- Linagliptin is the fourth gliptin available in the market. Its use has been approved for the treatment of type 2 diabetes mellitus as monotherapy when metformin is anappropriate due to intolerance or is contraindicated due to renal impairment, as a dual therapy in combination with metformin, as a triple therapy in combination with metformin and a sulphonylurea, and in association with insulin with or without metformin.
It has not been approved as a dual therapy in combination with sulphonylureas, with pioglitazone, nor as an initial combination therapy.
- In those cases when non-pharmacological measures do not provide adequate glycaemic control, clinical practice guidelines recommend the use of metformin monotherapy as first choice, and the use of a sulphonylurea as the alternative choice in patients with intolerance or contraindications to metformin. When monotherapy, with an optimal dose and proper adherence to treatment, is not sufficient, the combination therapy of metformin and a sulphonylurea is recommended. Gliptins may be considered as a dual combination therapy, as an alternative in cases of contraindication or intolerance to metformin or to sulphonylureas, or else as a triple combination with them.
- Efficacy of linagliptin has been assessed in randomised controlled clinical trials using the reduction in HbA1c (glycated hemoglobin) as the primary outcome variable. There are no studies available assessing its impact on morbidity and mortality.
- Compared to placebo, in both monotherapy and combination therapy (dual and triple), linagliptin has shown a reduction in HbA1c of limited magnitude (0.6%), lower than that observed with metformin, sulphonylureas and pioglitazone and similar to that of other gliptins.
- The only comparative study available showed that the combination of linagliptin + metformin was statistically inferior to glimepiride + metformin, despite meeting the pre-defined non-inferiority criterion.
- It does not require dose adjustment in renal impairment. Its long-term safety profile needs to be established with regards to the effects from the inhibition of the DPP-4 (Dipeptidyl peptidase 4) enzyme, related to the immune system (infections, hypersensitivity reactions, skin disorders, etc.), the chance of developing pancreatitis, as well as its cardiovascular safety.
- Evidence shows lower efficacy for linagliptin than for metformin and sulphonylureas and there is no evidence offering significant advantages over other gliptins. Therefore, linagliptin means no innovation in the therapeutics of type 2 diabetes mellitus.