english.prescrire.org > Spotlight > Archives : 2011 > Saxagliptin: no more effective than other gliptins, but a high potential for drug interactions

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Saxagliptin: no more effective than other gliptins, but a high potential for drug interactions

FEATURED REVIEW In patients with type 2 diabetes in whom metformin or glibenclamide monotherapy fails, saxagliptin is no safer or more effective than other gliptins. It has a worse safety profile, with many long-term uncertainties and a high potential for drug interactions. It is better to continue with better-assessed treatment strategies.
Full review (5 pages) available for download by subscribers.

Abstract

  • Sitagliptin and vildagliptin are dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as "gliptins".  They are approved for use as oral glucose-lowering agents, although they have no proven impact on morbidity or mortality. Their glucose-lowering effect is limited and their long-term risks are poorly documented.   A third gliptin, saxagliptin, is now authorised in the European Union for second-line treatment of type 2 diabetes, in combination with metformin, a glucose-lowering sulphonylurea, or a glitazone.
  • Clinical evaluation of saxagliptin is mainly based on 8 double-blind randomised trials in about 5000 patients, including 4 trials of second-line combination therapy (1 non-inferiority trial versus sitagliptin, and 3 placebo-controlled trials).
  • The reduction in the mean HbA1c levels with saxagliptin was about 0.3% to 0.8% (in absolute values) versus placebo, which is similar to that reported with other gliptins.
  • The adverse effect profile of saxagliptin is similar to that of the other gliptins, and includes infections (especially urinary tract and sinus infections), gastrointestinal disorders, musculoskeletal disorders, fatigue, and depression. There also appears to be an increased risk of bone fractures. 
  • Potential long-term adverse effects include infectious, cardiac, hepatic, pancreatic and cutaneous disorders.
  • Unlike the other gliptins, saxagliptin is metabolised by the cytochrome P450 isoenzyme CYP 3A4, hence a high potential for pharmacokinetic interactions.
  • The risk-benefit balance of saxagliptin is no better than that of other gliptins, and saxagliptin carries a higher risk of drug interactions. In practice, when metformin or glibenclamide monotherapy fails, it is better to continue with a standard treatment strategy, such as resorting to insulin or abandoning strict glycaemic control.

©Prescrire February 2011

"Saxagliptin. No more effective than other glitazones, but a higher potential for drug interactions" Prescrire Int 2011; 20 (113): 33-37. (Pdf, subscribers only)
Download the full review