Linagliptin-Metformin Extended-Release Tablets (I) — a combination antidiabetic formulation manufactured by Hubei Guangchen Pharmaceutical Co., Ltd.

Linagliptin and Metformin Extended-Release Tablets (I)

— A compound hypoglycemic preparation manufactured by Hubei Guangchen Pharmaceutical Co., Ltd.

Product Overview

Linagliptin/metformin extended-release tablets (I), marketed under the brand name LedaTang®, is a combination antidiabetic formulation manufactured by Hubei Guangchen Pharmaceutical Co., Ltd., which also serves as the marketing authorization holder. It is the first extended-release formulation of its kind approved for marketing in China. This product combines the DPP‑4 inhibitor linagliptin with the biguanide drug metformin hydrochloride and, when used in conjunction with dietary management and exercise, is indicated for adult patients with type 2 diabetes who are suitable candidates for treatment with both linagliptin and metformin, to improve glycemic control.

Basic Information

Generic name	Linagliptin and Metformin Extended-Release Tablets (I)
Product Name	Leda Tang®
English name	Linagliptin and Metformin Hydrochloride Sustained-release Tablets（Ⅰ）
Hanyu Pinyin	Ligelieting Erjiashuanggua Huanshipian (I)
Drug type	Compound hypoglycemic preparation (prescription drug)
Specifications	Each tablet contains 5 mg of linagliptin and 1,000 mg of metformin hydrochloride.
Approval Number	National Drug Approval Number H20255813
Implementation Standard	National Medical Products Administration Drug Registration Standard YBH27042025
Marketing Authorization Holder	Hubei Guangchen Pharmaceutical Co., Ltd.
Manufacturing enterprise	Hubei Guangchen Pharmaceutical Co., Ltd.
Approval Date	October 28, 2025

Ingredients

This product is a combination formulation, with active ingredients of linagliptin and metformin hydrochloride.

Chemical name of linagliptin: 8-[（3R）-3-amino-1-piperidinyl]-7-（2-butyne-1-yl）-3,7-dihydro-3-methyl-1-[（4-methyl-2-quinazolinyl）methyl]-1H-purine-2,6-dione.

Chemical structural formula:

Molecular formula: C ₂₅ H ₂₈ N ₈ O ₂

Molecular weight: 472.54

Chemical name of metformin hydrochloride: 1,1-dimethylbiguanide hydrochloride.

Chemical structural formula:

Molecular formula: C ₄ H ₁₁ N ₅ • HCl

Molecular weight: 165.63

Excipients: hydroxypropyl methylcellulose, arginine, polyethylene glycol 6000, polyoxyethylene, magnesium stearate, talc, and a film-coating premix (enteric‑soluble).

Characteristics

This product is a off-white, oval-shaped, biconvex film-coated tablet; the core appears white after removal of the coating.

Indications

This product, in combination with dietary management and exercise, is indicated for adult patients with type 2 diabetes who are suitable for treatment with linagliptin and metformin, to improve glycemic control.

Specifications

Each tablet contains 5 mg of linagliptin and 1,000 mg of metformin hydrochloride.

Category of Action

A combination antidiabetic drug consisting of a dipeptidyl peptidase‑4 (DPP‑4) inhibitor and a biguanide.

Usage and Dosage

The dosage of this product should be individualized based on efficacy and tolerability and must not exceed the maximum recommended daily dose of 5 mg linagliptin/2,000 mg metformin hydrochloride. This product should be taken once daily, one tablet each time, with food. The dose should be titrated gradually to minimize gastrointestinal adverse events associated with metformin.

Recommended starting dose

● For patients already receiving metformin, the initial dose is 5 mg of linagliptin plus their current dose of metformin hydrochloride, administered once daily with meals.

● Patients already receiving linagliptin and metformin, or linagliptin/metformin tablets, may switch to 5 mg of linagliptin plus their current dose of metformin hydrochloride, taken once daily with food.

● This product should be swallowed whole; do not split, crush, dissolve, or chew it. (Each tablet contains 5 mg of linagliptin and 1,000 mg of metformin hydrochloride; it is not intended for other patients who require dose adjustments.)

