Dr. Ahmed
Trelagliptin is a DPP-IV Inhibitor, developed by Takeda Pharma under the brand name, Zafatek.
Trelagliptin (Zafatek) is approved in Japan. However, the manufacturers have not sought its approval in the US and European markets because of financial issues and higher costs of obtaining approval.
It was first approved in Japan on 26th March 2015.
What is Trelagliptin (Zafatek)?
Trelagliptin succinate is a highly selective longest-acting oral DPP-IV inhibitor. It is also called T-cell activation antigen CD26.
It is a potent and selective DPP-IV inhibitor. Notably, the DPP-IV enzyme rapidly degrades the endogenous incretins including GIP (Glucose-dependent insulinotropic peptide) and GLP-1 (Glucagon-like Peptide).
Trelagliptin, by blocking the DPP-IV enzyme, increases the half-life of the incretins which effectively lowers blood glucose.
In addition, it is not associated with significant hypoglycemia or weight gain.
Trelagliptin inhibits 77.4% of the activity of DPP-IV enzymes after 7 days of its administration, when given at a dose of 100 mg per week [Ref].
Furthermore, Trelagliptin also increases insulin levels, C-peptide levels, and HOMA, all indicative of Beta-cell preservation.
Trelagliptin was found comparable with Alogliptin except for post-meal glucose tolerance and GLP-1 levels following a meal tolerance test where Alogliptin was superior [Ref].
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Trelagliptin Pharmacology:
Trelagliptin is a long-acting, once-weekly potent diabetes pill. In clinical trials, when administered before breakfast, it reached peak serum concentrations in 1 to 1.5 hours.
It has a half-life of 38.44–54.26 hours. DPP-IV inhibition is maintained throughout the week with a once-weekly administration [Ref]
Trelagliptin is primarily metabolized by the enzyme, cytochrome P450 (CYP) 2D6, and excreted mainly by the kidneys (76%).
Trelagliptin should not be used in patients with a creatinine clearance of <30 mL/min and end-stage renal failure.
In patients with moderate renal impairment (CrCl of 30 to <50 mL/min), the dosage should be reduced to half, i.e., 50 mg once weekly.
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Trelagliptin Vs Alogliptin:
In Phase III, Japanese Clinical Trial, Trelagliptin in a dose of 100 mg weekly was non-inferior to 25 mg per day of alogliptin [Ref]
| Treatment Group | Mean Baseline HbA1c (%) | Mean Change in HbA1c (%) |
| Trelagliptin | 7.73 | -0.33 |
| Alogliptin | 7.87 | -0.45 |
Trelagliptin was found statistically non-inferior to Alogliptin in lowering HbA1C levels after 24 weeks.
The drug has not been directly compared with other DPP-IV inhibitors. In addition, unlike other DPP-IV inhibitors, it has not been cleared in patients with atherosclerotic cardiovascular disease.
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Trelagliptin Dose:
The usual recommended dose is 100 mg once a week. The dose may be reduced in patients who are intolerant to DPP-IV inhibitors or who have moderate renal impairment.
Because Trelagliptin is a weak DPP-IV, it is recommended as an add-on to metformin, SGLT2 (Dapagliflozin, Empagliflozin, or Canagliflozin), Sulfonylureas (Glipizide, Glimepiride, or Glyburide), Thiazolideneddiones (Pioglitazone), or Insulin.
It should not be used in patients who are on another DPP-IV inhibitor like Sitagliptin or Vildagliptin, GLP-1 analogs such as Semaglutide (Ozempic, Rybelsus, or Wegovy), Trulicity (Dulaglutide), Victoza (Liraglutide), or those on Dual GLP-1 and GIP analogs, Mounjaro (Tirzepatide)
In addition, it is preferred in patients who have an A1C of 6 to 8%. For those with an A1C above 8%, a more potent once-daily DPP-IV inhibitor should be used.
Trelagliptin can be taken once daily before breakfast. For patients who have severe gastrointestinal side effects associated with Trelagliptin, the timings of administration may be changed.
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Who should not take Trelagliptin?
Trelagliptin should not be used by patients who have any of the following medical conditions:
Pancreatitis:
Like all other DPP-IV inhibitors, Trelagliptin may cause acute pancreatitis. Patients at risk of acute pancreatitis or those who have recurrent pancreatitis should not be prescribed Trelagliptin.
Medullary thyroid cancer:
GLP-1 and drugs which increase the levels of GLP-1 such as DPP-IV inhibitors are contraindicated in patients who have a personal or a family history of medullary thyroid cancer or MEN-2 syndrome.
Allergy:
All patients allergic to Trelagiptin should avoid using it.
Severe Renal Impairment:
It is not indicated in patients with severe renal impairment such as those with a CrCl of less than 30 ml/minute.
Type 1 Diabetes:
Trelagliptin is not for use in patients with Type 1 diabetes. It should also be avoided in Type 3C diabetes.
Acute hospital settings:
Trelagliptin should be avoided in acute hospital settings such as patients who are undergoing surgery or those who have a hyperglycemic emergency like DKA or HHS.
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