NEWS

Low Risk of Pancreatitis and Pancreatic Cancer with Saxagliptin

June 25, 2014

By Lorraine L. Janeczko

NEW YORK - In type 2 diabetics treated with saxagliptin for two years, the risk for pancreatitis was low and similar to the risk with placebo - and there was no increased risk for pancreatic cancer, Israeli researchers say.

"Saxagliptin is a relatively safe drug regarding the risk of developing pancreatitis and pancreatic cancer in patients with type 2 diabetes. Although the findings were not 100% conclusive, the cases of pancreatitis and pancreatic cancer were rare and the positive outcome in the rare cases was encouraging: 90% of the patients recovered within two weeks and no cases were life-threatening," said lead author Dr. Itamar Raz of Hadassah Hebrew University Hospital in Jerusalem.

"We actually expected these findings," he said.

"The advantages of this drug over the alternatives are that that saxagliptin was shown to be more efficient than conventional therapy in lowering hemoglobin A1c (HbA1c) and it reached target goals of therapy without causing hypoglycemia," said Dr. Raz, who corresponded with Reuters Health by email. "Saxagliptin has a positive influence on the prevention of the progression of diabetic nephropathy, is weight-neutral and is relatively safe regarding hypoglycemia."

Dr. Raz and colleagues looked at data from the multicenter SAVOR-TIMI 53 trial, which evaluated the long-term cardiovascular (CV) safety and efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin in type 2 diabetics who were at high risk for CV events.

The trial was conducted over about 3 years in 788 medical centers in 26 countries.

Eligible patients had an HbA1c between 6.5% and 12.0% (48-108 mmol/mol) during the six months before they enrolled in the study and were taking any non-incretin-based antidiabetic medication. They were either age 40 and up with established CV disease, or men age 55 or more or women age 60 or more with one or more CV risk factors (dyslipidemia, hypertension or active smoking).

Altogether, nearly 16,500 patients were randomized to receive saxagliptin 5 mg/day or placebo. Patients with moderate or severe renal failure had their saxagliptin dose decreased to 2.5 mg/day.

Over more than two years, while patients continued their usual medical care, they were followed with at least one office visit every 6 months and either an additional phone call or office visit every 3 months.

As reported online June 9 in Diabetes Care, there were 33 patients with pancreatitis in the treatment group and 30 in the control group (hazard ratio 1.09, p=0.80).

In the saxagliptin vs placebo groups, respectively, there was no difference in rates of confirmed cases of definite acute pancreatitis; of definite plus possible pancreatitis; or of chronic pancreatitis.

There were five cases of pancreatic cancer in the saxagliptin group and 12 in the placebo group (p=0.09).

There were no differences between the groups in time to event onset, accompanying pancreatitis risk factors, causality from study medication or disease severity, and outcome.

The author called for further studies to completely resolve the issue of pancreatic safety with incretin-based therapy.

The United States Food and Drug Administration (FDA) has expressed concern about the possible dangers of incretin mimetic drugs for type 2 diabetes. In a March 14, 2013 statement, the agency reported on possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes (http://1.usa.gov/1wtOLz9).

And this year, in a February 11th statement, the FDA expressed concern about saxagliptin and heart failure risk (http://1.usa.gov/1iCyEwj).

Bristol-Myers Squibb and AstraZeneca funded the study. The authors wrote that the sponsors were involved in the study design, data collection and analysis, and that they were given the opportunity to review the manuscript but not to change any aspect of it.

Dr. Raz and several other authors disclosed relationships with Bristol-Myers Squibb and AstraZeneca, as well as other pharmaceutical companies.

SOURCE: http://bit.ly/1qHxAK1

Diabetes Care 2014.

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