The global incidence of diabetes is increasing rapidly, with an expected increase of 642 million by 2040, with a corresponding increase in the need for effective management regimens and medications [1]. Blood glucose levels are controlled in people with type 2 diabetes mellitus (T2DM) usually begins with lifestyle and dietary changes, followed by the gradual addition of oral hypoglycemic drugs (OADs). The advent of tresagliptin, a new hypoglycemic drug, has brought good news to patients with T2DM.
Introduction to trafiglistine
In March 2014, Japanese pharmaceutical giant Takeda submitted an application for Trelagliptin (trade name Zafatek), a new drug used to treat T2DM. In March 2015, the drug was approved and marketed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. Trafiglitin is a novel orally active, highly selective dipeptidyl peptidase (DPP-4) inhibitor, also known as a T cell activated antigen CD26 inhibitor[2]. Currently, in the treatment of type 2 diabetes, if the glycemic target is not metformin alone, it is recommended to use a DPP-4 inhibitor as an add-on treatment to metformin. Dpp-4 inhibitors are also recommended when metformin plus sulfonylureas, thiazolidinediones, sodium-glucose co-transporter2 inhibitors, or insulin fail to achieve glycemic control.
Mechanism of action of trafiglitine
DPP-4 enzymes are involved in inactivation of incretin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulin-stimulating polypeptides (GIP), which assist in regulating glucose homeostasis by increasing insulin biosynthesis and secretion and inhibiting glucagon secretion. Thus, by inhibiting the DPP-4 enzyme, DPP-4 inhibitors can elevate insulin levels[3].
Trelogliptin is a potent DPP-4 inhibitor, and in in vitro studies in human plasma, a concentration of 1.3 nmol/L is required for trafiglitine to produce a 50% inhibitory effect (IC50), compared to 5.3 nmol/L for allogagliptin. In a randomized, double-blind, 12-week clinical study of patients with T2DM whose diet and exercise therapy were poorly controlled (7 days of DPP-4 inhibition, the 100 mg tripagliptin (i.e., the usual clinical dose) had an average of 77.4% of DPP-4 inhibition, compared with allogliptin inhibition of 53.4%. It can be seen that the effective rate of trafiglitin is better than that of other similar drugs.
Oral hypoglycemic drugs are an important means of treating T2DM. The clinical application of biguanides, sulfonylureas and thiazolidinediones has played an important role in the prevention and treatment of diabetes. However, it should not be ignored that some traditional drugs may cause symptoms such as hypoglycemia, weight gain, cardiovascular side effects and secondary drug failure to varying degrees, which affects blood glucose control in patients with T2MD to a certain extent. Due to the unique mechanism of action, accurate efficacy, mild hypoglycemic effect, small impact on body weight, and good cardiovascular safety, it is recommended to be compatible with other types of hypoglycemic drugs to achieve complementary advantages, thereby maximizing the safety and effectiveness of treatment. And taking tresagliptin does not cause hypoglycemia, because trelogliptin is a DPP-4 inhibitor, such hypoglycemic drugs only work when blood sugar rises after eating, and do not produce hypoglycemic effects when the glycemic index is normal.
Characteristics of trafiglistine
A total of eight DPP-4 inhibitors are currently approved worldwide for the treatment of type 2 diabetes: sitagliptin, verdaglitine, allogigliptin, lifiliptin, tinigliptin, anagliptin, saxliptin, and geegliptin. Although DPP-4 inhibitors are highly bioavailable, well tolerated, weight neutral, and long-term effective, early DPP-4 inhibitors require one or two doses per day, which may reduce patient compliance. In contrast, trafiglitin only needs to be administered once a week.
Data suggest [4] that patients have a positive attitude towards weekly medications and expect greater convenience, better adherence, and better quality of life (QoL). Studies have shown that poor drug adherence is associated with poor glycemic control, increased economic burden, and increased mortality, so improving patient adherence to medication is important. The American Diabetes Association Standards of Medical Care for Diabetes advocate a patient-centered approach to diabetes care to help healthcare providers identify barriers to adherence to treatment and to help guide the choice of medications. Treatment adherence disorder in patients with T2DM is mainly caused by protocol complexity or frequency of administration, so reducing the frequency of administration can improve treatment adherence. As the world's first weekly oral hypoglycemic drug on the market, the drug advantage of "ultra-long standby" will undoubtedly provide better treatment options for diabetic patients. In addition, it has been reported that trafiglitin also has weight loss effects.
Indications and contraindications to triplastine
Indications: Patients with type 2 diabetes.
Contraindications: (1) Severe ketosis, diabetic coma or pre-coma, type 1 diabetes patients, because infusion, insulin rapid correction of hyperglycemia is necessary, so it is not suitable for the use of tripritin. (2) Patients with serious infections, before and after surgery, and severe trauma. Due to the need for insulin injections to control blood sugar, tretigliptin is not suitable. (3) Patients with severe renal dysfunction or patients with advanced renal failure who need dialysis, because tresagliptin is mainly excreted through the kidneys, delayed excretion may lead to an increase in the blood concentration of strepagliptin. (4) Patients with a history of allergy to trafiglistine.
Dosage and usage of trafiglistine
(1) This drug is taken once a week, on the same day of the week. (2) If the drug is missed on the scheduled date, it will be taken within this week and resumed on the scheduled date next week. (3) If the dosage is excessive due to various reasons, please contact the attending doctor quickly. (4) If there is a attack of gout during the period of taking this drug, please do not arbitrarily increase or decrease the dosage or terminate the medication, please contact the attending doctor. (5) Without the doctor's instructions, please do not stop taking the medicine without authorization.
Adverse reactions of trafiglistine
In a phase III clinical trial in patients with T2DM (NCT0163207), the tolerance to taking tragliglitin once a week was roughly similar to that of allogagliptin and placebo once a day. Throughout the 24-week trial, 5 percent of patients took 100 mg of triplaglitin once a week, 8 percent took 25 mg of allogagliptin once a day, and 6 percent took a placebo to observe treatment-related, treatment-urgent adverse events in each group. The most commonly reported adverse event in all groups was nasopharyngitis, with nasopharyngitis developing in 23%, 21%, and 18% of patients in each group, respectively. No treatment-related serious adverse events were identified. Compared with one patient in the allogagliptin group, no patients in the trilogliptin group developed hypoglycemia. There were no clinically relevant differences between treatment groups in terms of ECG results, vital signs, or laboratory tests. Overall, the safety profile of triprigliptin is superior to that of comparable DPP-4 drugs.
Domestic listing of trafiglistine
At present, triagliptin has not been approved for listing in Chinese mainland and Hong Kong, Macao and Taiwan, and it is a pity that domestic patients with indications have limited access to the drug, and domestic patients in need can obtain more relevant information and information through overseas medical service institutions (such as medical companion travel). In addition, Bangladesh has listed generic drugs of trafiglitine, produced by well-known pharmaceutical companies Bikang and Yaopin International, whose efficacy and usage are consistent with those of Japanese tragnatidine.
Outlook and outlook
In the past 20 years, despite the advent of a new line of oral hypoglycemic drugs and insulin preparations, type 2 diabetes has not been effectively controlled. The marketing of new long-acting oral DPP-4 inhibitors is expected to improve the clinical value and status of DPP-4 inhibitors, as they only need to be administered once a week, thereby improving patient convenience and medication compliance. There are many types of oral hypoglycemic drugs, but the "ultra-long standby" advantage of terraglitin provides a better treatment option for diabetics and is expected to stand out in the highly competitive oral hypoglycemic drug market with its unique advantages.