Linagliptin Zentiva
Linagliptin 5 mg film-coated tablets — DPP-4 inhibitor for type 2 diabetes
Quick Facts About Linagliptin Zentiva
Key Takeaways
- Linagliptin Zentiva is a once-daily DPP-4 inhibitor tablet (5 mg) for adults with type 2 diabetes, taken with or without food
- No dose adjustment is needed for patients with kidney impairment (any stage) or liver impairment, making it unique among DPP-4 inhibitors
- It is weight-neutral and has a low risk of hypoglycaemia when used alone or with metformin
- It can be combined with metformin, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, or insulin for improved glycaemic control
- Patients should be aware of the rare risk of pancreatitis and bullous pemphigoid and seek medical attention if symptoms develop
What Is Linagliptin Zentiva and What Is It Used For?
Linagliptin Zentiva belongs to a class of medicines known as dipeptidyl peptidase-4 (DPP-4) inhibitors, sometimes called gliptins. These medications work by blocking the enzyme DPP-4, which normally breaks down incretin hormones (GLP-1 and GIP) in the body. When DPP-4 is inhibited, incretin hormone levels rise, stimulating the pancreas to produce more insulin and signalling the liver to produce less glucose — but only when blood sugar is elevated. This glucose-dependent mechanism means linagliptin carries a low risk of causing hypoglycaemia (dangerously low blood sugar) when used as monotherapy.
Linagliptin Zentiva is indicated for the treatment of type 2 diabetes mellitus in adults to improve glycaemic (blood sugar) control. It is approved by the European Medicines Agency (EMA) and is available as a generic version of the originator product. Type 2 diabetes is a chronic metabolic condition characterised by insulin resistance and progressive beta-cell dysfunction, leading to chronically elevated blood glucose levels. Without proper management, sustained hyperglycaemia can lead to serious complications affecting the heart, kidneys, eyes, nerves, and blood vessels.
The medication can be used in several treatment scenarios. It may be prescribed as monotherapy when diet and exercise alone provide inadequate glycaemic control, particularly in patients who cannot tolerate metformin or for whom metformin is contraindicated. More commonly, linagliptin is used as add-on combination therapy with other glucose-lowering agents. Approved combinations include linagliptin with metformin, linagliptin with a sulfonylurea (with or without metformin), linagliptin with a thiazolidinedione, linagliptin with an SGLT2 inhibitor (with or without metformin), and linagliptin with insulin (with or without metformin).
Clinical trials have demonstrated that linagliptin 5 mg once daily reduces HbA1c (a measure of average blood sugar over 2–3 months) by approximately 0.5–0.7 percentage points from baseline, depending on the combination used. Additionally, the large-scale cardiovascular outcomes trial CARMELINA (published in JAMA, 2019) demonstrated that linagliptin did not increase the risk of major adverse cardiovascular events (MACE) compared to placebo in patients with type 2 diabetes at high cardiovascular and renal risk, confirming its cardiovascular safety profile.
Importantly, linagliptin is not suitable for type 1 diabetes or for the treatment of diabetic ketoacidosis. It should not be used as a substitute for insulin in patients who require it. Linagliptin Zentiva is designed specifically for adults aged 18 years and over; its safety and efficacy in children and adolescents under 18 have not been established.
What Should You Know Before Taking Linagliptin Zentiva?
Contraindications
Linagliptin Zentiva must not be taken if you have a known hypersensitivity (allergy) to linagliptin or to any of the excipients listed in the product. Serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin conditions, have been reported in post-marketing surveillance. If you experience signs of a serious allergic reaction such as rash, hives, swelling of the face, lips, tongue or throat, or difficulty breathing or swallowing, you must stop taking the medicine and seek immediate medical attention.
Linagliptin Zentiva is also not indicated for type 1 diabetes mellitus or the treatment of diabetic ketoacidosis. Patients with these conditions require insulin therapy. If you have a history of severe or recurrent pancreatitis, your doctor should carefully evaluate the benefit-risk balance before prescribing this medicine.
