GPR119 Agonist for Hypoglycemia in Type 1 Diabetes

INCLUSION CRITERIA

Type 1 diabetes cohort:

• Age 20-60 years
• Diagnosis of T1DM according to American Diabetes Association (ADA) criteria continuously requiring insulin for survival
• Diabetes diagnosis performed more than 5 years before enrollment
• Fasting C-peptide levels 90 mg/dL (Labs may need to be repeated if the Plasma glucose is 6 months post-partum and not lactating and agrees not to become pregnant during the study and for at least 2 weeks after the last dose of the study medication. For male participants: agrees not to donate sperm or not to get a woman pregnant during the study and for at least 2 weeks after the last dose of the study medication.

Healthy subject cohort:

• Age 20-60 years
• General good health
• Creatinine clearance >80 mL/min based on CKD-EPI equation
• Fasting blood glucose (FBG) >70 mg/dL and 6 months post-partum and not lactating and agrees not to become pregnant during the study

EXCLUSION CRITERIA

• BMI >35 kg/m2 and 35 kg/m2 and 2.5 times the upper limit of normal)
• Kidney disease (creatinine >1.6 mg/dl or estimated GFR 500 mg/dl, LDL >200 mg/dl or unstable hyperlipidemia. Treatment with a single lipid lowering agents is allowed if stable within the previous 3 months.
• Anemia (hemoglobin 10 µIU/ml if asymptomatic)
• Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic) or treatment with more than 2 antihypertensive medications.
• Current use of beta-adrenergic blocking agents or their use was stopped less than one month before recruitment
• History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable)
• History of organ transplant
• History of HIV, active Hepatitis B or C, or Tuberculosis
• Pregnancy, lactation or 6 months postpartum from the scheduled date of screening lab collection
• Females of childbearing potential (any female except those with tubal ligation, hysterectomy, or absence of menses >2 years) unwilling to use an approved method of contraception (one medically accepted method of contraception with ≥99% effectiveness when used consistently and correctly). Male participants: he or he and his partner unwilling to use an approved method of contraception with ≥99% effectiveness when used consistently and correctly
• History of Major Depression in the last 5 years
• History of an eating disorder
• History of bariatric surgery
• History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years
• Self-report of marijuana use ≥3 days/week in any form
• Psychiatric disease prohibiting adherence to study protocol
• Current use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs
• Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone or estrogen replacement therapy). Hormone based contraception is acceptable.
• Use of any medications known to influence glucose, fat and/or energy metabolism (e.g., growth hormone therapy, glucocorticoids [steroids], prescribed medications for weight loss, etc.). Patients on medications with acute effects on glucose metabolism used for other indications (certain antidepressants, ADHD and antiepileptic medications) may be enrolled if they have been on chronic, stable doses (≥6 months)
• Uncontrolled seizure disorder
• Current night shift worker
• Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete study visits
• Unwilling and/or unable to follow and comply with scheduled visits and protocol requirements

Additional exclusion Criteria for the type 1 diabetes cohort:

• HbA1c >9%
• Insulin dose less than 0.3 U/kg or low carbohydrate diet
• History of T2DM or any form of diabetes other than T1DM
• Hypoglycemia unawareness as assessed using the GOL