In a new guideline issued today, the National institute for Health and Clinical Excellence (NICE) is recommending for the first time the consideration of DPP-4 (dipeptidyl peptidase-4) inhibitors (gliptins) such as vildagliptin or sitagliptin for selected type 2 diabetes patients who remain uncontrolled despite taking metformin monotherapy (their blood glucose remains greater than or equal to 6.5% HbA1c).
The guideline on newer agents for blood glucose control in type 2 diabetes recommends:
Adding a DDP-4 inhibitor as secondline therapy instead of a sulphonylurea in patients uncontrolled on metformin monotherapy if they are at significant risk of hypoglycaemia or its consequences, or if they do not tolerate a sulphonylurea (or it is contraindicated).
That a DPP-4 inhibitor may be preferable to a thiazolidinedione as second-line therapy for people in whom further weight gain would cause or exacerbate significant problems associated with a high body weight.
These recommendations are important for everyday clinical practice as in 2004 a significant number of people – up to 60% on metformin monotherapy continued to have uncontrolled diabetes despite treatment (may not maintain a target HbA1c below 7%). The NICE guideline target is 6.5%, therefore, the number of uncontrolled patients on metformin monotherapy could now be higher.
Dr Marc Evans said, "With this mandate, we can now help the many thousands of people who have uncontrolled type 2 diabetes on metformin monotherapy with effective treatments that may also help reduce the burden of undesirable therapy-related side effects, such as weight gain and hypoglycaemia."
Despite the risks, few patients with type 2 diabetes report hypoglycaemia to their doctor. In one study only 15% of type 2 diabetes patients who experienced a hypoglycaemic event reported the incident to their doctor at the next scheduled visit.
Around 90% of type 2 diabetes cases are attributed to weight gain. A 5 kg increase in bodyweight leads to a 29% increase in the risk of coronary heart disease.
An important consideration when choosing an add-on therapy to metformin will therefore be the potential for weight gain - an established side effect of thiazolidinediones and sulphonylureas.
It is important to note that compared to a thiazolidinedione or a sulphonylurea, gliptins deliver a comparable HbA1c reductions when added to metformin without additional weight gain.