Warnings and Precautions
Acute pancreatitis has been reported with DPP-4 inhibitors, including linagliptin. Inform your doctor immediately if you experience persistent, severe abdominal pain that may radiate to the back, with or without vomiting. If pancreatitis is confirmed, linagliptin must be discontinued permanently and should not be restarted.
Hypoglycaemia risk: Linagliptin alone has a low risk of hypoglycaemia. However, when combined with a sulfonylurea or insulin, the risk of hypoglycaemia increases significantly. Your doctor may need to reduce the dose of the sulfonylurea or insulin when adding linagliptin to your treatment regimen. Signs of hypoglycaemia include sweating, trembling, rapid heartbeat, hunger, blurred vision, difficulty concentrating, and feeling faint.
Bullous pemphigoid: Cases of bullous pemphigoid, a skin condition that causes large, fluid-filled blisters, have been reported with DPP-4 inhibitors. If blistering of the skin develops, linagliptin should be discontinued and medical advice sought. Hospitalisation may be required for treatment of bullous pemphigoid.
Heart failure: Clinical experience in patients with New York Heart Association (NYHA) functional class III–IV heart failure is limited. Caution is advised when using linagliptin in these patients. The CARMELINA trial found no increased risk of hospitalisation for heart failure with linagliptin compared to placebo, which is reassuring for the overall heart failure safety profile.
Pregnancy and Breastfeeding
There is limited data on the use of linagliptin in pregnant women. Animal studies have not shown direct harmful effects on reproductive development, but as a precautionary measure, linagliptin should not be used during pregnancy. If you are pregnant, think you may be pregnant, or are planning to have a baby, speak with your doctor before taking this medicine. Alternative diabetes treatments with more established safety profiles in pregnancy should be considered.
It is not known whether linagliptin passes into human breast milk. Animal studies have shown excretion of linagliptin in milk. A decision must be made whether to discontinue breastfeeding or discontinue linagliptin therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. Your doctor can help you weigh these considerations and choose the most appropriate course of action.
If you are a woman of childbearing age with type 2 diabetes, it is recommended that you discuss pregnancy planning and contraception with your doctor. Good glycaemic control before and during pregnancy is essential for the health of both mother and baby, and your treatment plan may need to be adjusted.
How Does Linagliptin Zentiva Interact with Other Drugs?
Linagliptin is primarily metabolised by CYP3A4 and is a substrate of P-glycoprotein (P-gp). However, it has a low potential for clinically relevant drug–drug interactions because it is used at a dose that is well above the minimum effective concentration, providing a significant margin. Additionally, linagliptin does not significantly inhibit or induce major CYP enzymes or drug transporters, meaning it is unlikely to affect the metabolism of other medicines you may be taking.
However, certain co-administered medicines can affect the exposure to linagliptin, and some combinations require additional monitoring or dose adjustments. The following table summarises key drug interactions to be aware of:
Major Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Rifampicin | Strong CYP3A4/P-gp inducer; reduces linagliptin exposure by approximately 40%, potentially reducing efficacy | Combination is not recommended. Consider an alternative diabetes medicine or an alternative to rifampicin |
| Sulfonylureas (e.g. glimepiride, glibenclamide) | Increased risk of hypoglycaemia due to additive glucose-lowering effect | A lower dose of the sulfonylurea may be required when combined with linagliptin. Monitor blood glucose regularly |
| Insulin | Increased risk of hypoglycaemia due to additive glucose-lowering effect | A lower dose of insulin may be required. Intensify blood glucose monitoring, especially when initiating combination |
Minor Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Ritonavir | Strong CYP3A4/P-gp inhibitor; increases linagliptin exposure by approximately 2-fold | No dose adjustment required; the increased exposure is not considered clinically relevant |
| Metformin | No pharmacokinetic interaction; both medicines can be used together | No dose adjustment of either medicine required. Common first-line combination |
| Pioglitazone | No clinically relevant pharmacokinetic interaction | No dose adjustment required. Can be used in combination |
| Digoxin | No clinically relevant interaction; steady-state digoxin levels unchanged | No dose adjustment required for either medicine |
| Warfarin | No clinically relevant interaction; INR not significantly affected | Standard INR monitoring should continue as usual |
Always inform your doctor or pharmacist about all medicines you are taking, including prescription medicines, over-the-counter medicines, herbal products, and dietary supplements. While linagliptin has a favourable interaction profile, a complete medication review ensures safe and effective treatment. This is particularly important if you are taking strong CYP3A4 inducers such as carbamazepine, phenobarbital, or phenytoin, as these may also reduce linagliptin exposure similar to rifampicin.