Recommended dosage for patients with renal impairment

Renal function should be assessed prior to initiating treatment with this product and monitored periodically thereafter. This product is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m². If the patient’s eGFR subsequently declines to below 45 mL/min/1.73 m², discontinue this product.

Discontinue medication during contrast agent examination.

Intravascular injection of iodinated contrast agents may lead to contrast‑induced nephropathy, which can result in metformin accumulation and an increased risk of lactic acidosis. Therefore, patients scheduled for such procedures must discontinue this product prior to or during the examination. Reassess eGFR at least 48 hours after completion of the imaging study; if renal function remains stable, resume treatment with this product.

Adverse reaction

The following serious adverse reactions have been reported: lactic acidosis; pancreatitis; hypoglycemia when used in combination with insulin and insulin secretagogues; hypersensitivity reactions; vitamin B12 deficiency; severe and disabling arthralgia; bullous pemphigoid; and heart failure.

In clinical trials, among patients receiving linagliptin plus metformin, adverse events occurring in ≥5% of patients (n=875) and more frequently than with placebo plus metformin included nasopharyngitis (5.7% vs 4.3%), among others. Other adverse reactions reported in clinical studies included hypersensitivity reactions (such as urticaria, angioedema, or bronchial hyperreactivity), cough, decreased appetite, nausea, vomiting, pruritus, and pancreatitis.

Linagliptin: Adverse reactions more common than with placebo in ≥2% of patients included nasopharyngitis (7.0% vs 6.1%), diarrhea (3.3% vs 3.0%), and cough (2.1% vs 1.4%). Metformin: The most frequently reported adverse reactions at initiation (occurring in >5% of patients) were diarrhea, nausea/vomiting, flatulence, abdominal discomfort, dyspepsia, fatigue, and headache.

Post‑marketing adverse reactions: acute pancreatitis (including fatal cases), oral ulcers, and stomatitis; hypersensitivity reactions (including anaphylaxis, angioedema, and exfoliative skin disorders); rhabdomyolysis, severe and disabling arthralgia; bullous pemphigoid and rash; cholestatic, hepatocellular, and mixed hepatic injury.

Taboo

This product is contraindicated in patients with the following conditions:

● Severe renal impairment (eGFR less than 45 mL/min/1.73 m²);

● Acute or chronic metabolic acidosis, including diabetic ketoacidosis;

● Acute conditions that may impair renal function, such as dehydration, severe infection, and shock;

● Conditions that can cause tissue hypoxia (particularly acute conditions or exacerbations of chronic diseases), such as decompensated heart failure, respiratory failure, recent myocardial infarction, and shock;

● Severe infections and trauma, major surgical procedures, and clinical conditions such as hypotension and hypoxia;

● Prodromal phase of diabetic coma;

● Hepatic insufficiency, acute alcohol intoxication, and chronic alcohol abuse;

● Individuals with untreated vitamin B12 and folate deficiencies;

● Individuals with hypersensitivity to linagliptin, metformin, or any of the excipients in this product (e.g., those who have experienced immediate-type allergic reactions, angioedema, exfoliative skin disorders, urticaria, or bronchial hyperreactivity).

Precautions

1. Lactic Acidosis: Post‑marketing reports have documented cases of metformin‑associated lactic acidosis, including fatal instances, with insidious onset and nonspecific symptoms such as malaise, myalgia, abdominal pain, respiratory distress, or somnolence. If metformin‑associated lactic acidosis is suspected, discontinue this product immediately and initiate standard supportive care in a hospital setting; prompt initiation of hemodialysis is recommended.

2. Pancreatitis: Cases of acute pancreatitis, including fatal cases, have been reported in patients receiving linagliptin. If pancreatitis is suspected, this product should be discontinued immediately and appropriate management initiated.

3. Heart Failure: Patients at risk of heart failure should have the risks and benefits of this product carefully weighed prior to initiating treatment, and their clinical signs and symptoms of heart failure should be monitored throughout therapy. If heart failure develops, it should be evaluated and managed in accordance with current standard-of-care guidelines, and discontinuation of this product should be considered.

4. Hypersensitivity Reactions: Serious hypersensitivity reactions, including immediate-type allergic reactions, angioedema, and exfoliative skin disorders, have been reported in patients receiving linagliptin, most often within the first 3 months of treatment. If a severe hypersensitivity reaction is suspected, discontinue this product and initiate alternative diabetes therapy.

