Trelagliptin is indicated for type 2 diabetes mellitus. When the first line treatment of metformin is not achieving the expected glycemic goals.

By inhibiting the activity of dipeptidyl peptidase 4 Trelagliptin inactivates glucagon-like peptide 1 (GLP-1) from secretion from the intestines to the blood via stimulation from oral intake of food, increases GLP-1 blood concentration and promotes blood glucose concentration-dependent insulin secretion from the pancreas.

DPP- 4 Inhibition: Selectively inhibits human plasma DPP-4 activity (IC50 value: 4.2 nmol/l) /in vitro). Moreover, when IC50 value (nmol/L) was compared under similar conditions (in vitro) in order to compare Trelagliptin and alogliptin DPP-4 inhibitory action, values were 1.3 and 5.3 respectively. Type 2 diabetes patients who exhibit insufficient blood glucose control through dietary and exercise measures were given 100 mg of Trelagliptin [once weekly, before meal] for 12 weeks. The results of the double blind, parallel group, placebo controlled comparative study show that 7 daysafter final treatment, the average DPP-4 inhibition rate was 77.4% compared in the Trelagliptin 100 mg group.

Active Type GLP-1 Concentration Elevation: Type 2 diabetes patients who exhibit insufficient blood glucose control through dietary and exercise measures were given 1OOmg of Trelagliptin orally [once weekly, before meal) for 12 weeks. The results of the double-blind, parallel group, placebo-controlled comparative study showed GlP-1 concentrations with meal load tests conducted 12 weeks after administration to be significantly elevated relative to the placebo group.

Glucose Tolerance Improvement: A single, oral dose of Trelagliptin was given to obese type 2 diabetic model organisms (Wister fatty rat) and non-obese type 2 diabetic model organisms (N-STZ-1.5 rat) after 1 night of fasting. Glucose was then given orally 1 hour after drug administration to conduct a glucose load test. Results from the tests revealed a glucose tolerance-improving action.

100 mg of Trelagliptin is administered to adults once weekly by mouth.

Cautions Related to Methods and Dose: For patients with moderate kidney function disease, given that blood drug concentration will elevate due to delayed elimination, reduce dosage with reference to the chart below.

Instruct the patient regarding the following points: This medication is to be takenonce weekly,and on the same day every week. If patient forgets to take medication as scheduled, only take the quantityintended for the time in which the forgotten dose was realized, and then continue dosage according to a newly decided schedule afterwards.

Study subjects meeting any of the following criteria will not be included in this study:

• Patients under treatment with trelagliptin for type 2 diabetes at the start of screening.
• Patients with a diagnosis of type 1 diabetes.
• Patients with severe renal impairment or renal failure (e.g., eGFR < 30 mL/min/1.73 m2 or on dialysis).
• Patients with serious heart disease or a cerebrovascular disorder, or a serious pancreatic, blood, or other disease.
• Patients with a history of gastrointestinal resection.
• Patients with a proliferative diabetic retinopathy.
• Patients with malignancy.
• Patients with a history of hypersensitivity or allergy to DPP-4 inhibitors.
• Patients who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant.
• Patients who may need to add or discontinue concomitant medication or change the dose during the study period.
• Patients who will require treatment with a prohibited concomitant medication during the study period.
• Patients participating in other clinical studies.
• Patients assessed as ineligible for any other reason by the investigators.

Among 901 domestic clinical trial cases up to the time of approval, 103 cases (11.4%) showed clinical results that included abnormalities and side effects. These mainly included hypoglycemia, nasopharyngitis, and elevated lipase.

Given the appearance of serious side effects such as hypoglycemia (0.1~5%), administer medication in conjunction with close observation of patient status. Other DPP-4 inhibitors have been reported to present serious hypoglycemia in combination with Sulfonylurea medications as well as some cases of loss of consciousness. Moreover, decreased blood sugar from the use of this medication, once confirmed, can be remedied by giving sucrose. However, hypoglycemia resulting from a combination with-glucosidaseinhibitors should be treated with fructose.

