Adult: Conventional tab: Linagliptin 2.5 mg and metformin 500 mg Linagliptin 2.5 mg and metformin 850 mg Linagliptin 2.5 mg and metformin 1,000 mg
As an adjunct to diet and exercise to improve glycaemic control: 1 tab bid. Individualise the dose according to patient's response, tolerability and current antidiabetic regimen. Max: 5 mg linagliptin/2,000 mg metformin daily.
Extended-release tab: Linagliptin 2.5 mg and metformin 1,000 mg Linagliptin 5 mg and metformin 1,000 mg
As an adjunct to diet and exercise to improve glycaemic control: Initially, 5 mg/1,000 mg once daily. Titrate and individualise the dose according to patient's response, tolerability and current antidiabetic regimen. Max: 5 mg linagliptin/2,000 mg metformin daily. Dosage and available fixed-dose combinations may vary between countries (refer to detailed product guidelines).
What are the brands available for Linagliptin + Metformin in Malaysia?
Patients taking concurrent insulin or insulin secretagogues (e.g. sulfonylurea): A lower dose of other concurrent antidiabetic agents may be required.
Renal Impairment
Severe (eGFR <30 mL/min/1.73 m2): Contraindicated.
Hepatic Impairment
Contraindicated.
Administration
Linagliptin + Metformin Should be taken with food. Linagliptin + Metformin hydrochloride Should be taken with food. ER Tab: Swallow whole & do not break/crush.
Contraindications
Acute or chronic metabolic acidosis (e.g. diabetic ketoacidosis, lactic acidosis), diabetic pre-coma, acute conditions that may alter renal function (e.g. dehydration, severe infections, shock), acute or chronic diseases that may cause tissue hypoxia (e.g. cardiac or respiratory failure, recent MI, sepsis), acute alcohol intoxication, alcoholism. Hepatic and severe renal impairment (eGFR <30 mL/min/1.73 m2). Concomitant intravascular administration of iodinated contrast agents.
Special Precautions
Patient with history of or risk factors for heart failure; history of pancreatitis; history of angioedema with another dipeptidyl peptidase-4 (DDP-4) inhibitor. Withhold treatment at the time of surgical procedures under general, spinal, or epidural anaesthesia; may restart treatment no earlier than 48 hours after surgery or resumption of oral nutrition and once renal function is stable. Not indicated for use in patients with type 1 diabetes mellitus. Mild to moderate renal impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Severe and disabling arthralgia, bullous pemphigoid, vitamin B12 deficiency (prolonged use), hypersensitivity reactions (e.g. anaphylaxis, angioedema, exfoliative skin conditions); hypoglycaemia (particularly when used concomitantly with insulin or insulin secretagogue). Gastrointestinal disorders: Abdominal pain, diarrhoea, nausea, vomiting, taste disturbance. Investigations: Increased lipase and amylase. Metabolism and nutrition disorders: Decreased appetite. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, cough. Skin and subcutaneous tissue disorders: Rash, pruritus. Potentially Fatal: Lactic acidosis, acute pancreatitis.
Monitor plasma glucose (frequency depends on individual treatment regimen, hypoglycaemia risk, and other patient-specific factors); haematologic parameters such as Hb/haematocrit, RBC indices (annually); renal function (before treatment initiation then at least every 3-6 months during therapy or annually); vitamin B12 level (every 1-2 years, particularly in predisposed patients); HbA1c (at least twice yearly for those who have stable glycaemic control and are meeting the treatment goals, quarterly for patients not meeting the treatment goals or with therapy changes). Assess for signs and symptoms of lactic acidosis, pancreatitis, heart failure, and development of skin erosions or blisters.
Overdosage
Symptoms: Metformin: Lactic acidosis. Management: Supportive treatment. May perform haemodialysis to remove lactate and metformin.
Drug Interactions
Increased risk of hypoglycaemia with insulin or insulin secretagogues (e.g. sulfonylurea). Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens or oral contraceptives, sympathomimetics, phenytoin, nicotinic acid, Ca channel blockers and isoniazid may produce hyperglycaemia, which may result in loss of glycaemic control.
Metformin: May increase the risk of lactic acidosis with topiramate or other carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, dichlorphenamide), NSAIDs (including COX-2 inhibitors, ACE inhibitors, angiotensin II receptor antagonists, diuretics [especially loop diuretics]). Enhanced gastrointestinal absorption and efficacy with organic cation transporters-1 (OCT1) inducers (e.g. rifampicin). Reduced efficacy with OCT1 inhibitors (e.g. verapamil). Decreased renal elimination resulting in increased plasma concentration with organic cation transporters-2 (OCT2) inhibitors (e.g. cimetidine, dolutegravir, isavuconazole, ranolazine, trimethoprim, vandetanib). Altered efficacy and renal elimination with OCT1 and OCT2 inhibitors (e.g. crizotinib, olaparib). Potentially Fatal: Metformin: May cause contrast-induced nephropathy leading to metformin accumulation and increased risk of lactic acidosis with intravascular iodinated contrast agents.
Food Interaction
Increased risk of lactic acidosis with alcohol.
Action
Description: Mechanism of Action: Linagliptin is an inhibitor of dipeptidylpeptidase-4 (DPP-4), an enzyme that inactivates incretin hormones. Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic β-cells in the presence of normal and elevated blood glucose levels. Additionally, GLP-1 lowers glucagon secretion from pancreatic α-cells, resulting in decreased hepatic glucose production. Linagliptin thereby prolongs active incretin levels in the bloodstream, stimulates insulin release in a glucose-dependent manner, and reduces glucagon levels in the circulation resulting in the improvement of glucose homeostasis.
Metformin is a biguanide antidiabetic agent. It reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, decreases intestinal absorption of glucose, and enhances insulin sensitivity by increasing peripheral uptake and utilisation of glucose. Onset: Metformin: Within days. Pharmacokinetics: Absorption: Linagliptin: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 30%. Time to peak plasma concentration: Approx 1.5 hours.
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Food reduces the extent and slightly delays the absorption. Absolute bioavailability: 50-60% (fasting). Time to peak plasma concentration: 2-3 hours (conventional form); 6-8 hours (extended-release tab). Distribution: Linagliptin: Extensively distributed to the tissues. Plasma protein binding: 70-80% (concentration-dependent).
Metformin: Partitions into erythrocytes; concentrates in liver, kidney, and gastrointestinal tract. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 654 ± 358 L. Metabolism: Linagliptin: Not extensively metabolised.
Metformin: Not metabolised. Excretion: Linagliptin: Via faeces (80% as unchanged drug); urine (5% as unchanged drug). Elimination half-life: Approx 11 hours; approx 200 hours (terminal).
Metformin: Via urine (90% as unchanged drug). Elimination half-life: 4-9 hours (plasma); approx 17.6 hours (blood).
Chemical Structure
Linagliptin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 10096344, Linagliptin. https://pubchem.ncbi.nlm.nih.gov/compound/Linagliptin. Accessed Oct. 23, 2023.
Metformin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4091, Metformin. https://pubchem.ncbi.nlm.nih.gov/compound/Metformin. Accessed Apr. 29, 2025.
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