned surgery during the study that would be considered major in the opinion of the investigator
• Pregnant or lactating, or planning to become pregnant in the next 6 months
• Renal failure on dialysis or chronic renal disease with a GFR or eGFR \<30mL/min (values within the last two years will be accepted; if none available or \>2 years prior, participant will be instructed to obtain GFR or eGFR through their usual care provider and to make copy of result available to study team)
• Any condition or circumstance that, in the opinion of the site principal investigator, could interfere with the safe or effective completion of the study or which could compromise the results of the study c. Conditions to be considered by the investigator may include, but are not limited to, the following: i. Active clinical diagnosis of substance use disorder ii. Chronic use of opiates and/or benzodiazepines which, in the opinion of the investigator, might make it difficult for the participant to follow study procedures iii. Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g. exercise of intensity up to 6 METS) 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 iv. Known history of prolonged QTc interval, malignant arrhythmia, or severe congenital heart disease v. Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV vi. History of TIA or stroke in the last 12 months vii. Untreated or inadequately treated mental illness viii. History of untreated or inadequately treated eating disorder within the last 2 years, such as anorexia, bulimia, or diabulimia, or omission of insulin to manipulate weight ix. History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
• Plans to travel outside of the US and its territories for more than four weeks consecutively
• Plans not to have internet/video/phone access for more than one week consecutively
• Employed by, or having immediate family members employed by Beta Bionics, or being directly involved in conducting the clinical trial, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial
• Previous use of the iLet for more than four weeks (including use of the commercially available iLet or prior participation in a study involving wearing the iLet for more than four weeks)