Articles in 2025

The November 2025 issue marks 20 years since the launch of Nature Reviews Endocrinology (originally Nature Clinical Practice Endocrinology & Metabolism). Here, we reflect on the past 20 years and consider what the future holds.

Neurodegeneration is not merely determined by local cues but is also influenced by systemic signals, such as factors released by peripheral tissues. Muscle-to-brain communication via muscle-secreted signalling factors is increasingly recognized as an important signalling axis. Collectively, muscle-to-brain signalling could be harnessed to impede neurodegeneration and delay cognitive decline during ageing.

This Review explores the translation of senotherapeutics into clinical practice for metabolic disorders. The authors discuss the relationship between metabolic disorders and cellular senescence, current and emerging therapies, and the challenges of translating senotherapeutics into clinical practice for metabolic disorders.

Oestrogen is a key regulator in many metabolic processes, particularly in adipose tissue. This Review discusses the role of oestrogen in adipose tissue metabolism and its wider implications for systemic metabolic health.

In this Review, the authors cover how leptin and melanocortin signalling affect the response to infection by regulating immune cells and the nervous system. The authors also discuss how these signalling pathways might be targeted to improve this response and the potential adverse effects that should be considered as these treatments are investigated.

This Review describes the metabolic functions of high-density lipoproteins (HDLs) and the structural and functional changes that they undergo in diabetes mellitus. The authors discuss how diabetes mellitus reduces the ability of HDLs to act as antioxidants, control inflammation and reduce the risk of cardiovascular disease.

FDA approval of the selective HIF2α inhibitor belzutifan for advanced phaeochromocytoma and paraganglioma (PPGL) is an important milestone in precision oncology. This achievement underscores the power of scientific collaboration in establishing HIF2α as a central driver of PPGL pathogenesis and offers hope for a historically underserved group of patients.

Future treatment targets for type 1 diabetes mellitus will be truly normal blood levels of glucose with a minimum of exogenous insulin and no hypoglycaemia. Here, we present some of the landmark trials from the past 20 years that are driving progress to that goal.

In the past decade, the therapeutic scope of sodium–glucose cotransporter 2 (SGLT2) inhibitors has expanded beyond glycaemic regulation in the management of type 2 diabetes mellitus. In this Review, Lim et al. discuss data from clinical studies of SGLT2 inhibitors, demonstrating their multifaceted cardiovascular, metabolic and renal effects, and elucidate the diverse mechanisms underpinning these benefits.

In this Review, the authors discuss the mechanisms by which diabetes mellitus can lead to kidney damage and describe the clinical characteristics of diabetic kidney disease. The Review also covers current treatments for diabetic kidney disease and new therapies that are being developed.

Molecular biology and omics-based approaches over the past 20 years have rapidly advanced the discipline of exercise metabolism. Here, we examine three innovative human metabolic studies that have increased our understanding of exercise’s complex molecular landscape in skeletal muscle and beyond, and highlight key future directions.

Wearable molecular sensors hold promise for improving patient care; however, challenges in translating the technology to real-world settings remain. This Perspective outlines some of these challenges and discusses potential solutions, particularly in the context of clinical endocrinology.