Diabete: dipeptyl peptidase-4 inhibitors and sulphonylureas, an association with potential risks


In the article published in the BMJ of may 2016, Francesco Salvo, researcher in the team “Pharmacoepidemiology and population impact of drugs” in the Bordeaux population health research center U1219, recalls the importance of compliance with recommendations regarding dipeptyl peptidase-4 inhibitors (DPP-4) and sulphonylureas when these drugs are associated in diabetics patients,. This article allows an assessment of the risk of hypoglycemia for this drug association.

As a reminder, Type 2 Diabetes Mellitus is characterized by a loss of control in blood glucose level. This and the associated elevated glucose concentrations (hyperglycemia) can lead to severe health issues (particularly cardiovascular problems).
Type 2 Diabetes Mellitus management implies first to adopt a healthier way of life, second to resort to different drug treatments. The objective of these is to achieve glucose level control and reduce hyperglycemia. However, an over-control of the blood sugar, or an inadequate treatment may conversely induce hypoglycemia (too low blood glucose level).

Used to control the blood sugar of diabetes of type 2, DPP-4 inhibitors are mostly prescribed in association to others glucose lowering therapies, as sulphonylureas. This association increases the glycemic control; drug instructions inform that it can induce hypoglycemia. The magnitude of the increase in the risk of hypoglycemia that this association conveys was unknown till now.

With a systematic review and a meta-analysis of 10 studies regarding this association (which included 6546 participants), Francesco Salvo confirms that the association between those two types of drugs increases the risk of hypoglycemia, and evaluate this increase to reach around 50%. In other words, for every ten patients treated with sulphonylureas, adding DPP-4 inhibitors would be responsible for one supplementary case of hypoglycemia.
Those results put the light on the requirement to follow the instructions about sulphonylureas prescriptions when they are associated with DPP-4 inhibitors.
Francesco Salvo explains “those instructions regarding prescriptions are of common sense, even their effectiveness in the limitation of the risk of hypoglycemia still needs to be confirmed. Further investigations are needed to improve the safe use of medicines in Type 2 Diabetes Mellitus”. 


Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ 2016; 353