Identify Potential Subjects
History of type 2 diabetes mellitus on stable doses of either monotherapy or dual
combination therapy with metformin, pioglitazone, or a sulfonylurea OR a stable
dose of insulin (±20%) alone or with metformin
HbA1c 6.5% (48 mmol/mol) to 8.0% (64 mmol/mol) within prior 3 months
Ensure subject meets all inclusion/exclusion criteria
Obtain serum HbA1c ≥ 6.5% (48 mmol/mol) and ≤ 8.0% (64 mmol/mol)
Sitagliptin or Placebo
Subject will receive sitagliptin 50mg, 100mg, or placebo
Confirm the genetics and biomarkers informed consent has been obtained
Then visits every 6 months until study concludes
After first year subjects will be contacted by phone once between each study visit
Inclusion Criteria Exclusion Criteria 1. Subject has type 2 diabetes mel itus with HbA1c of ≥ 6.5% (48 mmol/mol) 7. Subject has a history of type 1 diabetes mel itus or a history of
and ≤ 8.0% (64 mmol/mol). HbA1c must be documented within 3 months
prior to study enrol ment) while receiving:
8. Subject has a history of ≥ 2 episodes of severe hypoglycemia during
• metformin, pioglitazone, or a sulfonylurea as monotherapy or any dual
the 12 months prior to enrol ment. Severe hypoglycemia (hypoglycemia
combination of metformin, pioglitazone, or a sulfonylurea continuously
requiring assistance) refers to instances in which the subject was
without alteration in dose for at least 3 months
sufficiently disoriented or incapacitated as to require help from either
Note: Subjects who have received insulin for only a short period (i.e.,
another individual or from medical personnel (whether or not this
less than 14 days) during a hospitalization or for the management of
acute il ness will not be excluded for that reason. 9. Subject has taken an approved or investigational DPP-4 inhibitor agent
(e.g., sitagliptin, alogliptin, saxagliptin, or vildagliptin), or GLP-1 analogue
• a stable dose of insulin (±20% of the scheduled total daily insulin dose)
(e.g., exenatide, exenatide LAR, or liraglutide), or a thiazolidinedione other
either alone or in combination with a stable dose of metformin for at
than pioglitazone within the past 3 months. 10. Subject has cirrhosis of the liver, as assessed by medical history.
The use of supplemental/sliding scale insulin during the prior three
11. Subject is enrol ed in another experimental protocol which involves the
months is permissible, as long as the total daily insulin dose is within
use of an investigational drug or device, or an intervention that would
±20% of the scheduled total daily insulin dose.
interfere with the conduct of the trial. Note: Subjects who have required modification of their usual insulin daily 12. Subject has a planned or anticipated revascularization procedure.
dose for a short period (i.e., less than 14 days) during a hospitalization or for the management of acute il ness will not be excluded for that reason. 13. Pregnancy or planned pregnancy during the trial period. 2. Subject is able to see a usual care provider at least twice a year. 14. Subject has medical history that indicates a life expectancy of < 2 years
or might limit the individual’s ability to take trial treatments for the duration
3. Subject is ≥ 50 years of age with preexisting vascular disease, defined as
having any one of the fol owing:• History of a major clinical manifestation of coronary artery disease
15. Subject has a history or current evidence of any condition, therapy,
(i.e., myocardial infarction, surgical or percutaneous [bal oon and/or
lab abnormality, or other circumstance which, in the opinion of the
stent] coronary revascularization procedure, or coronary angiography
investigator or coordinator, might pose a risk to the subject, make
showing at least one stenosis ≥ 50% in a major epicardial artery or
participation not in the subject’s best interest, confound the results of the
study (e.g., if subject cannot comply with requirements of the study), or interfere with the subject’s participation for the full duration of the study.
• Ischemic cerebrovascular disease, including:
— History of ischemic stroke. Strokes not known to be hemorrhagic will
16. Subject has an estimated GFR (calculated based on serum creatinine via
the MDRD formula) of < 30 mL/min/1.73 m2.
— History of carotid arterial disease as documented by ≥ 50 % stenosis
17. Subject has a known al ergy or intolerance to sitagliptin.
documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography, with or without symptoms of neurologic deficit. 18. Subject has previously been enrol ed in this trial.
• Atherosclerotic peripheral arterial disease, as documented by objective
evidence such as amputation due to vascular disease, current symptoms of intermittent claudication confirmed by an ankle-brachial pressure index or toe brachial pressure index less than 0.9 or history of surgical or percutaneous revascularization procedure. To learn more or find out if your subject might be eligible call: 4. Female subjects agree to use an effective method of contraception or
must not otherwise be at risk of becoming pregnant.
5. Subject understands the study procedures, alternative treatments
available, and the risks involved with the study, and voluntarily agrees to participate by providing written informed consent.
6. Subject agrees to provide permission to obtain all medical records
necessary for complete data ascertainment during the fol ow-up period.
Der ökonomische Wert der biologischen Vielfalt Wirtschaftswissenschaftliche Fakultät, Universität HeidelbergGrabengasse 14, D-69117 Heidelberg, [email protected] in: Bayerische Akademie für Naturschutz und Landschaftspflege (Hrsg.). Warumbrauchen wir einen flächendeckenden Biotopverbund? Grundlagen zum Verständnis der bio-logischen Mannigfaltigkeit, ihrer ökologischen Be
Ethical issues involving children 1. Preamble Children have unique ethical characteristics, as they are the only class of people who may be discriminated against legally. As minors they are judged not capable of running their own affairs, which are left to adults, normal y parents, to act as guardians for them. Historical y children have had minimal legal rights, with their paren