Introduction People with type 2 diabetes have increased risk of dementia. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (RAs) are among the promising therapies for repurposing as a treatment for Alzheimer's disease; a key unanswered question is whether they reduce dementia incidence in people with type 2 diabetes. Methods We assessed exposure to GLP‐1 RAs in patients with type 2 diabetes and subsequent diagnosis of dementia in two large data sources with long‐term follow‐up: pooled data from three randomized double‐blind placebo‐controlled cardiovascular outcome trials (15,820 patients) and a nationwide Danish registry‐based cohort (120,054 patients). Results Dementia rate was lower both in patients randomized to GLP‐1 RAs versus placebo (hazard ratio [HR]: 0.47 (95% confidence interval [CI]: 0.25–0.86) and in the nationwide cohort (HR: 0.89; 95% CI: 0.86–0.93 with yearly increased exposure to GLP‐1 RAs). Discussion Treatment with GLP‐1 RAs may provide a new opportunity to reduce the incidence of dementia in patients with type 2 diabetes.

Aims To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. Methods and results All Danish residents aged 40–89 years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9–2.9) in women vs. 2.5 (CI 2.4–2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11–1.19, P < 0.001). The relative rates of MACE-HF were highest in the youngest and decreased with advancing age for both men and women, but the relative rates were higher in women across all ages, with the highest women-to-men ratio between age 50 and 60 years. Conclusion Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in the modern era.

Background: Heart failure (HF) in patients with type 2 diabetes mellitus (T2D) has received growing attention. We examined the effect of HF development on prognosis compared with other cardiovascular or renal diagnoses in patients with T2D. Methods and Results: Patients with new T2D diagnosis patients were identified between 1998 and 2015 through Danish nationwide registers. At yearly landmark timepoints after T2D diagnosis, we estimated the 5-year risks of death, 5-year risk ratios, and decrease in lifespan within 5 years associated with the development of HF, ischemic heart disease, stroke, peripheral artery disease, and chronic kidney disease. A total of 153 403 patients with newly diagnosed T2D were followed for a median of 9.7 years (interquartile range, 5.8–13.9) during which 48 087 patients died. The 5-year risk ratio of death associated with HF development 5 years after T2D diagnosis was 3 times higher (CI, 2.9–3.1) than patients free of diagnoses (CI, 2.9–3.1). Five-year risk ratios were lower for ischemic heart disease (1.3 [1.3–1.4]), stroke (2.2 [2.1–2.2]), chronic kidney disease (1.7 [1.7–1.8]), and peripheral artery disease (2.3 [2.3–2.4]). The corresponding decrease in lifespan within 5 years when compared with patients free of diagnoses (in months) was HF 11.7 (11.6–11.8), ischemic heart disease 1.6 (1.5–1.7), stroke 6.4 (6.3–6.5), chronic kidney disease 4.4 (4.3–4.6), and peripheral artery disease 6.9 (6.8–7.0). HF in combination with any other diagnosis imposed the greatest risk of death and decrease in life span compared with other combinations. Supplemental analysis led to similar results when stratified according to age, sex, and comorbidity status, and inclusion period. Conclusions: HF development, at any year since T2D diagnosis, was associated with the highest 5-year absolute and relative risk of death, and decrease in lifespan within 5 years, when compared with development of other cardiovascular or renal diagnoses.

Aims We examined cardiovascular outcomes associated with initiation of GLP-1RA versus SGLT-2i treatment in a real-world setting among patients with type 2 diabetes. Methods and Results This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8,913 new users of GLP-1RA and 5,275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was for the composite cardiovascular outcome, 5.6% (95% confidence interval (CI): 5.2–6.1) versus 5.6% (95% CI: 4.8–6.3); cardiovascular mortality, 1.6% (95% CI: 1.3–1.9) versus 1.5% (95% CI: 1.1–1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5–2.0) versus 1.8% (95% CI: 1.2–2.5); myocardial infarction, 2.1% (95% CI: 1.8–2.4) versus 2.1% (95% CI: 1.5–2.6); and stroke, 2.5% (95% CI: 2.2–2.9) versus 2.6% (95% CI: 2.2–3.1). Conclusion In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA versus SGLT-2i was not found to be associated with significant differences in cardiovascular risk.