Acute pancreatitis can occur, so careful observation is called for and sustained, intense abdominal pain, vomiting, and other abnormal symptoms should be followed up with cessation of the drug followed by appropriate measures.

Intestinal Obstructions can occur, so conduct careful observation. If severe constipation, abdominal swelling, sustained abdominal pain, vomiting, or other symptoms are observed, stop treatment and take appropriate measures.

Other Side Effects: Take appropriate actions depending on the situation if the following side effects arise.

Administration to Elderly Patients: Since many geriatric patients generally have lowered kidney function, take note of side effects and administer a cautious dose while sufficiently observing treatment progress.

Administration to pregnant women, lactating women, or for gynecological use: For women who are pregnant or may be pregnant, only administer drug upon fully evaluating the risks and benefits of treatment. The safety of use during pregnancy is not established. There are reports of the drug crossing the placenta in animal (rat) tests. Avoid giving drug to women who are breastfeeding, and stop breastfeeding if drug must be administered.

Administration to children: The safety of this drug in infants with low birth weight, newborn infants, nursing infants, babies, and children under the age of 13 is not established.

Overdose safety information regarding overdose has not been sufficiently collected, for dietary and exercise treatments, as well as metformin-only treatments, or for type 2 diabetes patients in which blood sugar control is not ideal. However, there have been overseas studies in which lOOmg of this drug was taken orally every day over 12 consecutive weeks and side effects did not differ from the placebo group.

Other warnings overseas clinical studies involving single Trelagliptin doses of 800mg reported QT elongation.

No study has performed in patients who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant.

Provide cautious dosage to the following patients: The following patients or circumstances-

• Patients with moderate kidney function disorder
• Patients undergoing treatment with sulfonylurea drugs or insulin medication [there are reports of severe hypotension with use in combination with other DPP-4 inhibitors]
• Hypopituitarism or hypoadrenalism
• Malnutrition, starvation, irregular eating patterns, insufficient eating, or hyposthenia
• Vigorous exercise
• Patients who consume excessive alcohol

Major Warnings-
This drug may cause hypoglycemia when used in combination with other diabetes medications, so thoroughly explain and caution the patient of such risks of hyoglycemia when combining with other medications. There is an increased risk of hypoglycemia particularly when combined with sulfonylurea drugs and insulin medications. Consider reducing the dose of sulfonylurea drugs or insulin medication when used in combination with these drugs in order to lessen the risk of hypoglycemia.

This drug is to be taken orally once per week. Effects may persist even after dosage is ceased, so take sufficient notice of blood sugar volues and side effects. Moreover, evaluate the starting period and dose based on the state of blood sugar management when using other diabetes medications after cessation of this medication.

Only consider application for patients with established diagnosis of diabetes mellitus. Pay attention to conditions that show abnormal sugar resistance, glucosurea, and other symptoms resembling diabetes [renal glucosuriea, thyroid function abnormality, etc.)

Application of this drug should only be considered once diet- and exercise-based diabetes treatments have already been implemented with unsatisfactory results.

During administration of this drug, progress should be sufficiently observed along with quantitative blood sugar measurements, if no results are seen after 2 to 3 months of treatment, consider changing to a more appropriate treatment method.

During dosage maintenance, the medication may no longer become necessary, or the effects of the drug may diminish due to complications with poor nutrition or infectious disease. In such cases, evaluate continuation of normal does, medication selection, etc. upon consideration of dietary volume, blood sugar levels, and presence of infectious symptoms.

Warn patients that work in high places, operate machinery, etc., as low blood sugar can occur.

Clinical results and safety regarding combination with insulin medication has not been investigated.

This drug and GLP-1 receptor agonists both possess the ability to lower blood sugar and assist GLP-1 receptor agonists.There are no clinical study results regarding the combination of these medications, and neither the efficacy nor the safety can be confirmed.

Store at 25°C; excursions permitted to 15°-30°C. Dispense medication in the original container to protect from exposure to high humidity and light. Keep out of the reach of children.