Saxagliptin Not Linked to Increased Cancer Risk

In the SAVOR-TIMI 53 cohort, saxagliptin did not appear to increase the risk for cancer or death from cancer.

BOSTON — In the SAVOR-TIMI 53 cohort, saxagliptin did not appear to increase the risk for cancer or death from cancer during approximately 2 years of follow-up, according to research presented at the American Diabetes Association (ADA) 75th Scientific Sessions.

“With regards to antihyperglycemic agents and cancer, very few large randomized controlled trials have  directly assessed the effect of specific antihyperglycemic agents on cancer risk in patients with type 2 diabetes,” Lawrence A. Leiter, MD, FRCPCP, FACP, FAHA, of Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital in Toronto, said during a presentation.

Therefore, the objective of this analysis was to compare overall incidence of overall and specific cancers and malignancy deaths in the placebo and saxagliptin study arms of the SAVOR TIMI 53 cohort.

SAVOR was a large cardiovascular (CV) safety study evaluating about 16,500 patients with type 2 diabetes aged older than 40 years with HbA1c levels above 6.5% and established CVD or multiple risk factors for CVD. In the trial, patients were randomly assigned to saxagliptin (n=8,240) or placebo (n=8,173). The primary endpoint was CV death, MI or ischemic stroke.

Overall, after 2.1 years of follow-up, 362 cancers occurred in patients on placebo (53%) and 326 in patients on saxagliptin (47%; HR=0.89). Among the 12 most common cancers, there were no significant differences between study arms, with the exception of patients on saxagliptin developing fewer colon cancers than those on placebo. However, Leiter noted that this finding should not be overinterpreted given the small number of events.

Though the baseline characteristics were balanced between the saxagliptin and placebo groups, Leiter said there were differences in baseline characteristics between those who developed cancer and those who did not.

Those who developed cancer were less likely to be female and somewhat older. They also tended to have slightly lower HbA1c, lower diastolic blood pressure (BP), lower estimated glomerular filtration rate (eGFR) and were less likely to have established atherosclerosis.

The researchers also assessed differences in developing cancer based on baseline use of various vasculoprotective therapies.

Data indicated that usage of statins was higher in patients who developed cancer vs. those who did not, but Leiter emphasized that this was not corrected for differences in baseline characteristics.

In terms of cancer incidence based on gender, more men than women developed cancer, with no significant differences between those on saxagliptin vs. placebo.

Also, as expected, the researchers found increasing cancer incidence with increasing age, with fewer cancers observed in those aged 65 years on saxagliptin. Even so, Leiter cautioned against overinterpreting this finding due to the small number of cancers.

Duration of diabetes also did not appear to influence the likelihood of developing cancer. Those who had diabetes for less than 5 years had a significantly lower risk for developing cancer on saxagliptin, but Leiter again pointed out that the small number of cases may be a limitation.

When looking at baseline medications, there were no differences, except those using ACE inhibitors or angiotensin II receptor blockers (ARBs) were less likely to develop cancer on saxagliptin than placebo.

Cancer mortality did not differ significantly between the saxagliptin and placebo groups when assessed by gender. Similar to cancer incidence, mortality increased with increasing age, with no differences between treatment arms. Once again, a significant reduction in cancer mortality was found in patients with a duration of diabetes of less than 5 years who were taking saxagliptin.

Baseline medications also did not appear to affect cancer mortality in either study group, Leiter reported.

The researchers performed multivariate modeling for risk for any cancer and found that the most important predictors were male gender, history of dyslipidemia and being a current smoker.

“Stratification by gender, age, race/ethnicity, diabetes duration, baseline HbA1c and pharmacotherapy did not reveal any clinically meaningful differences between the two study arms,” Leiter said.

“In conclusion, the use of saxagliptin was neutral with regards to incidence of cancer or cancer mortality in the large high cardiovascular risk SAVOR-TIMI 53 type 2 diabetes cohort over a median follow-up of 2.1 years. But, of course, the findings are limited by the relatively small number of individual cancer types and short duration of follow-up.”


  1. Leiter LA et al. Abstract 11-OR: Saxagliptin and Cancer in the SAVOR-TIMI 53 Trial. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.