March 2023

GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

J Clin Endocrinol Metab. 2023; online ahead of print DOI: 10.1016/j.jacc.2022.07.021 10.1210/clinem/dgad076

Although the beneficial effects of GLP-1RAs on major cardiovascular events have been established in patients with T2D, their effects on cerebrovascular outcomes remain undetermined.

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Efficacy and Safety of the SGLT2 Inhibitor Empagliflozin versus Placebo and the DPP-4 Inhibitor Linagliptin versus Placebo in Young People with Type 2 Diabetes (DINAMO): a Multicentre, Randomised, Double-blind, Parallel Group, Phase 3 Trial

Lancet Diabetes Endocrinol. 2023; online ahead of print DOI: 10.1016/S2213-8587(22)00387-4

The incidence of T2D in young people is increasing, but treatments remain limited. The double-blind DINAMO trial was conducted in 158 young people (aged 10−17 years) with T2D (HbA1c 6.5-10.5%) who had been previously treated with metformin or insulin. Participants were initially randomised to empagliflozin 10 mg, linagliptin 5 mg or placebo. Participants in the empagliflozin group who did not reach HbA1c <7.0% by week 12 were re-randomised at week 14 to either remain on empagliflozin 10 mg or have their dose increased to 25 mg. Participants in the placebo group were randomised at week 26 to linagliptin 5 mg or one of the empagliflozin doses (10 mg or 25 mg).

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February 2023

Effects of Finerenone in Persons with CKD and T2D are Independent of HbA1c at Baseline, HbA1c Variability, Diabetes Duration and Insulin Use at Baseline

Diabetes Obes Metab. 2023; online ahead of print DOI: 10.1111/dom.14999

Given the role of HbA1c, diabetes duration and insulin use in determining morbidity and mortality of CKD in T2D, it is important to investigate whether these factors modify the efficacy and safety of therapies that mitigate the cardiorenal impact of CKD in T2D. This post hoc analysis of the FIDELITY database evaluated the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression.

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Including Measures of Chronic Kidney Disease to Improve Cardiovascular Risk Prediction by SCORE2 and SCORE2-OP

Eur J Prev Cardiol. 2023;30:8–16 DOI: 10.1093/eurjpc/zwac176

The 2021 ESC guideline on CVD prevention categorises moderate and severe CKD as high and very-high CVD risk status regardless of other factors like age and does not include eGFR and albuminuria in its SCORE2 and SCORE2-OP algorithms to predict CVD risk. Here, three CKD ‘Add-ons' to SCORE2 and SCORE2-OP were developed and validated: eGFR only, eGFR + urinary albumin-to-creatinine ratio (the primary Add-on), and eGFR + dipstick proteinuria.

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Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study

Diabetes Care. 2023; online ahead of print DOI: 10.2337/dc22-1514

Achieving optimal glucose control can be challenging in patients with T2D and CKD because impaired kidney function hampers the use of several oral or injectable glucose-lowering therapies (GLTs) and increases the likelihood of hypoglycaemia. This prespecified analysis from the DAPA-CKD trial evaluated whether the benefits of dapagliflozin in patients with T2D and CKD varied by background GLT number or class.

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January 2023

Effect of Finerenone on Ambulatory Blood Pressure in Chronic Kidney Disease in Type 2 Diabetes

J Hypertens. 2023;41:295–302 DOI: 10.1097/HJH.0000000000003330

It has been postulated that the effects of finerenone on cardiorenal outcomes may be mediated primarily via non-haemodynamic pathways, but office BP measurements are insufficient to fully assess haemodynamic effects. A substudy of the ARTS-DN phase IIb trial was conducted to obtain further insights into the mechanism of action of finerenone by analysing 24-h ambulatory BP in patients with CKD and T2D.

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Efficacy of Empagliflozin in Heart Failure with Preserved versus Mid-range Ejection Fraction: a Pre-specified Analysis of EMPEROR-Preserved

Nat Med. 2022;28:2512–2520 DOI: 10.1038/s41591-022-02041-5

Results from EMPEROR-Preserved demonstrated that empagliflozin improved CV death and HF hospitalisation – the primary outcome – in patients with HF and LVEF >40%. This pre-specified analysis of EMPEROR-Preserved aimed to evaluate the effect of empagliflozin in patients with HFpEF (LVEF ≥50%) compared with patients who had HFmrEF (LVEF 41–49%).

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Empagliflozin, Irrespective of Blood Pressure, Improves Outcomes in Heart Failure with Preserved Ejection Fraction: the EMPEROR-Preserved Trial

Eur Heart J. 2022; online ahead of print DOI: 10.1093/eurheartj/ehac693

Results from EMPEROR-Preserved demonstrated that empagliflozin improved CV and renal outcomes in patients with HFpEF, but its efficacy and safety with baseline SBP is not well established.

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December 2022

Empagliflozin in Black Versus White Patients with Heart Failure: Analysis of EMPEROR-Pooled

Circulation. 2022; online ahead of print DOI: 10.1161/CIRCULATIONAHA.122.062644

While analyses from DAPA-HF and EMPEROR-Reduced demonstrated a consistent benefit of SGLT2i in Black patients, data were limited to HFrEF and included a small number of Black patients. In the current analysis, the efficacy and safety of empagliflozin according to Black vs White race in the Americas was assessed across the spectrum of EF in EMPEROR-Pooled, a combined dataset from both EMPEROR trials.

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