Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-Center, Randomized, Placebo Controlled, Double Blind Trial of Metformin in Obese Adolescents.
Brief Summary: This study will determine if the drug metformin, coupled with diet and exercise counseling, will help obese adolescents lose weight.


Options:
A: * INCLUSION CRITERIA:

Volunteers will qualify if they meet the following criteria.

* Female.
* Age 12 17 years.
* BMI between 75th and 97th percentile.
* English speaking.
* Good general health.
* Participants must have normal laboratory testing, including negative urine glucose and normal electrolytes, hepatic, and thyroid function, or they will be referred for treatment.

EXCLUSION CRITERIA:

Individuals will be excluded (and referred to non-experimental treatment programs as needed):

* Presence of major illnesses: renal, hepatic, gastrointestinal, most endocrinologic (e.g., Cushing syndrome, hyper- or hypothyroidism), hematological problems or pulmonary disorders (other than asthma not requiring continuous medication). Non-serious medical illnesses, such as seasonal allergies, will be reviewed on a case-by-case basis.
* Presence of an obesity-related medical complication that would require a more aggressive weight loss intervention approach. Such comorbidities include hyperlipidemia (LDL-cholesterol greater than 160 mg/dL), hypertension (defined by age-, sex-, and height- specific standards fasting hyperglycemia (fasting glucose greater than 100 mg/dL) and nonalcoholic steatohepatitis (ALT above NIH Clinical Center laboratory norms with consistent radiologic findings and absence of another cause such as infectious hepatitis).
* Regular use of prescription medications. Oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study. Individuals taking medications for most conditions will be excluded, but medication use for non-serious conditions (e.g., acne) will be considered on a case-by-case basis. In particular, participants currently prescribed SSRIs, neuroleptics, tricyclics, stimulants, or any medication known to affect body weight or eating will be excluded.
* Current involvement in psychotherapy or a structured weight loss program.
* Weight loss during the past 2 months for any reason exceeding 3 per cent of body weight.
* Pregnant or recently pregnant girls (within 1 year of delivery).
* History of an eating disorder or a current eating disorder (other than binge eating disorder) as determined by medical history or if uncovered during the study s structured clinical interviews. Subjects found to have an eating disorder other than binge eating disorder at baseline will be referred to mental health specialists for further evaluation and treatment.
* Current pregnancy or breast feeding. A negative pregnancy test before starting the study will be required. Because pregnancy is a state in which weight gain is expected and appropriate, pregnant individuals would not be suitable for this study. Sexually active females must be using an effective form of birth control. These methods include total abstinence (no sex), oral contraceptives ( the pill ), an intrauterine device (IUD), levonogestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended. Should a participant in the IPT-WG group become pregnant during the 12 weeks of therapy, she will be excluded from the group sessions. The girl s IPT-WG therapists will closely assist her in obtaining an appropriate referral to a community mental healthcare provider. The IPT-WG leaders will request a release of information so that they may communicate with the community therapist in order to facilitate a smooth transition for the girl.
* Individuals who have DSM-IV-TR major depressive disorder, psychoses, current substance or alcohol abuse, conduct disorder, or a diagnosed psychiatric disorder that, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study. Individuals whose parents or guardians have current substance abuse or a diagnosed psychiatric disorder or other condition that, in the opinion of the investigators, would impede adherence with the study.
* Inability to participate in a group due to psychiatric or cognitive functioning. School placement (e.g. grade level) will be used as an estimate of cognitive functioning. The decision to include or exclude subjects for this reason is left entirely to the discretion of the investigators.
* Any other condition in the adolescent or her parents or guardians that, in the opinion of the investigators, would impede compliance or possibly hinder completion of the study.
B: Inclusion Criteria:

* You are healthy.
* You are not pregnant or nursing.
* You are between 18 and 60 years of age.
* You have a body mass index, calculated from your height and weight, of 30 to 40 kg/m2.

Exclusion Criteria:

* You take chronic medications except hormone replacement or contraception.
* You are a woman and are unwilling to use effective contraception during the trial.
* You have blood pressure higher than 150/90.
* You have heart disease.
* You have urinary symptoms from an enlarged prostate.
* You have gained or lost more than 10 pounds in the last 6 months.
* You have used a monoamine oxidase inhibitor medication in the last month.
* You have high or low thyroid function that has not been controlled in the normal range for at least 2 months.
* You have heart disease or a history of stroke.
* You have a known sensitivity to E. coli or E. coli derived products.
C: Inclusion Criteria:

A. General inclusion criteria

1. Ten to 20 years of age.
2. Pubertal (Tanner stages 2-5, by examination).
3. Hemoglobin A1c level of \> 8.0% in the 6 months prior to enrollment.
4. All subjects must have access to a computer.

