Association of Cardiovascular Outcomes and Mortality With Sustained Long-Acting Insulin Only vs Long-Acting Plus Short-Acting Insulin Treatment.

Importance: Cardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes. Objective: To compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin. Design, Setting, and Participants: This retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019. Exposures: Long-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level. Main Outcomes and Measures: Mortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure. Results: Among 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality. Conclusions and Relevance: Findings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.

Comparison of Mortality and Major Cardiovascular Events Among Adults With Type 2 Diabetes Using Human vs Analogue Insulins.

Importance: The comparative cardiovascular safety of analogue and human insulins in adults with type 2 diabetes who initiate insulin therapy in usual care settings has not been carefully evaluated using machine learning and other rigorous analytic methods. Objective: To examine the association of analogue vs human insulin use with mortality and major cardiovascular events. Design, Setting, and Participants: This retrospective cohort study included 127 600 adults aged 21 to 89 years with type 2 diabetes at 4 health care delivery systems who initiated insulin therapy from January 1, 2000, through December 31, 2013. Machine learning and rigorous inference methods with time-varying exposures were used to evaluate associations of continuous exposure to analogue vs human insulins with mortality and major cardiovascular events. Data were analyzed from September 1, 2017, through June 30, 2018. Exposures: On the index date (first insulin dispensing), participants were classified as using analogue insulin with or without human insulin or human insulin only. Main Outcomes and Measures: Overall mortality, mortality due to cardiovascular disease (CVD), myocardial infarction (MI), stroke or cerebrovascular accident (CVA), and hospitalization for congestive heart failure (CHF) were evaluated. Marginal structural modeling (MSM) with inverse probability weighting was used to compare event-free survival in separate per-protocol analyses. Adjusted and unadjusted hazard ratios and cumulative risk differences were based on logistic MSM parameterizations for counterfactual hazards. Propensity scores were estimated using a data-adaptive approach (machine learning) based on 3 nested covariate adjustment sets. Sensitivity analyses were conducted to address potential residual confounding from unmeasured differences in risk factors across delivery systems. Results: The 127 600 participants (mean [SD] age, 59.4 [12.6] years; 68 588 men [53.8%]; mean [SD] body mass index, 32.3 [7.1]) had a median follow-up of 4 quarters (interquartile range, 3-9 quarters) and experienced 5464 deaths overall (4.3%), 1729 MIs (1.4%), 1301 CVAs (1.0%), and 3082 CHF hospitalizations (2.4%). There were no differences in adjusted hazard ratios for continuous analogue vs human insulin exposure during 10 quarters for overall mortality (1.15; 95% CI, 0.97-1.34), CVD mortality (1.26; 95% CI, 0.86-1.66), MI (1.11; 95% CI, 0.77-1.45), CVA (1.30; 95% CI, 0.81-1.78), or CHF hospitalization (0.93; 95% CI, 0.75-1.11). Conclusions and Relevance: Insulin-naive adults with type 2 diabetes who initiate and continue treatment with human vs analogue insulins had similar observed rates of major cardiovascular events, CVD mortality, and overall mortality.

Impact of chemotherapy in women with metastatic breast cancer diagnosed 1990-2003.

PURPOSE: In order to determine whether new treatments for advanced breast cancer resulted in improved survival, we analyzed treatment and survival trends in 232 women with metastatic breast cancer treated in the Minneapolis/St. Paul metropolitan area between 1990 and 2003. PATIENTS AND METHODS: Subjects were identified from area hospital tumor registries and the Minnesota Department of Health. Data on demographics, estrogen receptor status, location of metastases, and treatment were obtained from hospital tumor registries and medical records. RESULTS: A total of 95 patients were diagnosed between 1990 and 1995, and 137 were diagnosed between 1996 and 2003. Overall, there was no difference in survival for women treated between 1990 and 1995 and those treated from 1996 to 2003 (13 months vs. 19 months; P = .38). Chemotherapy recipients in the latter cohort had significantly longer survival than chemotherapy recipients in the earlier cohort (13 months vs. 29 months; P = .03). There were no differences found in survival between cohorts for women receiving hormonal therapy only (18 months vs. 16 months; P = .81). CONCLUSION: We conclude that newer chemotherapeutic agents have had an impact on survival in women with metastatic breast cancer. Newer hormonal agents did not have the same impact on survival in our study.