What Is the Correct Dosage of Linagliptin Zentiva?
Adults
Standard Adult Dose
The recommended dose is 5 mg linagliptin once daily. The tablet should be swallowed whole with a glass of water, at any time of day, with or without food. Try to take it at approximately the same time each day to help you remember. There is no need to titrate or adjust the dose over time — the 5 mg dose is the standard effective dose for all adult patients.
When linagliptin is used in combination with metformin, the dose of metformin should be maintained as prescribed. When added to a sulfonylurea or insulin, your doctor may reduce the dose of the sulfonylurea or insulin to minimise the risk of hypoglycaemia. Clinical studies show that the glucose-lowering effect of linagliptin is consistent regardless of age, body weight, sex, race, or baseline kidney function, so no dose individualisation is necessary.
Special Populations
| Patient Group | Recommended Dose | Notes |
|---|---|---|
| Elderly (≥65 years) | 5 mg once daily | No dose adjustment needed. Clinical experience in patients over 80 is limited |
| Renal impairment (mild to severe, including dialysis) | 5 mg once daily | No dose adjustment required at any stage of renal impairment, including end-stage renal disease requiring dialysis |
| Hepatic impairment | 5 mg once daily | No dose adjustment needed. Pharmacokinetic studies show no clinically relevant changes in exposure |
| Children and adolescents (<18 years) | Not recommended | Safety and efficacy have not been established in paediatric populations |
Missed Dose
If you forget to take your tablet, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take your next dose at the regular time. Do not take a double dose to make up for a forgotten tablet. If you are unsure what to do, contact your doctor or pharmacist for advice. Setting a daily reminder on your phone or placing the tablet package next to something you use every day (such as a toothbrush) can help establish a consistent routine.
Overdose
In clinical trials, single doses of up to 600 mg linagliptin (120 times the recommended dose) were well tolerated in healthy volunteers, with no clinically relevant adverse effects observed. There is no specific antidote for linagliptin overdose. In the event of an overdose, supportive care should be provided, including monitoring of blood glucose levels. Linagliptin is not meaningfully removed by haemodialysis due to its extensive protein binding. If you suspect an overdose, contact your local poison control centre or seek emergency medical attention immediately.
What Are the Side Effects of Linagliptin Zentiva?
Like all medicines, Linagliptin Zentiva can cause side effects, although not everybody gets them. Clinical trials involving over 8,000 patients treated with linagliptin provided comprehensive safety data, and the medicine has been generally well tolerated with a safety profile similar to placebo in many studies. The side effects are listed below by frequency category, based on clinical trial data and post-marketing surveillance.
The frequency categories are defined as follows: Very common affects more than 1 in 10 people; Common affects 1 in 10 to 1 in 100 people; Uncommon affects 1 in 100 to 1 in 1,000 people; Rare affects fewer than 1 in 1,000 people.
