Search

Abstract Background Studies that have reported lower risk for cardiovascular outcomes in users of Sodium–Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). Methods and results Adults initiating empagliflozin and DPP-4i in 2014–2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64–0.86), CVM (HR 0.55; 95% CI 0.38–0.80), HHF or CVM (HR 0.57; 95% CI 0.48–0.67) and stroke (HR 0.79; 95% CI 0.67–0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. Conclusion These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.

Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients with T2D when examining routine clinical practice data from Nordic countries.

Abstract Background Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM). Methods The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed. Results After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI − 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference − 0.33 V (95% CI − 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA1c did not confound the associations. Conclusions Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA1c. Trial registration The protocol was approved by the Regional Committee on Biomedical Research Ethics (H–D-2007-112), the Danish Medicines Agency and registered with ClinicalTrials.gov (NCT00657943).

Introduction Lifetime risk and lifetime lost to diabetes are measures of current diabetes burden in a population. We aimed at quantifying these measures in the Danish population.Research design and methods We modeled incidence and mortality of type 1 diabetes (T1D) and type 2 diabetes (T2D) and non-diabetes mortality based on complete follow-up of the entire population of Denmark in 1996–2016. A multistate model with these transition rates was used to assess the lifetime risk of diabetes, as well as the difference in expected lifetime between persons with type 1 and T2D and persons without.Results In 2016, the lifetime risk of T1D was 1.1% and that for T2D 24%, the latter a 50% increase from 1996. For 50-year-old persons, the lifetime lost was 6.6 years for T1D and 4.8 years for T2D. These figures have been declining over the study period.At 2016, the total foreseeable lives lost in Denmark among patients with T1D were 182 000 years, and those among patients with T2D were 766 000 years, corresponding to 6.6 and 3.0 years per person, respectively.Conclusion At the individual level, improvements in the disease burden for both T1D and T2D have occurred. At the population level, the increasing number of patients with T2D has contributed to a large increase in the total loss of lifetime.

Poor adherence to medication therapy among type 2 diabetes patients is a clinical challenge. We aimed to determine which factors are associated with the three phases of long-term adherence to medication: initiation, implementation and discontinuation in a register-based study.Adherence to six medicine groups (metformin, sulfonylureas, acetylsalicylic acid, thiazide diuretics, renin angiotensin system inhibitors, and statins) were analysed among 5,232 patients with type 2 diabetes at a tertiary referral hospital during 1998-2009. Rate-ratios of initiation of treatment, recurrent gaps in supply of medication, and discontinuation of treatment were analysed using Poisson regression.Poor initiation rather than poor implementation or discontinuation was the main contributor to medication nonadherence. Polypharmacy was a risk factor for slower initiation of treatment for all six medicine groups (rate ratio ranging 0.79 95%CI [0.72-0.87] to 0.89 95%CI [0.82-0.96] per already prescribed medicine), but once patients were in treatment, polypharmacy was not associated with recurrence of gaps in supply of medication, and polypharmacy was associated with lower risk of discontinuation (rate ratio ranging 0.93 95%CI [0.86-1.00] to 0.96 95%CI [0.93-0.99] per prescribed medicine). Other identified risk factors for slow initiation, poor implementation, and discontinuation were diabetes duration, younger age, and Turkish/Pakistani origin.This study showed that a risk factor does not necessarily have the same association with all three elements of adherence (initiation, implementation and discontinuation), and that efforts supporting patients introduced to more complex drug combinations should be prioritized.

OBJECTIVE:The Inuit population in Greenland has undergone rapid socioeconomic and nutritional changes simultaneously with an increasing prevalence of obesity. Therefore, the objective was to examine fetal programming as part of the aetiology of obesity among Inuit in Greenland by investigating the association between birth weight and measures of body composition and fat distribution in adulthood. METHODS:The study was based on cross-sectional data from a total of 1,473 adults aged 18-61 years in two population-based surveys conducted in Greenland between 1999-2001 and 2005-2010. Information on birth weight was collected from birth records. Adiposity was assessed by anthropometry, fat mass index (FMI), fat-free mass index (FFMI), and visceral (VAT) and subcutaneous adipose tissue (SAT) estimated by ultrasound. The associations to birth weight were analyzed using linear regression models and quadratic splines. Analyses were stratified by sex, and adjusted for age, birthplace, ancestry and family history of obesity. RESULTS:Spline analyses showed linear relations between birth weight and adult adiposity. In multiple regression analyses, birth weight was positively associated with BMI, waist circumference, FMI, FFMI and SAT with generally weaker associations among women compared to men. Birth weight was only associated with VAT after additional adjustment for waist circumference and appeared to be specific and inverse for men only. CONCLUSIONS:Higher birth weight among Inuit was associated with adiposity in adulthood. More studies are needed to explore a potential inverse association between birth size and VAT.

The Lexis class in the R package Epi provides an object-based framework for managing follow-up time on multiple time scales, which is an important feature of prospective epidemiological studies with long duration. Follow-up time may be split either into fixed time bands, or on individual event times and the split data may be used in Poisson regression models that account for the evolution of disease risk on multiple time scales. The summary and plot methods for Lexis objects allow inspection of the follow-up times.

The Lexis class in the R package Epi provides tools for creation, manipulation and display of data from multi-state models. Transitions between states are described by rates (intensities); Lexis objects represent this kind of data and provide tools to show states and transitions annotated by relevant summary numbers. Data can be transformed to a form that allows modelling of several transition rates with common parameters.