Translating trial results into interpretable risk estimates: Systematic analysis of cardiorenal outcome trials of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.

Background And Aims: In a randomised controlled trial (RCT), the between-arm difference in the average probability of an event per unit of time (i.e., yearly incidence risk difference, YIRD) is an easy-to-interpret treatment effect metric.

Effect of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on time to outcome in type 2 diabetes cardiorenal outcome trials.

Introduction: In randomized controlled trials (RCTs), treatment effects are commonly reported as hazard ratio, a measure often misinterpreted as a relative risk reduction. The acceleration factor (AF) indicates the extent to which a treatment increases/decreases the time before the occurrence of an outcome and gives useful insights in the interpretation of trials' results.

Methods: Using individual time-to-event data reconstructed from Kaplan-Meier plots, we estimated AFs for the primary outcomes (POs) and all-cause mortality in glucagon-like peptide-1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2-is) cardiorenal outcome trials in subjects with type 2 diabetes.

The impact of COVID-19 lockdowns on the body mass index of people living with obesity: A UK retrospective cohort study using the UK Clinical Practice Research Datalink.

Background: Restrictions implemented by governments during the coronavirus disease 2019 (COVID-19) pandemic affected people's eating habits and physical activity. We investigated the effect of COVID-19 lockdowns and restrictions on body mass index (BMI) and weight in a UK population, according to BMI class, sex, age and ethnicity.

Methods: This retrospective observational cohort study used the Clinical Practice Research Datalink AURUM database.

Intensive glucose control and recurrent cardiovascular events: 14-year follow-up investigation of the ACCORDION study.

Aims: While cardiovascular disease in patients with type 2 diabetes commonly progresses with the occurrence of repeated events, most trials consider the effect of glucose-lowering strategies only on the first event. We examined the Action to Control Cardiovascular Risk in Diabetes trial and its observational follow-up study (ACCORDION) to investigate the effect of intensive glucose control on multiple events and further identify any subgroup effects.

Materials And Methods: A recurrent events analysis, using a negative binomial regression model, was applied to estimate the treatment effect on different consecutive cardiovascular disease events, including non-fatal myocardial infarction, non-fatal stroke, hospitalisation from heart failure, and cardiovascular death.

Non-inferiority and clinical superiority of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors: Systematic analysis of cardiorenal outcome trials in type 2 diabetes.

Aims: Most trials leading to the approval of glucagon-like peptide receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) were primarily designed to confirm their non-inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.

Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

Background: Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection.

Methods: We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020.

Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.

Objective: To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes.

Methods: Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting).

Microvascular Disease and Risk of Cardiovascular Events and Death From Intensive Treatment in Type 2 Diabetes: The ACCORDION Study.

Objective: To assess whether the presence of microvascular complications modifies the effect of intensive glucose reduction on long-term outcomes in patients with type 2 diabetes.

Patients And Methods: Using ACCORD and ACCORDION study data, we investigated the risk of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) or death in relation to the prerandomization type and extent of microvascular complications. Interaction terms were fitted in survival models to estimate the risk of both outcomes across levels of an overall microvascular disease score (range 0 to 100) and its individual components: diabetic nephropathy, retinopathy, and neuropathy.

Cardiovascular effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: The P value and beyond.

Despite growing awareness of the dangers of a dichotomous interpretation of trial results based on the 'statistical significance' of a treatment effect, the uptake of new approaches has been slow in diabetes medicine. We showcase a number of ways to interpret the evidence for a treatment effect applied to the cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT-2is): the P value function (or confidence curves), which depicts the treatment effect across the whole spectrum of confidence levels; the counternull value, which is the hazard ratio (i.e.

Ethnic minorities and COVID-19: examining whether excess risk is mediated through deprivation.

Background: People from South Asian and black minority ethnic groups are disproportionately affected by the COVID-19 pandemic. It is unknown whether deprivation mediates this excess ethnic risk.

Methods: We used UK Biobank with linked COVID-19 outcomes occurring between 16th March 2020 and 24th August 2020.

Association of Timing and Balance of Physical Activity and Rest/Sleep With Risk of COVID-19: A UK Biobank Study.

Behavioral lifestyle factors are associated with cardiometabolic disease and obesity, which are risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate whether physical activity, and the timing and balance of physical activity and sleep/rest, were associated with SARS-CoV-2 positivity and COVID-19 severity. Data from 91,248 UK Biobank participants with accelerometer data and complete covariate and linked COVID-19 data to July 19, 2020, were included.

Number needed to treat in cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists: A systematic review with temporal analysis.

Cardiovascular outcome trials (CVOTs) investigating the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have highlighted some important differences among these medications. The recent American Diabetes Association and European Association for the Study of Diabetes consensus underlines that each trial constitutes a single experiment; therefore, it remains unclear if, and to what extent, the observed differences reflect the heterogeneous pharmacological properties of each compound. To help clarify the evidence, in this systematic review we investigated differences in trial characteristics which may have had an impact on the primary and secondary trial results, including baseline control of risk factors, prevalence of cardiovascular diseases, absolute rates of events, duration of the study, and definitions of the inclusion criteria and outcomes.

Uses and Limitations of the Restricted Mean Survival Time: Illustrative Examples From Cardiovascular Outcomes and Mortality Trials in Type 2 Diabetes.

The restricted mean survival time (RMST) has been advocated as an alternative or a supplement to the hazard ratio for reporting the effect of an intervention in a randomized clinical trial. The RMST difference allows quantification of the postponement of an outcome during a specified (restricted) interval and corresponds to the difference between the areas under the 2 survival curves for the intervention and control groups. This article presents examples of the use of the RMST in a research and a clinical context.

Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A systematic review and network meta-analysis.

Aim: To compare the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with type 2 diabetes.

Materials And Methods: Electronic databases were searched from inception to 24 April 2019 for randomized controlled trials reporting change in glycated haemoglobin (HbA1c) at approximately 24 and/or 52 weeks for SGLT-2is and/or GLP-1RAs (classified as short- and long-acting). Bayesian network meta-analyses were conducted to compare within and between SGLT-2i and GLP-1RA classes for cardiometabolic efficacy and adverse events (PROSPERO registration number: CRD42018091306).

Efficacy of low- and very-low-energy diets in people with type 2 diabetes mellitus: A systematic review and meta-analysis of interventional studies.

Aims: To review systematically and quantify the weight loss achieved through low- (LEDs) and very-low-energy diets (VLEDs) in people with type 2 diabetes mellitus (T2DM).

Materials And Methods: Studies reporting the effects of diet-only interventions of up to 1600 kcal/d in people with T2DM were searched in MEDLINE, EMBASE and CINAHL up to July 2018. Changes in the primary (body weight and body mass index [BMI]) and secondary outcomes (glycated haemoglobin, blood lipids) according to energy restriction and duration of diet were modelled using restricted cubic splines.