Type 1 or 2 diabetes requiring anti-hyperglycemic medication (e.g. metformin, glipizide, insulin)

Patients currently taking metformin will be eligible

Patients may not be taking metformin for a reason other than study participation

Patients must not receive metformin for at least 5 days prior to enrollment and for the duration of study treatment

Subjects may have diabetes mellitus but must not be taking metformin

Known hypersensitivity or intolerance to metformin

Known hypersensitivity to metformin

Subjects currently treated with metformin and/or bicalutamide or who have been treated with metformin and/or bicalutamide in the past 6 months

Prior or current use of metformin within the past 3 months

History of hypersensitivity to metformin or history of discontinuation secondary to attributed adverse effects

Chronic (daily use for > 1 month) use of cimetidine (significant increase in metformin concentration and risk of lactic acidosis)

Iodinated contrast agents used in prior 48 hours (significant increase in metformin concentration and risk of lactic acidosis)

Subjects receiving metformin or other agents known to increase risk of lactic acidosis.

Subjects may have diabetes mellitus but must not be taking metformin or have previously taken metformin within previous year

Known hypersensitivity or intolerance to metformin

Subjects who are pregnant or breastfeeding, or may become pregnant during metformin and doxycycline administration

Subjects on metformin or doxycycline for any reason during the preceding 4 weeks

Diabetic subjects that are managed by taking metformin or insulin

Subjects who have received iodinated contrast dye must wait 12 hours prior to starting metformin; if a computed tomography (CT) scan with contrast is scheduled after screening and consent, the metformin cannot be taken until after the CT with contrast has been completed and they have waited 12 hours

Patient with prior allergic reaction to metformin, doxycycline, or any other tetracycline antibiotic in the past

Patient is on medications that are contraindicated with metformin or doxycycline under current Food and Drug Administration (FDA) recommendations; the following is a list of medications identified as class D (consider therapy modification) when treatment with metformin or doxycycline is considered:\r\n* Class D:\r\n** Bismuth Subsalicylate\r\n** Cimetidine\r\n** Iodinated contrast agents\r\n** Somatropin

Both arms: patients should not have received metformin within 6 months prior to registration\r\n* Arm B: patients who were on metformin while on PD-1/PD-L1 inhibitors are not eligible

Patients with known diabetes whose glucose control or general health condition may be adversely affected by the use of metformin as per the study protocol as deemed by either the study investigator or endocrinologist are excluded

Patients must not have any of the following contraindications to metformin:\r\n* Hypersensitivity to metformin or any component of the formulation\r\n* Kidney dysfunction or abnormal creatinine (Cr < 2 ng/mL) from any cause\r\n* Acute or metabolic acidosis

Patients must be at least 5 half-lives beyond previous treatment with metformin and currently not taking metformin

History of hypersensitivity to TAK-228 or metformin

Subjects who are pregnant or breastfeeding or may become pregnant during metformin and doxycycline administration

Subjects on metformin or doxycycline for any reason during the preceding 4 weeks

Diabetic subjects are eligible if they are not taking metformin or insulin

Subjects who have received iodinated contrast dye must wait 12 hours prior to starting Metformin; if a computed tomography (CT) scan with contrast is scheduled after screening and consent, the metformin cannot be taken until after the CT with contrast has been completed and they have waited 12 hours

Prior allergic reaction to metformin, doxycycline, or any other tetracycline antibiotic in the past

Patient is on medications that are contraindicated with metformin or doxycycline under current Food and Drug Administration (FDA) recommendations; the following is a list of medications identified as class D (consider therapy modification) when treatment with metformin or doxycycline is considered\r\n* Class D \r\n** Bismuth Subsalicylate\r\n** Cimetidine\r\n** Iodinated contrast agents\r\n** Somatropin

No previous treatment with vandetanib; previous or ongoing treatment with metformin is allowed

Known serious allergic reaction to vandetanib or metformin

Known sulfonylurea treatment within 7 days prior to registration; sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); and glibornuride (Glutril)

Patients who are currently taking metformin; prior metformin use is allowed if last dose was 3 months previous to this trial

History of allergic reactions attributed to metformin or other biguinides

Currently taking metformin, sulfonyureas, thiazolidenediones or insulin for any reason

History of hypersensitivity to temsirolimus or metformin

Subjects with known diabetes and those taking metformin, sulfonylureas, thiazolidinediones or insulin for any reason

Patients with diabetes on metformin; patients with diabetes and not on metformin will be eligible if it is deemed safe after consultation with the patient physician managing diabetes

Patients taking metformin or digoxin

Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin

Patients must NOT be taking metformin or have been on metformin in the past 6 months

Diabetic patients who are on metformin are eligible as long as they have been on metformin for less than 6 months (estimated 6 months or less duration of metformin therapy from start of metformin to enrollment on study)

Current use of metformin for more than 6 months prior to enrollment on study

Patients with type II diabetes currently already on metformin

Patients who received aspirin or metformin within the past 28 days

Patients taking medications with known interactions with metformin or aspirin

Patients with history of allergic reaction to metformin

Currently taking metformin, sulfonylureas, thiazolidinediones, or insulin for any reason

Have no contraindications to short-term metformin therapy

Need to be able to undergo metformin treatment for a duration of 12 weeks (+/- 7 days) prior to repeat endometrial biopsy

