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Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, an-tagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including inter-section points to the new generation of antidiabetic drugs. We provide insight into the effective-ness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Purpose Cardiovascular risk factors such as hypertension or dyslipidemia can influence the incidence and progression of diabetic retinopathy (DR) and diabetic macular edema (DME). The aim of this study is to describe the comorbidities in patients with DME. Methods Prospective, monocentric observational study. Patients presenting for the treatment of DME received laboratory and clinical examinations including 24-hour blood pressure measurement. Results Seventy-five consecutive patients were included in the study. The mean age was 61.0 ± 14.5 years, and 83% had type 2 diabetes. The mean body mass index (BMI) was 32.8 ± 6.0 kg/m2. Overweight (BMI ≥ 25 kg/m2) was present in 92% of all patients. HbA1c values were > 7.0% in 57%. Although 87% of the patients already received antihypertensive therapy, the blood pressure (BP) of 82% was still above the recommended target values of systolic < 140 mmHg and diastolic < 80 mmHg. An insufficient nocturnal fall of the systolic BP (< 10%, non-dipping or reverse dipping) was observed in 62%. In 83% of the patients the glomerular filtration rate was ≤ 90 ml/min/1.73m2. Despite 65% of the cohort already receiving lipid-lowering therapy, LDL cholesterol was above the target value of 1.4 mmol/l in 93%. All patients had at least one cardiovascular risk factor in addition to diabetes (overweight, hypertension, insufficient nocturnal BP fall, dyslipidemia, or renal dysfunction) and 86% had ≥ 3 risk factors. Conclusion DME patients are characterized by highly prevalent cardiovascular risk factors that are poorly controlled. These comorbidities reduce the prognosis and negatively influence existing DR and DME. The data reveal an important opportunity for improving patient care by interaction of the ophthalmologist with the general practitioner and internal specialists for the detection and treatment of these conditions.

Inhibition of sodium‐glucose cotransporter 2 (SGLT2) represents an emerging pharmaceutical approach for the treatment of heart failure. The mechanisms by which SGLT2 inhibitors reduce the risk of heart failure are not well understood. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the SLC5A2 gene, encoding SGLT2, and heart failure, and to assess potential mediators of this association. Regression and mediation analyses were conducted with individual participant data of the UK Biobank (n = 416,737) and validated in the cardiovascular high‐risk cohort of the LUdwigshafen RIsk and Cardiovascular Health study (LURIC; n = 3316). Two intronic SNPs associated with SLC5A2 expression were included in a genetic score, which was associated with lower risk of heart failure in UK Biobank (odds ratio 0.97, 95% confidence interval, 0.95−0.99, P = 0.016). This association was also present in participants without type 2 diabetes or coronary artery disease (CAD). The associations of the genetic score with HbA1c, high‐density lipoprotein cholesterol, uric acid, systolic blood pressure, waist circumference, and body composition mediated 35% of the effect of the score on heart failure risk. No associations of the genetic SGLT2 score with atherosclerotic cardiovascular disease outcomes or markers of volume status were observed, which was confirmed in the LURIC study. Variations in the gene encoding SGLT2 were associated with the risk of prevalent or incident heart failure. This association was mediated by several mechanisms and did not depend on the presence of type 2 diabetes or previous CAD events.

International audience; There is an unmet clinical need to reduce residual cardiovascular risk attributable to apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein and remnant particles. Pharmacological targeting of messenger RNA represents an emerging, innovative approach. Two major classes of agents have been developed—antisense oligonucleotides and small interfering RNA. Early problems with their use have been overcome by conjugation with N-acetylgalactosamine, an adduct that targets their delivery to the primary site of action in the liver. Using these agents to inhibit the translation of key regulatory proteins such as PCSK9, apolipoprotein CIII, apolipoprotein(a), and angiopoietin-like 3 has been shown to be effective in attenuating dyslipidemic states. Cardiovascular outcome trials with N-acetylgalactosamine–conjugated RNA-targeting drugs are ongoing. The advantages of these agents include long dosing intervals of up to 6 months and the potential to regulate the abundance of any disease-related protein. Long-term safety has yet to be demonstrated in large-scale clinical trials.

Additional file 2: Table S1. Kaplan-Meier analyses for apolipoproteins and other lipid parameters.