Sodium Glucose Cotransporter-2 Inhibitor Treatment and the Risk of Diabetic Ketoacidosis in Denmark: A Retrospective Cohort Study of Five Years of Use.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with increased risk of diabetic ketoacidosis (DKA) in both people with type 1 and type 2 diabetes mellitus. Few studies using data from high-quality registries exist that attempt to determine the real- world impact of the increasing use of this drug. OBJECTIVE: The aim of this study was to investigate the incidence and risk of DKA in connection with SGLT2i treatment in Denmark between 2013-2017. METHODS: A nationwide retrospective cohort of people with type 2 diabetes mellitus using SGLT2i or glucagon-like peptide-1 receptor agonists (GLP1-RA) was established and analysed using both Cox-proportional hazard regression and Kaplan-Meier survival analysis. RESULTS: The 37,058 individuals included in the cohort, were made up of SGLT2i (10,923), GLP1- RA (18,849), SGLT2i+insulin (2,069), and GLP1-RA+insulin (10,178) users. The incidence rate (IR) of DKA was 0.84 (95% CI 0.49-1.44) and 0.53 (95% CI 0.36-0.77) for the SGLT2i and GLP1-RA groups, respectively. There was no statistically significant increase in the risk for DKA with SGLT2i use (HR 1.02, 95% CI, 0.44-2.36). However, for the SGLT2i+insulin and GLP1- RA+insulin groups, IRs were 3.47 (95% CI 1.92-6.27) and 0.97 (95% CI 0.68-1.37) respectively, and the risk was statistically significantly higher (HR 5.42, 95% CI 2.16-13.56). CONCLUSION: We observed no significant increase in the risk of DKA for SGLT2i users compared to GLP1-RA. However, a significantly higher IR of DKA was observed with concomitant insulin use, and the risk of DKA was considerably higher for the SGLT2 group using insulin.

Age at hip fracture and life expectancy in Denmark - Secular trends over two decades.

BACKGROUND: Recent improvements in the health of the oldest old coexist with a decline in hip fracture rates, in particular in women. We speculated that increased longevity with decreasing hip fracture rates would result in a delay in hip fracture. We conducted an analysis of time trends in the age at hip fracture, by type and gender, for the past two decades using national data. STUDY POPULATION AND METHODS: We used data from the Danish Hospital Discharge Register (1996-2017) to analyse the age distribution of femoral neck (FN) and pertrochanteric fractures (PT), allowing only the first fracture at each of these two sites to contribute to the analysis in each calendar year. Demographics for the background population at risk including life expectancy tabulations, were also obtained. RESULTS: The average age at FN fracture in women increased slowly but significantly by 0.035years - or 12.8 days - per calendar year [0.035, 95% CI (0.016; 0.054), p<0.001], resulting in an increase from 79.6 to 80.4 years. There were no significant changes in the age at FN fracture in men or the age at PT fracture in women and men. Further, increases in life expectancy were considerably faster than any change observed in the age at hip fracture. In 1996, the average age at FN or PT fracture exceeded the average life expectancy in both men and women whereas the opposite was the case from 2009 and onwards in men and 2015 and onwards in women. CONCLUSION: This study demonstrates a significant change in the demographics of hip fractures in Denmark over the past two decades. We observed a significant increase in the age at FN fracture in women but not in men, with no significant increase in the age at IT fracture and PT fracture. This developed much more slowly, however, than the increase in life expectancy in both sexes observed over the same period of time. Taken together, these changes resulted in a large decrease in the female to male incidence rate ratio from 2.6 and 2.5 (FN and PT, respectively) to 1.9 and 1.7.Additional effort is required to prevent hip fractures to ensure that the increasing life expectancy is matched by a similar increase in hip-fracture free life expectancy.