5. Vitamin B12 levels: Approximately 7% of patients taking metformin experience a decline in serum vitamin B12 levels from normal to below the normal range. It is recommended that patients on this medication undergo annual hematologic monitoring, with close observation and management of any clinically significant abnormalities.

6. Severe, disabling joint pain: Post‑marketing reports have documented severe, disabling joint pain associated with DPP‑4 inhibitors; discontinuation of the drug should be considered when appropriate.

7. Bullous pemphigoid: If bullous pemphigoid is suspected, discontinue this product and consider referring the patient to a dermatologist for diagnosis and appropriate treatment.

8. Hypoglycemia: When used in combination with insulin and/or insulin secretagogues, it may be necessary to reduce the dose of the insulin secretagogue or insulin to lower the risk of hypoglycemia.

9. During medication, excessive alcohol consumption should be avoided; in cases of surgery or other procedures, hypoxia, or hepatic impairment, dosage adjustments should be made as specified in the product labeling.

Medication for Special Populations

Medication Use in Pregnant and Breastfeeding Women

Pregnancy: Metformin is not recommended for patients who are planning to become pregnant or who are already pregnant; insulin may be used to maintain blood glucose levels as close to normal as possible, thereby reducing the risk of fetal malformations. Data on the use of this product and linagliptin in pregnant women are limited.

Lactation: Metformin is excreted in breast milk; breastfeeding is not recommended during metformin therapy.

Pediatric Medication

The safety and efficacy of this product in pediatric patients under 18 years of age have not been established.

Medication for the Elderly

Linagliptin is minimally excreted by the kidneys, whereas metformin is primarily eliminated via renal excretion. Given that renal function declines with age, this product should be used with caution, and elderly patients should undergo more frequent monitoring of renal function.

Drug interactions

Concomitant use of metformin with carbonic anhydrase inhibitors (such as topiramate and zonisamide), drugs that may reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine), and alcohol may increase the risk of lactic acidosis; benefits and risks should be carefully weighed, and monitoring should be intensified.

With linagliptin: Strong P-glycoprotein inducers or CYP3A4 inducers (such as rifampicin) may reduce linagliptin exposure. This product is a fixed-dose combination; if necessary, an alternative regimen without linagliptin is recommended. When used in combination with insulin secretagogues or insulin, dose reduction may be required to lower the risk of hypoglycemia.

Drug overdose

In the event of an overdose with this product, contact a poison control center. Hemodialysis or peritoneal dialysis is unlikely to remove linagliptin; however, hemodialysis may be effective in removing accumulated metformin.

Pharmacology, Toxicology, and Pharmacokinetics

Pharmacological effects: Linagliptin is a DPP‑4 inhibitor that increases the plasma concentrations of active incretin hormones, thereby stimulating insulin secretion in a glucose‑dependent manner and reducing circulating glucagon levels. Metformin hydrochloride is a biguanide antidiabetic agent that decreases hepatic gluconeogenesis, inhibits intestinal glucose absorption, and enhances peripheral glucose uptake and utilization, thus improving insulin sensitivity.

Toxicology Studies: Detailed results of genotoxicity, reproductive toxicity, and carcinogenicity studies for linagliptin and metformin hydrochloride are provided in the product labeling.

Pharmacokinetics: Compared with fasting conditions, administration of this product after a meal results in an approximately 54%–71% increase in the total exposure (AUC0–tz) of metformin, an approximately 11% increase in Cmax, and a prolongation of Tmax by about 3 hours; the total exposure to linagliptin decreases by approximately 7%–22%, which is not clinically relevant. For further details, please refer to the product’s package insert.

Storage, Packaging, and Shelf Life

● Storage: Keep sealed and store at a temperature not exceeding 25°C. Keep this product out of reach of children.

● Packaging: Oral solid dosage form in high-density polyethylene bottles, with silica gel desiccant packaged in solid pharmaceutical paper bags.

10 tablets/14 tablets/20 tablets per bottle.

● Shelf life: 24 months.

● Applicable Standard: Drug Registration Standard of the National Medical Products Administration, YBH27042025.

● Approval Number: National Drug Approval No. H20255813.