Second-line incretin therapies, including DPP-IV inhibitors and GLP-1 receptor agonists, do not increase the risk for pancreatitis or pancreatic cancer when added to metformin in type 2 diabetes, according to findings published in Diabetic Medicine.
“Treatment with GLP-1 [receptor agonists] is associated with favorable changes in metabolic measurements such as body weight, and some agents in the class have been shown to reduce the risk of cardiovascular events,” Sanjoy Paul, PhD, MSc, of the University of Melbourne and Melbourne Health, Australia, and colleagues wrote. “However, some recent clinical observational studies have raised questions as to the possible association of treatment with incretin-based therapies, particularly with DPP-IV [inhibitors], and the risk of acute pancreatitis or pancreatic cancer.”
Paul and colleagues used the Centricity Electronic Medical Record database to analyze medication data and disease status for 225,898 adults with type 2 diabetes who began metformin treatment as their first antihyperglycemic therapy and followed with a second-line treatment of a DDP-IV inhibitor, GLP-1 receptor agonist, insulin, thiazolidinedione or sulfonylurea (mean age, 59 years; 51% women; 69% white).
Of the total sample, 49% were prescribed sulfonylureas, 22% DPP-IV inhibitors, 15% insulin, 8% TZDs and 6% GLP-1 receptor agonists.
Within the cohort, 1,049 patients developed acute pancreatitis, with rates per 1,000 person-years similar across the DPP-IV inhibitor, GLP-1 receptor agonist and sulfonylurea groups (1.31, 1.49 and 1.31, respectively), according to the researchers.
They also observed similarities in mean time to event across all medications, except insulin, in which the rate per 1,000 person-years of acute pancreatitis was higher (2.01; 95% CI, 1.75-2.31) and the mean time to event was significantly shorter (–0.48 years; 95% CI, –0.9 to –0.06) when compared with DPP-IV inhibitor treatment. The researchers also noted that the rate per 1,000 person-years of acute pancreatitis was lowest in the TZD group (0.89; 95% CI, 0.7-1.12).
Pancreatic cancer was reported in 357 patients, with no significant differences between the five treatment types. The rate in DPP-IV inhibitor group was 0.46 per 1,000 person-years (95% CI, 0.36-0.59), whereas the rates in the GLP-1 receptor agonist (0.17; 95% CI, 0.08-0.36) and TZD groups (0.36; 95% CI, 0.25-0.52) were marginally lower. Rates in the insulin (0.59; 95% CI, 0.46-0.77) and sulfonylurea (0.55; 95% CI, 0.47-0.63) groups were slightly higher. The researchers noted that pancreatic cancer developed in those in the GLP-1 receptor agonists group later (mean time to event, 3 years; 95% CI, 0.84-5.16) vs. the DPP-IV inhibitor group (mean time to event, 2.7 years; 95% CI, 2.19-3.21).
“The findings of this analysis provide reassurance to prescribers and users of DPP-IV [inhibitors] that these medications do not significantly increase the risk of adverse pancreatic outcomes compared with other commonly prescribed second-line therapies,” the researchers wrote. – by Phil Neuffer
Disclosure: Paul reports that he has received grants, consultant or speaking fees from Amylin, AstraZeneca, GI Dynamics, Guangzhou Zhongyi Pharmaceutical, Hospira, Merck, Novartis, Novo Nordisk, Pfizer, Roche and Sanofi.