**5. Diabetes mellitus a medical challenge**

2. Study Endpoints: Primary, Key secondary endpoints.

well informed about all aspects of the study.

scientific study team before inclusion in the trial.

7. Trial Visits. General information. Informed Consent

adjustments, drug storage, and accountability.

12. Administrative and Regulatory Details.

years after the end of the study.

Ethical conduct of the study.

recruitment and other important aspects of the investigation.

16. Data analysis / Statistical Methods. Steering Committee, Scientific Committee.

13. Analysis of the End-point.

drug and in some cases for placebo. The goal for blood glucose, glycated

investigation. For example, group 1 (drugs), group 2 (drugs or placebo).

4. Subject/patients:

130 Treatment of Type 2 Diabetes

4.2. Exclusion Criteria. 5. Trial Design and Duration 6. Pre-randomization visit.

8. Follow-up of subjects. 9. Drug supplies.

10. Study Procedures.

11. Data Collection.

study.

14. Quality Control. 15. Committees.

17. Ethical aspects.

3. Evidence of a personally signed and dated informed consent document indicating that the patient has been

4.1. Inclusion Criteria. Subject eligibility should be reviewed and documented by an appropriate qualified

6.1. Randomization visit. Following completion of the run-in period, subjects will be randomized for active

6.2. hemoglobin or other biological parameters has been established by any protocol submitted for

These items include formulation and packaging, preparation and dispensing, administration, doses

The specific procedures, including laboratory test to be performed at all study visits. Blood draw must be taken in the morning before 12.00 p.m.; ECG, and others parameters, and, in some cases, X-Ray, or other diagnostic imaging procedures. It must be taken in the same day in order to offer more facilities to patients.

The case report forms to be used are designed to collect an appropriate amount of data necessary for the

The Coordinating Office and investigators will follow the principles of *Good Clinical Practice*. According with law, the trial information will be recorded in all electronic or papers forms and keep it during 10-15

. The Committee structure is very similar from one trial to another. The members of the committees will be detailed at the end of the publication, and also an appendix for acknowledgments will be provided On the other side, the members of the Data Monitoring Committee are not investigators of the trial. A National Coordinator for each country is desirable. The Steering Committee is responsible for agreeing the protocol, any change to the protocol and for the general running of the trial. The monitoring and statistical Committee (Data Monitoring Committee) will be responsible for quality control of the data, monitoring

Type 2 Diabetes Mellitus (DM) accounts for more than 90% of all diabetes. This disorder is a worldwide epidemic affecting an estimate of 366 million adults aged 20-79 years, according to data from 2011. The prevalence of this metabolic disorder in adult population is expected to go from 8.3% to an estimate of 9.9% by 2030, resulting in an increase in the number of people with diabetes worldwide up to 552 million.

Unfortunately, many people are unaware that they have diabetes. The figures reveal that over six million Americans are undiagnosed. The proportion is very similar in other Western countries. The disease is commonly discovered when the typical symptoms, previously mentioned, are developed and high blood sugar levels are found, defined as a daytime level greater than 200 milligrams per deciliter or a fasting level greater than 120 milligrams per deciliter. In some cases oral glucose tolerance test is required for undiagnosed people.

The relationship between glycemia and the risk of microvascular disease has been wellestablished. The results of the *Diabetes Control and Complications Trial* (DCCT), the *United Kingdom Prospective Diabetes Study* (UKPDS) [7], and the *Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation* (ADVANCE) *Trial* [8], demon‐ strated that patients with DM treated to lower glycemic targets have reduced rates of micro‐ vascular complications (e.g., retinopathy and nephropathy). However, results of more recent trials including ADVANCE, the *Action to Control Cardiovascular Risk in Diabetes* (ACCORD), and *Veterans Affairs Diabetes Trial* (VADT) [9] aimed for an A1c <6.0, and ADVANCE aimed for an A1c<6.5%. These and other data have more recently led to a movement away from blanket prescriptive targets for A1C (e.g. <6.5% or <7%) and to the growing consensus among diabetes experts that glycemic targets and glucose-lowering therapies should be individual‐ ized. Age, weight, and comorbidities such as established cardiovascular disease, and kidney or liver disease are among the patient's factors that should be considered by physicians, nurses, family, and others. Diet, exercise, and education remain the main stay of treatment for diabetic patients in order to avoid serious complications [10]. In addition, there are several classes of oral antihyperglycemic agents (AHA) available for use as monotherapy or as combination therapy, including the dipeptidylpeptidase (DPP-4) inhibitor class, which is administered either once or twice daily [11, 12, 13].

In general, medication adherence in chronic diseases, such as diabetes may be low, ranging from 36% to 93%. Side effects associated with oral antihyperglycemic agents therapies, including hypoglycemia, (sulfonylureas, meglitinides, insulin), weight gain, (sulfonylureas, meglitinides, insulin, hypersensitivity reactions, thiazolidinediones) and gastrointestinal intolerance, nausea, vomiting (metformin, alpha-glucosidase inhibitors) are common patientreported reasons for poor medication adherence. Many studies have demonstrated that adherence to antihyperglycemic agents therapy is related to the number of pills prescribed: several studies have reported that, when patients were prescribed multiple drugs to treat diabetes, adherence significantly decreased, with reductions ranging from 15% to 54%. A prospective study showed a mean adherence of 79% for a triple-daily regimen, 65% for a twicedaily regimen, and 38% for a thrice-daily regimen. Some data from osteoporosis therapies indicate that, compared to a once-daily regimen, a once-weekly treatment can increase medication adherence and compliance. Therefore, a once-weekly oral AHA therapy might improve treatment adherence in many patients with these metabolic disorders.