B. Specific inclusion criteria: \[Subjects could have either #1, or #2\].

1. Subjects with clinical and biochemical features of T2DM of \> 6mo duration who also have positive T1DM antibodies

   * Clinical features: acanthosis nigricans, BMI \>85%
   * Biochemical: evidence of insulin resistance at diagnosis
   * fasting insulin \>27 uIU/mL(normal range 6-27) at a fasting blood glucose of ≥ 126 mg/dL, or
   * fasting c-peptide level of \> 7.1 ng/mL (normal range 0.9 - 7.1), or
   * Homeostasis model of insulin resistance of \>3.16
2. Patients with T1DM of \> one yr duration with BMI \>85%

   * Presentation with ketoacidosis at diagnosis
   * C-peptide \<0.9 ng/mL (normal range 0.9 - 7.1),or (insulin \< 6 uIU/mL) (NR 6-27) at diagnosis (when blood glucose is ≥ 126 mg/dL)
   * Can be antibody positive or negative
   * Increased insulin requirement (\>2 Units/kg/day)

Exclusion Criteria:

1. Subjects on weight altering medications, such as orlistat.
2. Subjects with eating disorder
3. Subjects on medications other than insulin and or metformin that may affect blood glucose level.
4. Subjects with abnormal hepatic function tests.
5. Subjects with nephropathy, defined in this case as an overnight albumin excretion rate of \>200 mcg/min using a first morning urine sample collection.
6. Subjects with recurrent diabetes ketoacidosis (more than 2 episodes in the past 12 months), or recurrent severe hypoglycemia (more than 2 episodes of hypoglycemia with altered level of consciousness, requiring assistance to treat in the past year).
7. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures.
8. Known or suspected allergy to metformin.
9. The receipt of any investigational drug within 6 months prior to this trial.
10. Active malignant neoplasms.
11. No access to a computer.
12. Subjects currently taking metformin for clinical purposes are not eligible to be enrolled in this study.
D: Inclusion Criteria:

* Subjects must be between the ages of 13.00 and 17.99 at week 0 (Baseline).
* Subjects must have a BMI ≥ 95th percentile for age and gender using the CDC data (see Appendix), but must weigh less than 300 pounds (\<136 kilograms) when measured during the initial physical exam at week 0 (Baseline). BMI will be calculated as follows; weight in kilograms  \[height in meters\]2. This cutoff has been established due to the weight-bearing limits of the table used in performing the DXA scan. Once enrolled, if a subject's weight progresses above 300 pounds, s/he may continue in the study whether it is possible to perform DXA or not.
* Completion of informed consent/assent process

Exclusion Criteria:

* Known diabetes as defined by the American Diabetes Association criteria
* Prior drug therapy to treat diabetes or insulin insensitivity, including any form of insulin or insulin analogs; or any oral antidiabetic medication; acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, pioglitazone, repaglinide, rosiglitazone, tolazamide, tolbutamide or troglitazone.
* Prior use of drugs to aid in weight loss, including but not limited to: Benzphetamine Hcl, Diethylpropion Hcl, Fenfluramine Hcl, Phendimetrazine Tartrate, Phentermine Hcl, Orlistat, Sibutramine Hcl Monohydrate, Didrex, Tenuate, Pondimin, Bontril-SR, Adipex-P, Fastin, Ionamin, Phentrol, Xenical, Meridia.
* Subject is currently taking the following medications at the time of the Screening visit: Cimetidine, amiloride, digoxin, furosemide, morphine, nifedipine, procainamide, ranitidine, triamterene, trimethoprim, vancomycin and quinidine, as these medications may increase metformin levels.
* Subjects will be excluded from the study if they have taken prescription-strength glucocorticoids (by any route) within three months of the screening visit. Topical glucocorticoids are acceptable if their strength is no greater than the equivalent of 1% hydrocortisone cream.
* History of any syndrome or medical disorder associated with significant obesity, including but not limited to: Prader Willi Syndrome, Bardet-Biedl Syndrome, Cohen Syndrome, Cushing syndrome or disease.
* Prior surgical therapy for obesity
* Subject to be excluded if s/he has attended a formal weight loss program within 6 months prior to the Screening visit.
* In the 6 months prior to Screening, subject has consumed alcohol more frequently than twice per week and/or subject has had more than three alcohol-containing beverages in a 24 hour period.
* Elevated creatinine (\> 1.2 mg/dl)
* Untreated disorders of thyroid function
* Elevated liver enzymes (Alanine Aminotransferase \[ALT\] or Aspartate Aminotransferase \[AST\]) \> 80 (approximately 2 times upper limit of normal)
* Mobility impairment that prevents full participation in recommended physical activity
* Other serious medical condition that the Principal Investigator or Lead Site Investigator determines may put the patient at undue risk if enrolled in the study
* Unable to comply with the protocol in the opinion of the Principal Investigator or the Lead Site Investigator
* Subjects with child-bearing potential who are unwilling to remain abstinent or use an effective method of birth control
* Previous pregnancy

Answer: D