Please select the eligibility criteria that correspond to the clinical trial below.
Title: Restoring Insulin Secretion Adult Medication Study
Brief Summary: The RISE Adult Medication Study is a 4-arm, 3-center, clinical trial of adults with prediabetes and early type 2 diabetes to address the hypothesis that aggressive glucose lowering will lead to recovery of beta-cell function that will be sustained after withdrawal of treatment. Adult participants (ages 20-65) will be randomized to one of the following treatment regimens: (1) blinded placebo, (2) blinded metformin alone, (3) early intensive insulin treatment with basal insulin glargine followed by open-label metformin, (4) the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide plus open-label metformin.

The primary clinical question RISE will address is: Are improvements in ß-cell function following 12 months of active treatment maintained for 3 months following the withdrawal of therapy? Secondary outcomes will assess durability of glucose tolerance following withdrawal of therapy, and whether biomarkers obtained in the fasting state predict parameters of ß-cell function, insulin sensitivity and glucose tolerance and the response to an intervention.


Options:
A: Inclusion Criteria:

1. Fasting plasma glucose 95-125 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1c ≤7.0%. There is no upper limit for the 2-hour glucose on OGTT.
2. Age 20-65 years
3. Body mass index (BMI) ≥25 kg/m2 but ≤50 kg/m2
4. Self-reported diabetes \<1 year in duration
5. Drug naïve (no prior to oral glucose lowering agent(s), insulin or other injectable glucose lowering agents)

Exclusion Criteria:

1. Underlying disease likely to limit life span and/or increase risk of intervention or an underlying condition that is likely to limit ability to participate in outcomes assessment
2. An underlying disease that affects glucose metabolism other than type 2 diabetes
3. Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
4. Active infections
5. Renal disease (serum creatinine \>1.4 mg/dl for men; \>1.3 mg/dl for women) or serum potassium abnormality (\<3.4 or \>5.5 mmol/l)
6. Anemia (hemoglobin \<11 g/dl in women, \<12 g/dl in men) or known coagulopathy
7. Cardiovascular disease, including uncontrolled hypertension. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
8. History of conditions that may be precipitated or exacerbated by a study drug:

   1. Pancreatitis
   2. Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
   3. Excessive alcohol intake
   4. Suboptimally treated thyroid disease
   5. Medullary carcinoma of the thyroid or MEN-2 (in participant or a family history)
   6. Hypertriglyceridemia (\>400 mg/dl despite treatment)
9. Conditions or behaviors likely to affect the conduct of the RISE Study

   1. Unable or unwilling to give informed consent
   2. Unable to adequately communicate with clinic staff
   3. Another household member is a participant or staff member in RISE
   4. Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
   5. Weight loss of \>5% in past three months for any reason other than post-partum weight loss. Participants taking weight loss drugs or using preparations taken for intended weight loss are excluded.
   6. Likely to move away from participating clinics in next two years
   7. Women of childbearing potential who are unwilling to use adequate contraception
   8. Current (or anticipated) pregnancy and lactation.
   9. Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
10. Additional conditions may serve as criteria for exclusion at the discretion of the local site.
B: Inclusion Criteria:

* Blood glucose criteria must be met
* Not currently on drug therapy for type 2 diabetes
* Body mass index (BMI) in the range 22-45

Exclusion Criteria:

* Pregnancy or lactation
* Type 1 diabetes
* Evidence of serious diabetic complications
* Evidence of serious cardiovascular conditions
* Laboratory value abnormalities as defined by the protocol
* Other protocol-defined exclusion criteria may apply
C: Inclusion Criteria:

* Type 2 Diabetes not well controlled on 1, 2, or 3 oral antidiabetic medications (at least one of them must be metformin and/or a sulfonylurea)

  1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication
  2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications
* Accept treatment with metformin and glimepiride throughout the study, as per protocol
* Willing to inject subcutaneous medication once weekly for LY2189265 or once daily for Insulin Glargine.
* Stable weight for 3 months prior to screening
* Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2)
* Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug

Exclusion Criteria:

* Type 1 Diabetes
* HbA1c equal to or less than 6.5 at randomization
* Chronic insulin use
* Taking drugs to promote weight loss by prescription or over the counter
* Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled
* History of Heart Failure New York Heart Classification III or IV, or acute myocardial infarction, or stroke within 2 months of screening
* Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility
* Hepatitis or liver disease or ALT (alanine transaminase) greater than 3.0 of upper normal limit
* Acute or chronic pancreatitis of any form
* Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatinine clearance of less than 60 milliliters per minute (ml/min)
* History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer
* A serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/ml) at screening
* Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis
* History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years
* Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing
* Organ transplant except cornea
* Have enrolled in another clinical trial within the last 30 days
* Have previously signed an informed consent or participated in a LY2189265 study
* Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening
D: Inclusion Criteria:

* Newly Diagnosed Type 2 Diabetes Mellitus patients not receiving any medication for diabetes
* HbA1c ranging from 7.0% to ≤ 8.5%
* Body Mass Index (BMI) ≥ 19.0 to ≤ 25.0 kg/m2
* Male and female subjects of age between 20 - 60 years shall be selected
* Adult subjects willing to give informed consent
* Subject must be available for and willing to attend all evaluation visits
* Willingness to follow the protocol requirements as evidenced by written informed consent
* Subject must have access to telephone for calling into the clinical center as part of test product compliance

Exclusion Criteria:

* Type 1 diabetes
* BMI ≤18.99 kg/m2 or\> 25 kg/m2
* Presence of severe vascular complications
* Indications for use of insulin
* Elevated serum levels of lipase and amylase (\>1.5 ULN)
* Gamma-glutamyltransferase \>2 times upper limit of normal (ULN) at Visit1, confirmed by repeated measure within 3 working days
* Urine albumin: creatinine ratio (UACR) \>1800 mg/g (\>203.4 mg/mmol)
* Subjects below the age of 20 years and above the age of 60 years
* History of any drug abuse in the past 12 months
* History of hypersensitivity to study drugs and related drugs or excipients in the formulation.
* History of allergy to vegetables and or food substances and or any other manifestations suggestive of hypersensitivity reactions
* Subject who is not willing to participate in the study
* Clinically significant abnormal laboratory results at screening.
* Subject is being treated for severe active infection of any type
* A female subject who is breast-feeding, pregnant, or intends to become pregnant during the study
* Subject with clinically relevant uncontrolled medical condition (e.g hematologic renal hepatic neurology cardiac or respiratory)
* Subject has evidence of active malignancy, or prior history of active malignancy that has not been in remission for at least 5 years
* Participating in a clinical research trial within 30 days prior to screening
* Donated blood 3 months prior to first study visit and during the study period
* Individuals who are cognitively impaired and or who are unable to give informed consent
* Known HIV or Hepatitis B or C positive
* Any other health or mental condition that in the Investigator's opinion may adversely affect the subjects ability to complete the study or its measures or that may pose significant risk to the subject

Answer: A