Very Common (>1/10)
Affects more than 1 in 10 people
- Hypoglycaemia (low blood sugar) — when used in combination with a sulfonylurea and metformin
Common (1/10 to 1/100)
Affects 1 in 10 to 1 in 100 people
- Nasopharyngitis (common cold symptoms: runny or stuffy nose, sore throat)
- Cough
- Hypoglycaemia — when used with insulin (with or without metformin)
- Increased lipase levels (detected in blood tests, usually without symptoms)
Uncommon (1/100 to 1/1,000)
Affects 1 in 100 to 1 in 1,000 people
- Pancreatitis (inflammation of the pancreas) — persistent, severe abdominal pain
- Hypersensitivity reactions (rash, urticaria, angioedema)
- Increased amylase levels (detected in blood tests)
Rare (<1/1,000)
Affects fewer than 1 in 1,000 people
- Bullous pemphigoid (large, fluid-filled blisters on the skin, typically in the folds of the skin or trunk)
- Anaphylaxis (severe life-threatening allergic reaction)
- Angioedema (swelling of the face, lips, tongue, and/or throat that can cause difficulty breathing or swallowing)
- Exfoliative skin conditions (severe peeling or blistering of the skin)
- Rhabdomyolysis (muscle breakdown — reported in post-marketing; causal relationship uncertain)
- Mouth ulceration and stomatitis
Stop taking Linagliptin Zentiva and contact your doctor or go to the nearest emergency department immediately if you experience: severe abdominal pain that does not go away (possible pancreatitis); swelling of face, lips, tongue or throat with difficulty breathing (possible angioedema/anaphylaxis); large blisters on the skin (possible bullous pemphigoid); or signs of a severe skin reaction. These are serious side effects that require urgent medical attention.
In the large-scale CARMELINA cardiovascular safety trial involving over 6,000 patients followed for a median of 2.2 years, the overall incidence of adverse events was similar between linagliptin and placebo groups. There was no increased risk of major cardiovascular events, heart failure hospitalisation, pancreatic cancer, or bone fractures. The CAROLINA trial, which compared linagliptin head-to-head with glimepiride (a sulfonylurea) in over 6,000 patients, confirmed that linagliptin caused significantly fewer hypoglycaemic episodes and less weight gain than glimepiride, while providing comparable cardiovascular safety.
If you experience any side effects, including any not listed above, talk to your doctor or pharmacist. You can also report side effects directly to your national pharmacovigilance authority to help monitor the ongoing safety of medicines.
How Should You Store Linagliptin Zentiva?
Proper storage of medicines is essential to ensure they remain effective and safe to use throughout their shelf life. Linagliptin Zentiva tablets should be stored under the following conditions:
- Temperature: Store below 30°C (86°F). No special temperature storage conditions are required under normal household conditions in most climates.
- Moisture protection: Store in the original blister packaging to protect from moisture. Do not transfer tablets to another container unless it provides equivalent moisture protection.
- Light: No special precautions for protection from light are required.
- Keep out of reach of children: Store the medicine in a safe place where children cannot see or reach it.
Do not use this medicine after the expiry date which is stated on the blister pack and outer carton after "EXP". The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.
If a tablet appears discoloured, damaged, or shows signs of deterioration, do not take it. Consult your pharmacist for a replacement. When travelling, keep the medicine in your carry-on luggage to avoid exposure to extreme temperatures in the cargo hold. In hot climates, be mindful of storing the medicine in vehicles where temperatures can rise significantly.
What Does Linagliptin Zentiva Contain?
Understanding what a medicine contains can be important, particularly for patients with known allergies or sensitivities to certain ingredients. Below is a complete breakdown of the contents of Linagliptin Zentiva 5 mg film-coated tablets:
Active substance: Each tablet contains 5 mg linagliptin.
Tablet core excipients:
- Mannitol (E421)
- Pregelatinised starch (maize)
- Maize starch
- Copovidone
- Magnesium stearate
Film coating:
- Hypromellose
- Titanium dioxide (E171)
- Talc
- Macrogol (polyethylene glycol 6000)
- Iron oxide red (E172)
Appearance: Linagliptin Zentiva 5 mg tablets are light pink, round, biconvex (curved on both sides) film-coated tablets. They are debossed with identification markings on one side. Each tablet is approximately 8 mm in diameter.
Pack sizes: The tablets are available in blister packs. Common pack sizes include 10, 14, 28, 30, 56, 60, 84, 90, 98, and 100 film-coated tablets, though not all pack sizes may be marketed in every country.
