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How to use DPP4 inhibitors (gliptins) in clinical practice

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

In NICE guidance gliptins are a treatment option (1,2) in both possible treatment arms (metformin tolerant or metformin intolerant) (2):

If metformin tolerant then (2):

  • metformin is first line therapy and titrated up to usual maximum dose of 1g bd

  • a gliptin is an option for first intensification of therapy if, despite treatment with metformin, the HbA1c is > 58 (7.5%)

  • if a gliptin has not been used in the first intensification of therapy then it is an option for the second intensification
    • if HbA1c rises to 58 mmol/mol (7.5%)
      • metformin, a DPP-4 inhibitor (gliptin), and an sulphonyluria (SU)

If metformin intolerant then (2):

  • a gliptin is an option for first line therapy as is glitazone therapy or therapy with a sulphonylurea or an SGLT 2 inhibitor

  • pioglitazone is an option for dual therapy as first intensification of therapy if after initial therapy the HbA1c is > 58 (7.5%)
    • DPP-4i and pioglitazone
    • DPP-4i and an SU

For detailed and up to date information then it is advised consult the respective Summary of Product Characteristics (SPC) before prescribing a particular gliptin.

For detailed guidance then consult the full guideline (2).

Notes:

  • it was noted that gliptins are useful if (1)
    • the person is at significant risk of hypoglycaemia or its consequences
      • people who are risk in this category include older people and people in certain jobs [e.g. those working at heights or with heavy machinery] or people in certain social circumstances [e.g. if a person lives alone])

  • for the treatment of diabetes, the recommended doses of gliptins in the UK are:
    • alogliptin: 25 mg once daily
    • linagliptin: 5 mg once daily
    • saxagliptin: 5 mg once daily
    • sitagliptin: 100 mg once daily
    • vildagliptin: 50 mg twice daily

  • in people with renal impairment (3,4)
    • because most DPP-4 inhibitors are eliminated from the body by renal pathways, dose adjustment is required for patients with moderate or severe renal impairment when treated with alogliptin, sitagliptin, saxagliptin, or vildagliptin
    • linagliptin is primarily cleared by nonrenal mechanisms and therefore does not require dosage adjustment in patients with renal impairment (4)

  • if a gliptin is used in combination with an SU, a lower dose of the SU may be required to reduce the risk of hypoglycaemia
    • if vildagliptin is used in combination with an SU, then the recommended dose is 50 mg once daily, in the morning

  • summary of adverse effects associated with gliptin therapy (3,4)
    • generally have a good safety profile and are well tolerated, with a low risk of hypoglycemia (except when used in combination with insulin or insulin secretagogues)
    • gastrointestinal disturbances are common
    • nasopharyngitis may occur
    • serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin reactions, have been reported
    • musculoskeletal and connective tissue disorders (including back pain, arthralgia, myalgia, and arthropathy) may occur
    • there have been reports of acute pancreatitis in patients treated with DPP-4 inhibitors
      • prompt discontinuation of DPP-4 inhibitor treatment is recommended if pancreatitis is suspected (4)

  • DPP4-inhibitor or thiazolidinedione (1)
    • when would a glitazone be the preferred option?
      • thiazolidinedione (pioglitazone) may be preferable to a DPP-4 inhibitor if:
        • the person has marked insulin insensitivity, or
        • DPP-4 inhibitor is contraindicated, or
        • the person has previously had a poor response to, or did not tolerate, a DPP-4 inhibitor
    • when would the use of a DPP4-inhibitor be the preferred option?
      • a DPP-4 inhibitor may be preferable to a thiazolidinedione (pioglitazone) if:
        • weight gain related problem
          • further weight gain would cause or exacerbate significant problems associated with a high body weight, or
        • glitazones are contraindicated, or
        • patient has a previous poor response to, or did not tolerate, a glitazone
    • there may be some people for whom either a thiazolidinedione (pioglitazone) or a DPP-4 inhibitor may be suitable and, in this case, the choice of treatment should be based on patient preference

Reference:


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