Ten years of sitagliptin

  • Sitagliptin is an oral blood glucose lowering agent of the DPP-4 type, intended for use by patients with type 2 diabetes. Its registration has been extended from combination therapy with metformin or with pioglitazone to its use as a monotherapy if metformin is contraindicated. The drug was also authorised for combination therapy with sulfonylureas and/or insulin and as a triple therapy combining sitagliptin and metformin with pioglitazone, sulfonylureas or insulin.
  • Randomised studies assessing the reduction of the surrogate outcome measure of HbA1c value have found statistically significantly lower values with sitagliptin compared to placebo. However, the reduction was limited and its clinical relevance is unclear and unproven.
  • After its registration, the value of sitagliptin in terms of microvascular and macrovascular endpoints has not been proven in randomised studies. The only study of its cardiac outcomes, which was done 10 years after the product was registered, found that sitagliptin was not more effective than placebo.
  • After the registration of sitagliptin,  acute pancreatitis has been added to the product information as a serious side-effect with unknown frequency, although no evidence for this has so far been found in studies.
  • The number of users of sitagliptin is limited compared to that of the most commonly used oral blood glucose lowering agents, like metformin.
  • Sitagliptin is currently not recommended in the Dutch College of General Practitioners (NHG) guideline on type 2 diabetes mellitus, and the research findings discussed here do not give cause to reconsider this. 
  • Reviewing the balance of efficacy and side-effects of sitagliptin after 10 years results in the Ge-Bu drug rating for this agent being downgraded from ‘+/-’ (‘product of doubtful value or whose value can as yet not be adequately evaluated’), as it was rated 10 years ago, to ‘-’(‘product offering no added value’).

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  • mw drs M.A.E. Nieuwhof