This study is a follow-up cohort study of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial, which was a randomized, open-label, standard care–controlled trial examining the effects of low-dose aspirin on cardiovascular events. We followed up 2,536 Japanese patients with type 2 diabetes (T2D) enrolled in the JPAD trial from 2002 to 2017. The primary outcome of this post hoc analysis was the incidence of dementia, which was defined by the prescription of antidementia drugs or admission due to dementia.

Among the originally enrolled patients, 2,121 (84%) retained their original allocation. During a median follow-up of 11.4 years, 128 patients developed dementia. The overall effect of low-dose aspirin on the prevention of dementia adjusted for age, sex, and other established risk factors was not significant (hazard ratio [HR] 0.82, 95% CI 0.58–1.16). However, a significant reduction was seen in the risk of dementia in women (HR 0.58, 95% CI 0.36–0.95), but not in men (HR 1.27, 95% CI 0.75–2.13) (P_interaction = 0.03).

Long-term use of low-dose aspirin may reduce the risk for dementia in women with T2D.

Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs.

Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were ~$1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm ($28,907 vs. $30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group ($42,697 vs. $30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time.

Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated.

A cost-effectiveness analysis was conducted to estimate lifetime costs and health gains using a stochastic microsimulation model of oral health conditions, T2D, T2D-related microvascular diseases, and CVD of the U.S. population. Model parameters were obtained from the nationally representative National Health and Nutrition Examination Survey (NHANES) (2009–2014) and randomized trials of periodontal treatment among patients with T2D.

Expanding periodontal treatment coverage among patients with T2D and periodontitis would be expected to avert tooth loss by 34.1% (95% CI –39.9, –26.5) and microvascular diseases by 20.5% (95% CI –31.2, –9.1), 17.7% (95% CI –32.7, –4.7), and 18.4% (95% CI –34.5, –3.5) for nephropathy, neuropathy, and retinopathy, respectively. Providing periodontal treatment to the target population would be cost saving from a health care perspective at a total net savings of $5,904 (95% CI –6,039, –5,769) with an estimated gain of 0.6 quality-adjusted life years per capita (95% CI 0.5, 0.6).

Providing nonsurgical periodontal treatment to patients with T2D and periodontitis would be expected to significantly reduce tooth loss and T2D-related microvascular diseases via improved glycemic control. Encouraging patients with T2D and poor oral health conditions to receive periodontal treatment would improve health outcomes and still be cost saving or cost-effective.

Cox regression models were constructed to analyze 20 years of data from the Danish National Patient Registry with respect to effect of the antihyperglycemic therapies on the three end points.

A total of 66,807 people with type 2 diabetes were treated with metformin (MET) including a combination of second- and third-line therapies. People on MET plus sulfonylurea (SU) had the highest risk of all end points, except for severe hypoglycemia, for which people on MET plus basal insulin (BASAL) had a higher risk. The lowest risk of major adverse cardiovascular events was seen for people on a regimen including a glucagon-like peptide 1 (GLP-1) receptor agonist. People treated with MET, GLP-1, and BASAL had a lower risk of all three end points than people treated with MET and BASAL, especially for severe hypoglycemia. The lowest risk of all three end points was, in general, seen for people treated with MET, sodium–glucose cotransporter 2 inhibitor, and GLP-1.

Findings from this study do not support SU as the second-line treatment choice for patients with type 2 diabetes. Moreover, the results indicate that adding a GLP-1 for people treated with MET and BASAL could be considered, especially if those people suffer from severe hypoglycemia.

This was a cohort study using an active-comparator, new-user design and nationwide register data from Sweden, Denmark, and Norway during 2010–2016. The cohort included 38,731 new users of GLP-1 receptor agonists (liraglutide 92.5%, exenatide 6.2%, lixisenatide 0.7%, and dulaglutide 0.6%), matched 1:1 on age, sex, and propensity score to a new user of the active comparator, dipeptidyl peptidase 4 (DPP-4) inhibitors. The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospitalization for renal events. Secondary outcomes were the individual components of the main outcome. Hazard ratios (HRs) were estimated using Cox models and an intention-to-treat exposure definition. Mean (SD) follow-up time was 3.0 (1.7) years.

