Itamar Raz1, Deepak L Bhatt2, Boaz Hirshberg3, Ofri Mosenzon4, Benjamin M Scirica2, Amarachi Umez-Eronini2, KyungAh Im2, Christina Stahre5, Alona Buskila4, Nayyar Iqbal6, Norton Greenberger2, Markus M Lerch7. 1. Diabetes Unit, Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel ntv502@netvision.net.il. 2. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 3. AstraZeneca Research and Development, Wilmington, DE. 4. Diabetes Unit, Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel. 5. AstraZeneca Research and Development, Mölndal, Sweden. 6. Bristol-Myers Squibb, Princeton, NJ. 7. University Medicine Greifswald, Greifswald, Germany.
Abstract
OBJECTIVE: To determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial. RESEARCH DESIGN AND METHODS: A total of 16,492 type 2 diabetic patients ≥40 years old with established cardiovascular (CV) disease or CV risk factors were randomized to saxagliptin or placebo and followed for 2.1 years. Outcome measures were investigator reported with blinded expert adjudication of total pancreatitis (acute and chronic) and reported cases of pancreatic cancer. RESULTS: Trial investigators reported 35 events of pancreatitis in each treatment arm in 63 patients (33 [0.40%] in the saxagliptin arm and 30 [0.37%] in control arm), with a hazard ratio (HR) of 1.09 (95% CI 0.66-1.79, P = 0.80). Adjudication confirmed pancreatitis in 24 patients (26 events) in the saxagliptin arm (0.29%) and 21 patients (25 events) in placebo arm (0.26%), with an HR of 1.13 (0.63-2.06, P = 0.77). Cases of definite acute pancreatitis were confirmed in 17 (0.2%) vs. 9 (0.1%) (HR 1.88 [0.86-4.41], P = 0.17), definite plus possible pancreatitis in 22 vs. 16 (HR 1.36 [0.72-2.64], P = 0.42), and chronic pancreatitis in 2 vs. 6 (HR 0.33 [0.05-1.44], P = 0.18) in the saxagliptin and placebo arms, respectively. No differences in time to event onset, concomitant risk factors for pancreatitis, investigator-reported causality from study medication or disease severity, and outcome were found between treatment arms. The investigators reported 5 and 12 cases of pancreatic cancer in the saxagliptin and placebo arms, respectively (HR 0.42 [0.13-1.12], P = 0.09). CONCLUSIONS: In the SAVOR-TIMI 53 trial, within 2.1 years of follow-up, risk for pancreatitis in type 2 diabetic patients treated with saxagliptin was low and apparently similar to placebo, with no sign of increased risk for pancreatic cancer. Further studies are needed to completely resolve the pancreatic safety issues with incretin-based therapy.
RCT Entities:
OBJECTIVE: To determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial. RESEARCH DESIGN AND METHODS: A total of 16,492 type 2 diabeticpatients ≥40 years old with established cardiovascular (CV) disease or CV risk factors were randomized to saxagliptin or placebo and followed for 2.1 years. Outcome measures were investigator reported with blinded expert adjudication of total pancreatitis (acute and chronic) and reported cases of pancreatic cancer. RESULTS: Trial investigators reported 35 events of pancreatitis in each treatment arm in 63 patients (33 [0.40%] in the saxagliptin arm and 30 [0.37%] in control arm), with a hazard ratio (HR) of 1.09 (95% CI 0.66-1.79, P = 0.80). Adjudication confirmed pancreatitis in 24 patients (26 events) in the saxagliptin arm (0.29%) and 21 patients (25 events) in placebo arm (0.26%), with an HR of 1.13 (0.63-2.06, P = 0.77). Cases of definite acute pancreatitis were confirmed in 17 (0.2%) vs. 9 (0.1%) (HR 1.88 [0.86-4.41], P = 0.17), definite plus possible pancreatitis in 22 vs. 16 (HR 1.36 [0.72-2.64], P = 0.42), and chronic pancreatitis in 2 vs. 6 (HR 0.33 [0.05-1.44], P = 0.18) in the saxagliptin and placebo arms, respectively. No differences in time to event onset, concomitant risk factors for pancreatitis, investigator-reported causality from study medication or disease severity, and outcome were found between treatment arms. The investigators reported 5 and 12 cases of pancreatic cancer in the saxagliptin and placebo arms, respectively (HR 0.42 [0.13-1.12], P = 0.09). CONCLUSIONS: In the SAVOR-TIMI 53 trial, within 2.1 years of follow-up, risk for pancreatitis in type 2 diabeticpatients treated with saxagliptin was low and apparently similar to placebo, with no sign of increased risk for pancreatic cancer. Further studies are needed to completely resolve the pancreatic safety issues with incretin-based therapy.