In the Journals

Onglyza does not increase risk for hospitalized heart failure

Recent findings published in the Annals of Internal Medicine showed that Onglyza did not increase the risk for hospitalized heart failure compared with other antihypergylcemic agents.

“The cardiovascular safety of [dipeptidyl pedtidase-4 (DPP-4)] inhibitors has recently become a subject of considerable debate due to the conflicting findings from several large postmarketing trials,” Sengwee Toh, ScD, associate professor of population medicine at Harvard Medical School, and colleagues wrote.

According to the researchers, the SAVOR-TIMI 53 trial showed an increased risk for hospitalized HF related to Onglyza (saxagliptin, AstraZeneca). However, the EXAMINE and TECOS trials did not demonstrate a higher risk for hospitalized HF associated with Januvia (sitagliptin, Merck) or Nesina (alogliptin, Takeda). Despite the conflicting results, the FDA recommended a new safety labelling for saxagliptin last year.

To examine whether saxagliptin or sitagliptin could increase the risk for hospitalized HF, the researchers performed a retrospective study of 78,553 adult saxagliptin users and 298,124 adult sitagliptin users and compared them with patients who initiated therapy with pioglitazone, second-generation sulfonylureas or long-acting insulin products between 2006 and 2013. The researchers performed a disease risk score (DRS)-stratified analysis that compared hospitalized HF risk for each medication individually.

In the disease risk score analyses, the researchers found that saxagliptin did not increase hospitalized HF risk compared with sitagliptin (HR = 0.83; 95% CI, 0.7-0.99), pioglitazone (HR = 0.63; 95% CI, 0.47-0.85), sulfonylureas (HR = 0.69; 95% CI, 0.54-0.87) or insulin (HR = 0.61; 95% CI, 0.5-0.73). They also found that sitagliptin did not increase risk compared with pioglitazone (HR = 0.74; 95% CI, 0.64-0.85), sulfonylureas (HR = 0.86; 95% CI, 0.77-0.95) or insulin (HR = 0.71; 95% CI, 0.64-0.78).

In addition, results showed no increased hospitalized HF risk for these medications in patient subgroups with or without prior cardiovascular disease, the researchers wrote.

The researchers listed four differences between their trial and SAVOR-TIMI 53 that could have led to the differing results. The first was confounding variables such as obesity or smoking that are incompletely captured in health plan databases and could have differed between studies. The second was study population characteristics: In this study, patients were 8 years younger on average, were less likely to have a history of HF and had less concurrent insulin use. The third was that SAVOR-TIMI 53 compared saxagliptin with placebo instead of comparing it directly to other antihyperglycemic agents. Lastly, there was a shorter follow-up in this study, which averaged 1 year, compared with a median follow-up of 2.1 years in the SAVOR-TIMI 53 study.

“Our findings are clinically relevant because patients and physicians often choose among various treatment alternatives (including no treatment) for [type 2 diabetes] in practice,” Toh and colleagues wrote. “Well-designed randomized trials with [hospitalized] HF as the main end point or observational studies that address the limitations of our study will help provide more definitive evidence on this topic.” – by Will Offit

Disclosure s : Toh reports grants from the FDA during the conduct of the study. Please see the full study for a list of all other authors’ relevant financial disclosures.

Recent findings published in the Annals of Internal Medicine showed that Onglyza did not increase the risk for hospitalized heart failure compared with other antihypergylcemic agents.

“The cardiovascular safety of [dipeptidyl pedtidase-4 (DPP-4)] inhibitors has recently become a subject of considerable debate due to the conflicting findings from several large postmarketing trials,” Sengwee Toh, ScD, associate professor of population medicine at Harvard Medical School, and colleagues wrote.

According to the researchers, the SAVOR-TIMI 53 trial showed an increased risk for hospitalized HF related to Onglyza (saxagliptin, AstraZeneca). However, the EXAMINE and TECOS trials did not demonstrate a higher risk for hospitalized HF associated with Januvia (sitagliptin, Merck) or Nesina (alogliptin, Takeda). Despite the conflicting results, the FDA recommended a new safety labelling for saxagliptin last year.

To examine whether saxagliptin or sitagliptin could increase the risk for hospitalized HF, the researchers performed a retrospective study of 78,553 adult saxagliptin users and 298,124 adult sitagliptin users and compared them with patients who initiated therapy with pioglitazone, second-generation sulfonylureas or long-acting insulin products between 2006 and 2013. The researchers performed a disease risk score (DRS)-stratified analysis that compared hospitalized HF risk for each medication individually.

In the disease risk score analyses, the researchers found that saxagliptin did not increase hospitalized HF risk compared with sitagliptin (HR = 0.83; 95% CI, 0.7-0.99), pioglitazone (HR = 0.63; 95% CI, 0.47-0.85), sulfonylureas (HR = 0.69; 95% CI, 0.54-0.87) or insulin (HR = 0.61; 95% CI, 0.5-0.73). They also found that sitagliptin did not increase risk compared with pioglitazone (HR = 0.74; 95% CI, 0.64-0.85), sulfonylureas (HR = 0.86; 95% CI, 0.77-0.95) or insulin (HR = 0.71; 95% CI, 0.64-0.78).

In addition, results showed no increased hospitalized HF risk for these medications in patient subgroups with or without prior cardiovascular disease, the researchers wrote.

The researchers listed four differences between their trial and SAVOR-TIMI 53 that could have led to the differing results. The first was confounding variables such as obesity or smoking that are incompletely captured in health plan databases and could have differed between studies. The second was study population characteristics: In this study, patients were 8 years younger on average, were less likely to have a history of HF and had less concurrent insulin use. The third was that SAVOR-TIMI 53 compared saxagliptin with placebo instead of comparing it directly to other antihyperglycemic agents. Lastly, there was a shorter follow-up in this study, which averaged 1 year, compared with a median follow-up of 2.1 years in the SAVOR-TIMI 53 study.

“Our findings are clinically relevant because patients and physicians often choose among various treatment alternatives (including no treatment) for [type 2 diabetes] in practice,” Toh and colleagues wrote. “Well-designed randomized trials with [hospitalized] HF as the main end point or observational studies that address the limitations of our study will help provide more definitive evidence on this topic.” – by Will Offit

Disclosure s : Toh reports grants from the FDA during the conduct of the study. Please see the full study for a list of all other authors’ relevant financial disclosures.