Decreasing rates of major lower-extremity amputation in people with diabetes but not in those without: a nationwide study in Belgium.

AIMS/HYPOTHESIS: The reduction of major lower-extremity amputations (LEAs) is one of the main goals in diabetes care. Our aim was to estimate annual LEA rates in individuals with and without diabetes in Belgium, and corresponding time trends. METHODS: Data for 2009-2013 were provided by the Belgian national health insurance funds, covering more than 99% of the Belgian population (about 11 million people). We estimated the age-sex standardised annual amputation rate (first per year) in the populations with and without diabetes for major and minor LEAs, and the corresponding relative risks. To test for time trends, Poisson regression models were fitted. RESULTS: A total of 5438 individuals (52.1% with diabetes) underwent a major LEA, 2884 people with above- and 3070 with below-the-knee major amputations. A significant decline in the major amputation rate was observed in people with diabetes (2009: 42.3; 2013: 29.9 per 100,000 person-years, 8% annual reduction, p < 0.001), which was particularly evident for major amputations above the knee. The annual major amputation rate remained stable in individuals without diabetes (2009: 6.1 per 100,000 person-years; 2013: 6.0 per 100,000 person-years, p = 0.324) and thus the relative risk reduced from 6.9 to 5.0 (p < 0.001). A significant but weaker decrease was observed for minor amputation in individuals with and without diabetes (5% and 3% annual reduction, respectively, p < 0.001). CONCLUSIONS/INTERPRETATION: In this nationwide study, the risk of undergoing a major LEA in Belgium gradually declined for individuals with diabetes between 2009 and 2013. However, continued efforts should be made to further reduce the number of unnecessary amputations.

Incretin-Based Therapies and the Short-term Risk of Pancreatic Cancer: Results From Two Retrospective Cohort Studies.

OBJECTIVE: Concerns have been raised about a possible increased risk of pancreatic cancer associated with incretin-based therapies. We examined the risk of pancreatic cancer among patients with diabetes prescribed incretin drugs. RESEARCH DESIGN AND METHODS: With the use of public health insurance databases of Belgium and the Lombardy Region, Italy, we created two retrospective cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) from 1 July 2008 to 31 December 2013 in Belgium and from 1 January 2008 to 31 December 2012 in the Lombardy Region. The risk of pancreatic cancer was evaluated by multivariate-adjusted Cox models that included time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled by using fixed-effects meta-analyses. RESULTS: The cohorts included 525,733 patients with diabetes treated with NIADs and 33,292 with incretin drugs. Results in both cohorts were similar. Eighty-five and 1,589 subjects who developed pancreatic cancer were registered among the incretin and NIAD new users, respectively, which represented an aHR of pancreatic cancer of 2.14 (95% CI 1.71-2.67) among those prescribed an incretin compared with an NIAD. The aHR with a drug use lag exposure of 6 months was 1.69 (1.24-2.32). The aHR decreased from 3.35 (2.32-4.84) in the first 3 months after the first incretin prescription to 2.12 (1.22-3.66) in months 3-5.9, 1.95 (1.20-3.16) in months 6-11.9, and 1.69 (1.12-2.55) after 12 months. Among those prescribed an NIAD, pancreatic cancer occurred mostly within the year after the first prescription. The risk of pancreatic cancer among patients subsequently prescribed insulin was 6.89 (6.05-7.85). CONCLUSIONS: The recent prescription of incretin therapy is associated with an increased risk of pancreatic cancer. The reason for such an increase is likely the consequence of an occult pancreatic cancer that provokes or aggravates diabetes. Studies are warranted for assessing the risk of pancreatic cancer associated with long-term use of incretin drugs.