Mean (SD) age of the study population was 59 (10) years, and 18% had cardiovascular disease. A serious renal event occurred in 570 users of GLP-1 receptor agonists (incidence rate 4.8 events per 1,000 person-years) and in 722 users of DPP-4 inhibitors (6.3 events per 1,000 person-years, HR 0.76 [95% CI 0.68–0.85], absolute difference –1.5 events per 1,000 person-years [–2.1 to –0.9]). Use of GLP-1 receptor agonists was associated with a significantly lower risk of renal replacement therapy (HR 0.73 [0.62–0.87]) and hospitalization for renal events (HR 0.73 [0.65–0.83]) but not death from renal causes (HR 0.72 [0.48–1.10]). When we used an as treated exposure definition in which patients were censored at treatment cessation or switch to the other study drug, the HR for the primary outcome was 0.60 (0.49–0.74).

In this large cohort of patients seen in routine clinical practice in three countries, use of GLP-1 receptor agonists, as compared with DPP-4 inhibitors, was associated with a reduced risk of serious renal events.

In a post hoc analysis of 14,752 Exenatide Study of Cardiovascular Event Lowering (EXSCEL) participants, we examined time-dependent associations between SHEs and subsequent major adverse cardiac events (CV death, nonfatal myocardial infarction [MI] or stroke), fatal/nonfatal MI, fatal/nonfatal stroke, hospitalization for acute coronary syndrome (hACS), hospitalization for heart failure (hHF), and all-cause mortality (ACM), as well as time-dependent associations between nonfatal CV events and subsequent SHEs.

SHEs were uncommon and not associated with once-weekly exenatide therapy (hazard ratio 1.13 [95% CI 0.94–1.36], P = 0.179). In fully adjusted models, SHEs were associated with an increased risk of subsequent ACM (1.83 [1.38–2.42], P < 0.001), CV death (1.60 [1.11–2.30], P = 0.012), and hHF (2.09 [1.37–3.17], P = 0.001), while nonfatal MI (2.02 [1.35–3.01], P = 0.001), nonfatal stroke (2.30 [1.25–4.23], P = 0.007), hACS (2.00 [1.39–2.90], P < 0.001), and hHF (3.24 [1.98–5.30], P < 0.001) were all associated with a subsequent increased risk of SHEs. The elevated bidirectional time-dependent hazards linking SHEs and a composite of all CV events were approximately constant over time, with those individuals at dual risk showing higher comorbidity scores compared with those without.

These findings, showing greater risk of SHEs after CV events as well as greater risk of CV events after SHEs, validate a bidirectional relationship between CV events and SHEs in patients with high comorbidity scores.

CVD events in the 1,441 DCCT/EDIC participants were analyzed separately by type (CVD death, acute myocardial infarction [MI], stroke, silent MI, angina, percutaneous transluminal coronary angioplasty/coronary artery bypass graft [PTCA/CABG], and congestive heart failure [CHF]) or as composite outcomes (CVD or major adverse cardiovascular events [MACE]). Proportional rate models and conditional models assessed associations between risk factors and CVD outcomes.

Over a median follow-up of 29 years, 239 participants had 421 CVD events, and 120 individuals had 149 MACE. Age was the strongest risk factor for acute MI, silent MI, stroke, and PTCA/CABG, while glycemia was the strongest risk factor for CVD death, CHF, and angina, second strongest for acute MI and PTCA/CABG, third strongest for stroke, and not associated with silent MI. HbA_1c was the strongest modifiable risk factor for a first CVD event (CVD: HR 1.38 [95% CI 1.21, 1.56] per 1% higher HbA_1c; MACE: HR 1.54 [1.30, 1.82]) and also for subsequent CVD events (CVD: incidence ratio [IR] 1.28 [95% CI 1.09, 1.51]; MACE: IR 1.89 [1.36, 2.61]).

Intensive glycemic management is recommended to lower the risk of initial CVD events in T1D. After a first event, optimal glycemic control may reduce the risk of recurrent CVD events and should be maintained.