Are currently taking metformin or have taken metformin in the past 6 months or have a history of an allergic reaction or intolerance at any time to metformin

Are taking a drug that may significantly interact or influence the metabolism of metformin

Prior metformin treatment OR EGFR targeted therapy

Patients taking Metformin for any reason within 30 days of enrollment to the study

Subjects who are pregnant or may become pregnant during metformin administration

Subjects on metformin for any reason during the preceding 4 weeks

Diabetic subjects are eligible if they are not taking metformin, insulin or sulfonylureas

Subjects who have received iodinated contrast dye less than 48 hours prior to screening meet a temporary exclusion criteria to receive metformin; these patients cannot start investigational metformin until 48 hours have elapsed from contrast administration; subjects who are scheduled for iodinated contrast dye administration within 48 hours of definitive surgery are excluded

Currently taking metformin, sulfonylureas, thiazolidinedione, insulin, or other antidiabetic drugs for any reason

Known hypersensitivity or intolerance to metformin

Patients already receiving metformin or anti-diabetic medications are INELIGIBLE

If any patient develops symptomatic diabetes requiring drug therapy, he must receive such a therapy, which may include metformin; this must be documented, and the patient will not continue on the study

Metformin use in the last 6 months

A known hypersensitivity to metformin

Known intolerance to doxorubicin, metformin, or vincristine

Patients who have a need to continue hydroxyurea while on study\r\n* Please note: patients may continue on hydroxyurea only until the first dose of metformin is to be given

Known hypersensitivity to metformin or statins

Patients currently treated with metformin or a statin or who have been treated with metformin or a statin in the past 6 months are ineligible for this study

Subjects who are pregnant or may become pregnant during metformin administration in accordance with radioactive iodine treatment guidelines

Subjects on metformin for any reason during the preceding 4 weeks

Diabetic subjects are eligible if they are not taking metformin, insulin or sulfonylureas

Subjects who have received iodinated contrast dye; metformin treatment can be started the day after subjects complete iodinated contrast treatment; if a computed tomography (CT) scan with contrast is scheduled after screening and consent, the metformin treatment should be stopped the day before iodinated contrast administration; metformin can be resumed on the day after last iodinated contrast was administered to the subject

All medications other than those that may cause myelosuppression are permitted except those that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations

Current metformin therapy

Subjects who are pregnant or may become pregnant during metformin administration; pregnancy testing will be done in conjunction with preradiation protocols

Subjects on metformin for any reason during the preceding 4 weeks

Diabetic subjects are eligible if they are not taking metformin or insulin

Subjects who have received iodinated contrast dye must wait 12 hours prior to starting metformin; if a computed tomography (CT) scan with contrast is scheduled after screening and consent, the metformin cannot be taken until after the CT with contrast has been completed and they have waited 12 hours

All medications are permitted except those that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations

Known hypersensitivity or intolerance to metformin

Patients currently receiving or scheduled to receive a chemotherapy infusion other than adriamycin/cyclophosphamide prior to initiation of the metformin adaptation phase are not eligible; patients who are receiving adriamycin/cyclophosphamide must be scheduled to be at least 8 days post-chemotherapy infusion prior to initiation of the metformin adaptation phase in order to be eligible

Patients who are currently using metformin (eg, Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet)

Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin

Women who have taken metformin within the past 90 days

Current use of any drug (except metformin) or anticipated change in concomitant medication, which the investigator’s opinion could interfere with the glucose metabolism (e.g. systemic corticosteroids).

Currently taking medication that may impact weight (e.g., Synthroid, metformin)

Current or prior regular use of metformin within the past 3 months

History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year

Current use of metformin or other anti-diabetic agents, or hypersensitivity or allergy to metformin

VITAMIN D/METFORMIN SUBARM OF LOW GRADE DYSPLASIA/NO DYSPLASIA ARM:

VITAMIN D/METFORMIN SUBARM OF THE DYSPLASIA/NO DYSPLASIA ARM:

Allergic reaction to metformin

Participants may not be using metformin, cimetidine (Tagamet), furosemide (Lasix), nifedipine (Cardizem), or any other drug contraindicated for use with metformin

Have a history of allergic reactions to metformin or similar drugs

No known hypersensitivity or intolerance to metformin

No current treatment with metformin, sulfonylureas, thiazolidinediones or insulin for any reason

Prior treatment with metformin

Known allergy to metformin or other biguanide (Proguanil)

Participants who are taking metformin at the time of the exam are excluded

Taking metformin (example: Glucophage, Glucovance, Avandamet, Metaglip)

Currently taking Glucophage or Glucovance (metformin)

NORMAL VOLUNTEERS: Be taking metformin, aminoglycosides, other nephrotoxic medications, or daily use of NSAIDs

Patients with type 2 diabetes mellitus (T2DM) being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed

Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery\r\n* Patients do not require a diagnosis of diabetes to be enrolled in the study

All patients must be willing to keep a drug diary indicating the dates and times of metformin administration

History of diabetes that is currently being treated without metformin

Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period

This criterion does not apply to patients taking clinically indicated metformin at the time of study entry

Known hypersensitivity to metformin

Must have been off metformin for at least 2 weeks prior to starting IFN gamma

Participants who are already on treatment with metformin, except when metformin can be held for 4 weeks prior to the start of the study

Diabetic patients are eligible but will be excluded if they are taking metformin, insulin or sulfonilureas