Hope in a Weekly Pill: A Doctor’s Reflection

The life of a doctor on a 24‑hour shift is like being caught in a storm. My duty starts at 9 a.m. and ends at 9 a.m. the next day. There’s barely a quiet moment. It’s a continuous loop of emergencies, decisions, and caring for people on the edge. By 5:30 p.m., even though the night lies ahead, the tiredness sinks deep into the bones. There’s no real break — not even for 30 minutes. This life, though meaningful, slowly chips away at health, sleep, and sometimes, the spirit.

In the emergency room, we often see patients with longstanding diabetes. Many have struggled for more than a decade. They are tired. Tired of taking pills — morning, noon, and night. They say it out loud: “Pills, pills, and more pills!” This fatigue leads to missed doses, rising sugar levels, and eventual organ damage—a painful cycle we see too often.

But even in this chaos, there's a quiet thread among us—shared knowledge. It’s not formal. It’s just someone sending a message, a link, a photo on WhatsApp, hoping to keep colleagues informed.

Yesterday, in a rare moment of pause, I checked my phone. A senior had sent a picture of a new medicine — Trelaglip. The words jumped out: “Once Weekly Oral DPP‑4i.” My heart skipped a beat. Could this be real?

I read the message: “Same day, every week. Trelaglip tablets.” That was it. A once-weekly oral medicine for type 2 diabetes. No more three-times-a-day routine. One tablet a week. Like Vitamin D. Simple. Manageable. Revolutionary.

If it works as promised, it could change everything. Patients might finally stick to treatment. That means better sugar control, fewer complications, and possibly, a better life. We’ve had weekly injections before. But a pill? That’s far more acceptable.

Of course, cost remains a question. But if the drug is effective, prices may fall. It could reach many, not just a few. For public health, it could be a game‑changer in our fight against diabetes.

It’s strange—how during a hectic shift, a colleague’s simple message can feel like a small light in the dark. These moments remind me why we keep going, even when exhausted. We’re all striving to improve patient lives.

Sometimes, hope arrives not in big discoveries, but in a small tablet taken once a week — and in a brief moment of shared belief.

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Once‑Weekly Oral Antidiabetic Therapy: A Public Health Perspective for India

Introduction

The rise of once‑weekly oral antidiabetic agents, such as Trelagliptin (a DPP‑4 inhibitor), could represent a breakthrough in managing type 2 diabetes mellitus (T2DM). In India, where diabetes prevalence is escalating, this innovation may reduce long‑term complications and improve adherence.

The Public Health Burden

Diabetes is a chronic disease with serious complications affecting both individuals and health systems:

• Microvascular: Retinopathy, nephropathy, neuropathy.
• Macrovascular: Heart attack, stroke, peripheral artery disease.
• Infections: Increased susceptibility due to reduced immunity.
• Quality of Life: Chronic disability and loss of productivity.

These complications heavily burden India’s healthcare resources and economy due to loss of productive life‑years.

The Role of Once‑Weekly Therapy

1. Medication Adherence

• Pill Fatigue: Reducing dose frequency simplifies treatment.
• Compliance: Less frequent dosing supports more consistent use and delayed progression.

2. Complication Reduction

• Microvascular: Better control reduces risks of blindness, dialysis, amputations.
• Cardiovascular: Stable glucose lowers heart attack and stroke incidence.
• Healthcare Demand: Fewer complications reduce hospital and specialist burden.

3. Quality of Life

• Self‑Confidence: Simpler regimens boost patient empowerment.
• Mental Health: Reducing daily reminders of illness eases stress.
• Productivity: Healthier patients support economic activity and relieve caregiver strain.

Challenges for Integration

• Cost‑effectiveness: Sustainable pricing and generics/essential medicine inclusion are needed.
• Rural Accessibility: It must reach primary health centers and NCD programs.
• Provider Training: Community doctors and health workers need education and support.

