Outcomes of Physiologic Insulin Resensitization (PIR) in Patients With Chronic Kidney Disease and Type 2 Diabetes Mellitus

Is age 18 or older (male or female)

Have a documented diagnosis of CKD stage 3b, 4, or 5 and T2DM of 6 months or greater prior to screening. Patients may have treatment regimens associated with T2DM that include diabetic oral and/or injectable medications including insulin and/or GLP-1 receptor agonists.

In the opinion of the Investigator, has been on an appropriate, stable regimen for management of any complications present for the past six (6) months.

In the opinion of the Investigator, is able to do all of the following:

• Provide valid informed consent.
• Understand and comply with study procedures as presented in the consent process.
• Has the capacity or support to attend all required visits.

If female, the subject must meet either of the following sets of conditions:

o Is of non-childbearing potential, defined as meeting either of the following criteria:

Age ≥50 years and post-menopausal for at least one (1) year

Surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy

Is of childbearing potential and meets both of the following criteria:

• Has a negative serum pregnancy test (beta-human chorionic gonadotropin) at screening.
• Agrees to practice an acceptable method of birth control (contraception) from screening until at least 30 days after last study treatment

Has in the past two (2) years received treatment for a malignancy.

Current pregnancy or intends to become pregnant during the study

Has in the past one (1) year used non-prescription opioids or psychoactive drugs.

Has in the past six (6) months had a hypoglycemic event requiring urgent care and/or administration of glucagon, osteocalcin, or parenteral glucose, unless approved for enrollment by the Medical Monitor.

Has within the past one (1) month participated in a clinical study involving either of the following:

• An investigational drug or procedure for any clinical indication
• An investigation method for glucose control using approved agents

Is nursing or is planning to nurse during the study.

Has at screening a positive test for HIV (4th gen. screen), HBsAg, or HCV viral load.

Has at screening, one or more of the following abnormal lab results:

• Hb <8 g/dL
• WBC <2,000/µL
• Platelets <50,000/µL
• ALT, AST, or Alkaline Phosphatase >5x ULN
• ALT or AST >2.5x ULN, and Total Bilirubin >2x ULN
• Serum albumin <3 g/dL

Has - in the opinion of the Investigator - psychiatric, behavioral, cognitive and/or clinical dysfunction (whether or not related to known medical illness or drug / alcohol use) that would affect the subject's safety and/or compliance.

Is on active dialysis at time of screening