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Linagliptin

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. Marketed combined with empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, as Glyxambi, the pairing brings together two antihyperglycaemic medicines with complementary mechanisms of action to improve glycaemic control in adults with type 2 diabetes. Glyxambi is indicated as an adjunct to diet and exercise to improve glycaemic control in these adults, according to its US prescribing information.

Glyxambi

Type 2 Diabetes Mellitus

10mg + 5mg

Developed to mitigate high blood sugar parameters to support cardiovascular wellness and target metabolic targets.

From$3.04/ tabletView

Jentadueto Xr

Type 2 Diabetes Mellitus

5mg + 1000mg

Developed to mitigate elevated blood glucose to support long-term metabolic health and target insulin receptor action.

From$1.90/ tabletView

Tradjenta

Type 2 Diabetes Mellitus

10mg

Developed to mitigate blood glucose parameters to support long-term metabolic health and target insulin secretion.

From$2.19/ tabletView

Jentadueto

Type 2 Diabetes Mellitus

2.5mg + 500mg

Indicated to manage glycaemic control in adults and developed to support blood glucose reduction in type 2 diabetes.

From$1.37/ tabletView

Key points

  • Linagliptin is a weak to moderate inhibitor of the CYP3A4 enzyme, though it does not inhibit or induce the other cytochrome P450 isozymes tested, including CYP1A2, 2C9, 2C19 and 2D6.
  • In linagliptin monotherapy trials, adverse reactions reported in at least 2% of patients and more often than with placebo were nasopharyngitis (7.0% of patients on linagliptin and 6.1% on placebo), diarrhoea (3.3% and 3.0%) and cough (2.1% and 1.4%).
  • Acute pancreatitis, including fatal cases, has been reported in patients treated with linagliptin, and postmarketing reports have continued to describe fatal pancreatitis in people taking it.
  • Postmarketing reports describe serious hypersensitivity reactions, including anaphylaxis, angioedema and exfoliative skin conditions, with onset mostly in the first three months after starting linagliptin.

How it works

Linagliptin blocks the DPP-4 enzyme that normally breaks down the incretin hormones GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), hormones released by the gut after eating. By inhibiting DPP-4, linagliptin raises the level of active incretin hormones in the circulation, which stimulates the release of insulin in a glucose-dependent manner and lowers glucagon.

Safety specific to linagliptin

Acute pancreatitis, including fatal cases, has been reported in patients treated with linagliptin. In the CARMELINA cardiovascular outcomes trial, two patients treated with linagliptin had acute pancreatitis with a fatal outcome, and postmarketing reports have continued to describe fatal pancreatitis in people taking the medicine.

Postmarketing use has also produced reports of serious hypersensitivity reactions in patients treated with linagliptin, including anaphylaxis, angioedema and exfoliative skin conditions. Onset occurred predominantly within the first three months of starting treatment, with some reports following the very first dose.

Severe and disabling joint pain (arthralgia) has been reported in patients taking linagliptin, in postmarketing use. Time to onset varied from one day to years after starting the medicine, and patients experienced relief of their symptoms once it was stopped.

Bullous pemphigoid, a blistering skin condition, was reported in 7 of the patients treated with linagliptin in the CARMELINA trial (0.2%), against none of the patients on placebo, and postmarketing cases requiring hospitalisation have also been described with DPP-4 inhibitor use. People who developed it typically recovered with topical or systemic immunosuppressive treatment and by stopping the DPP-4 inhibitor.

When to seek urgent care

Seek urgent medical attention for signs of a serious allergic reaction to linagliptin, including anaphylaxis, angioedema or exfoliative skin conditions. These reactions have been reported mostly within the first three months of starting the medicine, including after the first dose.

Further reading

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