Search. Learn. Save

Platform for Pharmaceutical Products for Healthcare Professionals
Search By
☰ Generic Formulas

Generic Formulas X

Trelagliptin

Trelagliptin: A Once-Weekly Revolution in Diabetes Management

Introduction

Type 2 diabetes mellitus (T2DM) is a global health concern, affecting millions of individuals and posing significant risks for complications including cardiovascular disease, kidney failure, neuropathy, and retinopathy. Traditional treatment strategies include lifestyle changes, oral hypoglycemics, and in more severe cases, insulin therapy. Among the newer classes of antidiabetic drugs, DPP-4 inhibitors have gained attention for their efficacy and safety profile. One particularly promising drug in this class is Trelagliptin — a once-weekly oral DPP-4 inhibitor that offers patients more convenience and adherence with fewer doses.

What is Trelagliptin?

Trelagliptin succinate, marketed under the brand name Zafatek, is a dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Takeda Pharmaceutical Company in Japan. It is distinguished by its once-weekly dosing schedule — a stark contrast to most DPP-4 inhibitors that require once-daily administration.

It received approval in Japan in 2015, becoming the world's first once-weekly DPP-4 inhibitor, but it has not yet been widely approved in other countries.

The Science Behind DPP-4 Inhibitors

To understand the role of Trelagliptin, it's essential to first understand the DPP-4 mechanism:

The DPP-4 enzyme rapidly degrades incretin hormones such as GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide).

These incretins enhance insulin secretion and suppress glucagon release, thus lowering blood glucose levels.

By inhibiting DPP-4, drugs like Trelagliptin increase the half-life of GLP-1 and GIP, leading to better glucose regulation

Unique Advantages of Trelagliptin

1. Once-Weekly Dosing

The standout feature of Trelagliptin is its long half-life (about 5 days), allowing for once-weekly administration. This improves medication adherence, especially in patients with polypharmacy or difficulty following complex regimens.

2. Stable Glycemic Control

Clinical trials have shown that Trelagliptin provides stable reductions in HbA1c, fasting plasma glucose (FPG), and postprandial glucose levels, comparable to other daily DPP-4 inhibitors like sitagliptin or linagliptin.

3. Minimal Risk of Hypoglycemia

As with other DPP-4 inhibitors, Trelagliptin has a glucose-dependent mechanism, meaning it enhances insulin secretion only when blood sugar is elevated — reducing the risk of hypoglycemia.

4. Weight Neutrality

Trelagliptin is weight-neutral, an important advantage over other antidiabetic medications such as sulfonylureas or insulin, which are associated with weight gain.

Pharmacokinetics and Pharmacodynamics

Trelagliptin exhibits favorable pharmacokinetic properties:

Bioavailability: High oral bioavailability.

Half-life: Approximately 5 days, enabling once-weekly dosing.

Metabolism: Primarily via the liver with minimal renal excretion, making it potentially suitable for patients with mild to moderate renal impairment.

Selectivity: High selectivity for DPP-4 with minimal off-target effects.

Clinical Trials and Efficacy

1. Phase III Studies in Japan

A large multicenter, randomized, double-blind trial compared Trelagliptin (100 mg weekly) to Sitagliptin (50 mg daily).

After 24 weeks, both groups showed similar reductions in HbA1c (~ -0.7%).

Adverse events were mild and comparable between groups.

2. Add-on Therapy

Trelagliptin has been tested as an add-on therapy to metformin, sulfonylureas, and thiazolidinediones, showing consistent efficacy across various treatment backgrounds.

3. Real-World Evidence

Post-marketing surveillance in Japan continues to support the drug’s long-term safety and effectiveness, particularly among elderly patients.

Safety and Tolerability

Trelagliptin’s safety profile is consistent with other DPP-4 inhibitors:

Common side effects: Nasopharyngitis, headache, gastrointestinal discomfort.

Rare side effects: Pancreatitis, allergic reactions, skin disorders.

No significant cardiovascular concerns: Unlike some antidiabetic drugs, Trelagliptin does not increase the risk of heart failure or myocardial infarction.

Comparison with Other DPP-4 Inhibitors

Patient-Centric Benefits

Trelagliptin is particularly suited for:

Elderly patients: Who may struggle with daily medication schedules.

Busy individuals: Seeking simple treatment regimens.

Patients with polypharmacy: Reducing pill burden can improve adherence.

Mild renal impairment: As no significant dose adjustment may be needed.

Challenges and Limitations

Despite its promise, Trelagliptin faces several barriers:

1. Limited Global Approval

Currently, Trelagliptin is only approved in Japan. Regulatory hurdles and strategic decisions by the manufacturer have delayed its launch in other countries.

2. Lack of Cardiovascular Outcome Trials (CVOTs)

Unlike other DPP-4 inhibitors that have undergone large CVOTs (e.g., TECOS, SAVOR-TIMI), Trelagliptin lacks such large-scale data, limiting its acceptance in markets where such evidence is mandatory.

3. Market Competition

The rise of GLP-1 receptor agonists and SGLT2 inhibitors — both of which provide weight loss and cardio-renal benefits — have shifted the focus away from DPP-4 inhibitors in many treatment guidelines.

The Future of Trelagliptin

Given the increasing emphasis on patient adherence and personalized medicine, there is a niche for long-acting oral antidiabetic drugs. Trelagliptin’s once-weekly profile positions it uniquely, especially in regions with rising rates of T2DM and healthcare resource constraints.

Future directions may include:

Global clinical trials to seek approval outside Japan.

Fixed-dose combinations with other oral agents like metformin.

Cardiovascular safety studies to enhance clinician confidence.

Expert Opinions

Endocrinologists and diabetologists see potential in Trelagliptin, particularly for select patient populations. According to Dr. Hiroshi Maegawa, a prominent Japanese diabetes researcher:

> “Trelagliptin offers convenience and effective glycemic control. It’s a suitable option for patients seeking a low-burden regimen without compromising safety.”

Conclusion

Trelagliptin represents a significant innovation in the management of type 2 diabetes. Its once-weekly dosing improves adherence, its safety and tolerability are comparable to existing DPP-4 inhibitors, and its glycemic control is effective and stable.