Data from the SAVOR-TIMI 53 trial showed that saxagliptin lowered HbA1c, improved microvascular disease and did not affect the pancreas, according to experts who presented safety data relevant to endocrinologists from the trial at the ongoing EASD 2013 meeting.
“SAVOR TIMI 53 confirms the overall safety profile of saxagliptin in patients with long disease duration, broad HbA1c levels between 6% and 12%, various antidiabetic medications except incretin therapy, concomitant cardiovascular disease and other medical comorbidities,” Itamar Raz, MD, head of the diabetes unit, department of medicine, Hadassah University Medical Center, Jerusalem, said in a press conference. “The most interesting is that, all together, you can say that this is a safe drug.”
The double blind study that looked at 16,492 patients randomly assigned to saxagliptin (Onglyza, Bristol-Myers Squibb) 5 mg per day or placebo was designed with the primary endpoints of CV death, myocardial infarction and ischemic stroke, but offers additional information for endocrinologists treating patients with diabetes. After 1,040 events occurred, the trial ended. Median duration was 2.1 years.
“In spite of the fact that the principal investigators were supposed to bring patients to target HbA1c in both arms, you can see that when we added saxagliptin, we always have a better blood glucose control, which gets better and better as HbA1c gets higher and higher,” Raz said.
Mean HbA1C was lower in saxagliptin vs. placebo (7.6% vs. 7.9% at 1 year, and 7.5% vs. 7.8% at 2 years). Similarly, attainment of HbA1c <7% was higher with saxagliptin vs. placebo (38.4% vs. 27.5% of patients at 1 year, and 40% vs. 30% at 2 years).
Deepak L. Bhatt
“It’s important to realize that these changes in glycemic control were in the context of a 23% reduction in the intensification of anti-hyperglycemic medications with saxagliptin compared to control, [and] … a 30% reduction in the initiation of insulin therapy for more than 3 months with saxagliptin compared to control,” Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School said in his presentation.
Besides glucose control, Raz said 13% of patients with microalbuminuria (30-300 mg/g) progressed to microalbuminuria (>300 mg/g) when treated with saxagliptin as compared with 16% of placebo-treated patients. Improvement from microalbuminuria to normoalbuminuria (<30 mg/g) was seen in 11% of saxagliptin-treated patients and 9% of placebo-treated patients.
“We are not even sure that the effect that we got was related to blood glucose control because this was not so very impressive,” Raz said. “So, it seems that this drug, by different mechanisms, can have a protective effect on the kidney.”
Raz said more patients treated with saxagliptin were classified as having any level of hypoglycemia (15.3% vs. 13.4% in the placebo group, P=.001), most of these being minor. Saxagliptin significantly increased the risk for major hypoglycemia in patients treated with sulfonylurea and a baseline HbA1c <7%, he said.
Lastly, Raz said saxagliptin showed no signs of pancreatic risk from pancreatitis or pancreatic cancer. Data showed five cases of pancreatic cancer in the saxagliptin group and 12 cases in the placebo group.
Of 63 reported cases of pancreatitis, an external committee confirmed 24 cases in saxagliptin-treated patients and 21 in placebo-treated patients (P=.77); 17 vs. nine were acute (P=.17); and two vs. six (P=.18) were chronic. Raz said of these pancreatitis cases, 61.5% of patients in the saxagliptin group and 48% of patients in the placebo group continued treatment.
“In 2-year follow-up, we don’t see any signs that these drugs will cause or will accelerate cancer,” he said. “Any way we look at it, it doesn’t seem that there is any increase in risk from pancreatitis.”
For more information:
Raz I. Both presented at: 49th Annual Meeting of the European Association for the Study of Diabetes; Sept. 24-27, 2013; Barcelona, Spain.
Disclosure: The study was funded by AstraZeneca and Bristol-Myers Squibb. Raz reports serving on an advisory board, consulting and is on the speakers’ bureau for AstraZeneca/Bristol-Myers Squibb. Bhatt reports relationships with various pharmaceutical and device companies.