Cardiovascular Outcomes with Two “Gliptin” Drugs

September 2, 2013

Cardiovascular Outcomes with Two “Gliptin” Drugs

  1. Allan S. Brett, MD

In fairly short studies, saxagliptin and alogliptin neither decreased nor increased the incidence of major adverse CV events.

  1. Allan S. Brett, MD

In two industry-sponsored, randomized, international trials, investigators examined the effect of dipeptidyl peptidase–4 (DPP-4) inhibitors on the primary endpoint of cardiovascular-related death, myocardial infarction, or stroke in patients with type 2 diabetes. The studies were conducted in response to the FDA's requirement that cardiovascular safety be demonstrated for new diabetes drugs.

In one trial, 16,500 patients (mean age, 65; median duration of diabetes, 10 years) with additional cardiovascular risk factors or known cardiovascular disease received saxagliptin (Onglyza) or placebo. During average follow-up of 2 years, the primary endpoint occurred with near-identical frequency in the two groups (7.3% and 7.2%). No differences in secondary cardiovascular endpoints were noted, except for slightly higher incidence of heart failure hospitalizations with saxagliptin (3.5% vs. 2.8%; P=0.007). Mean glycosylated hemoglobin (HbA1c) was 0.2% lower in the saxagliptin group than in the placebo group, and hypoglycemia was more common with saxagliptin (15.3% vs. 13.4%; P<0.001).

In the other trial, 5400 diabetic patients who had suffered acute coronary syndrome during the previous 3 months received either alogliptin (Nesina) or placebo. During median follow-up of 1.5 years, the incidence of the primary endpoint was 11.3% with alogliptin and 11.8% with placebo, indicating noninferiority (but not superiority) of alogliptin. Alogliptin lowered HbA1c by 0.3% compared with placebo but did not increase risk for hypoglycemia.


Some people will emphasize that these “gliptin” drugs seem relatively safe, with no major adverse cardiovascular effects (although the unexpected slight excess of heart failure cases with saxagliptin should be noted). Others will emphasize that the drugs failed to improve cardiovascular outcomes. Either way, the appropriate role for these drugs remains unclear, given their very high cost (about US$4000 annually) and uncertainty about their long-term effects on clinically meaningful outcomes.

Editor Disclosures at Time of Publication

  • Disclosures for Allan S. Brett, MD at time of publication Nothing to disclose


Reader Comments (2)


There seems to be so little long term outcome evidence of any medication of type II diabetes over metformin or added to metformin. This in spite of many millions in research and billions in profits. Lifestyle and the microbiome appear more important than whatever drug is used, but a new prescription impresses many patients that the physician is doing something.

Julka Physician, Endocrinology, Synergy

For developing nations where. cost of therapy is borne by the patient and is a determinant of compliance this my be good news in disguise as we physicians won't be obliged to write the expensive drugs. For some they may be appropriate but for the majority of our patients who do well on meformi n a d a suck ylurea

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