Linagliptin Zentiva does not contain lactose, gluten, or sucrose. It does contain mannitol (E421). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. Patients with known allergies to maize (corn) products should be aware that the tablet contains maize starch.
Frequently Asked Questions About Linagliptin Zentiva
Linagliptin Zentiva is used to treat type 2 diabetes mellitus in adults. It works by inhibiting the enzyme DPP-4, which helps increase insulin production and lower blood sugar levels in a glucose-dependent manner. It can be used alone when metformin is not tolerated, or more commonly as add-on therapy with metformin, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, or insulin. It is not suitable for type 1 diabetes or diabetic ketoacidosis.
Take one 5 mg tablet once daily, with or without food, at approximately the same time each day. Swallow the tablet whole with a glass of water. If you miss a dose, take it as soon as you remember. If it is close to your next scheduled dose, skip the missed dose. Never take a double dose. The 5 mg dose is the same for all adults, regardless of age, weight, or kidney function.
No. Linagliptin is considered weight-neutral, meaning it does not typically cause significant weight gain or weight loss. This is a notable advantage over some other diabetes medications such as sulfonylureas, thiazolidinediones, or insulin, which can be associated with weight gain. The CAROLINA trial confirmed minimal impact on body weight compared to glimepiride over several years of treatment.
No. Linagliptin Zentiva does not require dose adjustment for patients with any degree of renal impairment, including those on dialysis. This is because linagliptin is primarily eliminated through the bile and gut rather than the kidneys (less than 5% is excreted renally). This makes it unique among DPP-4 inhibitors and a particularly convenient option for patients with chronic kidney disease and type 2 diabetes.
Yes. Linagliptin combined with metformin is one of the most common and well-studied treatment combinations. No dose adjustment of either medicine is needed. This combination is recommended by major guidelines (ADA/EASD) as an appropriate dual therapy option for patients who are not achieving adequate glycaemic control with metformin alone. Fixed-dose combination tablets containing both linagliptin and metformin are also available in many countries.
Pancreatitis has been reported as an uncommon side effect in post-marketing surveillance of DPP-4 inhibitors, including linagliptin. However, large-scale clinical trials (CARMELINA and CAROLINA) did not show a significantly increased risk of pancreatitis with linagliptin compared to placebo or glimepiride. Nevertheless, patients should be informed about the symptoms of acute pancreatitis (persistent, severe abdominal pain, often radiating to the back) and advised to seek immediate medical attention if these occur.
References
All medical information is based on peer-reviewed research, international guidelines, and regulatory agency assessments. This content is independent and receives no commercial funding.
- European Medicines Agency (EMA). Linagliptin — Summary of Product Characteristics (SmPC). Last updated 2024. Available at: www.ema.europa.eu
- Rosenstock J, Perkovic V, Johansen OE, et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019;321(1):69–79. doi:10.1001/jama.2018.18269
- Rosenstock J, Kahn SE, Johansen OE, et al. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019;322(12):1155–1166. doi:10.1001/jama.2019.13772
- American Diabetes Association. Standards of Care in Diabetes — 2024. Diabetes Care. 2024;47(Supplement_1):S1–S321.
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- National Institute for Health and Care Excellence (NICE). Type 2 diabetes in adults: management (NG28). Last updated 2022. Available at: www.nice.org.uk/guidance/ng28
- U.S. Food and Drug Administration (FDA). Tradjenta (linagliptin) — Prescribing Information. Last revised 2023. Available at: www.fda.gov
- Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011;13(1):7–18. doi:10.1111/j.1463-1326.2010.01306.x
- Groop PH, Cooper ME, Perkovic V, et al. Linagliptin and Its Effects on Hyperglycaemia and Albuminuria in Patients With Type 2 Diabetes and Renal Dysfunction: the Randomized MARLINA-T2D Trial. Diabetes Obes Metab. 2017;19(11):1610–1619. doi:10.1111/dom.13041
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