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Trelagliptin: Pharmacology and Clinical Profile

Introduction

Trelagliptin is a once‑weekly oral DPP‑4 inhibitor approved in Japan (March 2015) and India (December 2024) for T2DM management. It enhances incretin activity to improve glycemia with low hypoglycemia risk.

Mechanism of Action

• Inhibits DPP‑4, preserving GLP‑1 and GIP to enhance glucose‑dependent insulin and suppress glucagon.
• Slows gastric emptying; may support β‑cell health.
• High specificity (IC₅₀ ≈1.3–5.4 nmol/L).

Pharmacokinetics

• Oral bioavailability high; peak levels ~1–1.5 h post‑dose.
• Long elimination half‑life (38–54 h) supports once‑weekly dosing.
• Mainly renally excreted; minimal hepatic metabolism.

Pharmacodynamics

• Sustains ~70–80% DPP‑4 inhibition for a week.
• Phase 2/3 trials show HbA₁c reductions of ~0.5–1.0%.
• Weight‑neutral, low hypoglycemia risk when used alone.

Clinical Efficacy & Safety

• Monotherapy: dose‑dependent HbA₁c reduction similar to daily DPP‑4 inhibitors.
• Phase 3 trials show non‑inferiority versus alogliptin; good tolerability.
• Add‑on to insulin: ~0.63% greater HbA₁c reduction without severe hypoglycemia.
• Pilot studies: increased adiponectin; no endothelial compromise.
• Side effects: mild nasopharyngitis, headache, upper respiratory symptoms.

Clinical Implications

• Once‑weekly dosing boosts adherence, especially in low‑resource areas.
• Safe for diverse populations due to weight neutrality and low hypoglycemia risk.
• Effective as adjunct therapy with insulin.

Precautions & Dosing

• No dose adjustment in mild/moderate hepatic impairment.
• Renal impairment: dose reductions per eGFR recommendations.
• Use caution with insulin or sulfonylureas to avoid hypoglycemia.

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Safety Profile and Complications of Trelagliptin

Introduction

Trelagliptin is generally well tolerated, but distinguishing common side effects from rare serious complications is essential.

1. Hypoglycemia

• Monotherapy: low risk due to glucose‑dependent mechanism.
• Combined therapy: risk increases with sulfonylureas or insulin; adjust doses accordingly.

2. Pancreatitis

• Meta‑analyses show slight increase in acute pancreatitis risk (OR ~1.7).
• Rare cases (~0.3%) in clinical trials.
• Discontinue drug if pancreatitis suspected.

3. Bullous Pemphigoid

• Possible 2–4× increased risk, particularly in people >70 years.
• Discontinue if suspected; refer to dermatology.

4. Arthralgia

• Severe joint pain reported; typically resolves after stopping drug.

5. Hypersensitivity

• Rare angioedema, urticaria, anaphylaxis, especially in first 3 months.
• Discontinue immediately; manage supportively.

6. Heart Failure

• Saxagliptin and alogliptin showed heart failure risk, but no strong signal for Trelagliptin.
• Monitor in heart disease patients.

Other Observations

• Renal impairment: no major issues, but dose adjustments may be needed.
• Gallbladder events: slightly increased in meta‑analyses.

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Summary & Abbreviations

Summary: Trelagliptin is a once‑weekly oral DPP‑4 inhibitor offering simplified therapy, sustained glycemic control, and strong safety. It reduces pill burden, enhances adherence, and lowers complication risk. Rare but serious effects—pancreatitis, arthralgia, bullous pemphigoid, and hypersensitivity—require vigilance. While care is needed when combined with insulin or sulfonylureas or in comorbid conditions, the drug’s convenience and tolerability make it a promising option in diabetes management and public health.

Abbreviations:
DPP‑4 = dipeptidyl peptidase‑4 | GLP‑1 = glucagon‑like peptide‑1 | GIP = glucose‑dependent insulinotropic polypeptide | T2DM = type 2 diabetes mellitus | HbA_1c = glycated hemoglobin | eGFR = estimated glomerular filtration rate.

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