Diabetes agents taking centre stage, playing to the beats of Canon in D

Since the discovery of insulin treatment in 1921, there has been a century's worth of effort in fighting the war against diabetes. Insulin resistance and relative insulin deficiency, the hallmarks of type 2 diabetes mellitus (T2DM), were long thought to be the key pathways to treat T2DM, thus rationalizing the use of metformin (an insulin sensitiser), sulphonylurea (an insulin secretagogue) and insulin treatment. At the turn of the twenty-first century, new classes of diabetes agents targeting different pathways were introduced to clinical practice, notably the dipeptidyl peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose co-transporter-2 inhibitors (SGLT2i) and amylin analogues. The armamentarium of diabetes agents continued to expand in the last decade, allowing more therapeutic options to tackle T2DM. The currently available 13 classes of diabetes agents are discussed in the review titled “Overview of Diabetes Agents in Cardiovascular Disease: it takes an orchestra to play Tchaikovsky in symphony” Loh et al. (pp. 3–11). This review discussed the recent recommendations by major cardiovascular guidelines that emphasizes SGLT2i and GLP-1 RA to be offered to patients with T2DM and cardiovascular disease (CVD) because of their cardiovascular-metabolic-renal-obesity protective traits as shown in clinical trials. Apart from summarizing the pros and cons of the various diabetes agents, this review also addressed the practical questions about diabetes agents in clinical practice, such as the best time to initiate GLP-1 based therapies, considerations for combination therapies of SGLT2i and GLP-1 RA, and what a holistic approach to T2DM should also entail (apart from CVD risk reduction and glucose control). The doctor managing diabetes is likened to an orchestra's conductor, coordinating and providing patient-centred care to achieve key clinical targets while considering the multi-dimensional aspects that may coexist (e.g. comorbidities, sex differences, psychosocial and cultural). As shown in genetic studies, it is now clear that the wide heterogeneity of clinical presentations and response to treatment amongst patients with diabetes is at least partially attributable to genetics. In a review titled “Precision medicine in diabetes care” by Tan et al. (pp. 12–19), the authors discussed the recent studies on genetic testing, polygenic risk scores and multi-omics that have shown encouraging data in utilizing these precision medicine tools to diagnose, classify and manage monogenic and polygenic forms of diabetes. Asia is the epicentre of T2DM, contributing to more than half of the global prevalence of diabetes. Therefore, a review of the landscape of diabetes in Asia is necessary and timely. In a review titled “Type 2 Diabetes: A Contemporary View from the Asian Lens” by Ratnasingam et al. (pp. 20–25), the authors discussed recent Asian data that showed young-onset diabetes was associated with a higher risk of developing chronic kidney disease and other diabetes complications, when compared with patients that had older-onset diabetes. Asians with diabetes tended to have a higher likelihood of sarcopenia than non-Asian patients. The review also discussed the pharmacogenomics of diabetes treatment, social determinants of health and barriers to treatment in Asia. Whilst there is a large amount of evidence on the use of diabetes agents in the adults with obesity and/or diabetes, there is much less studies in the younger and older populations, hence beckoning a review titled “The role of incretin-based therapies in the management of obesity and diabetes, in the younger and older populations” by Rigas et al. (pp. 26–33). The authors discussed the encouraging results of recent studies that investigated the use of GLP1-RA for obesity in the adolescents and 6 to 12-year-olds. On the other spectrum of age (older patients ≥ 65 years old), the studies suggest GLP1-RA was effective and well tolerated but tended to have higher discontinuation rate compared with adults less than 65 years old because of adverse events. This review also discussed the likely detrimental effects of weight cycling in elderly patients, as elderly tended to regain fat mass instead of lean mass with the weight rebound after weight loss. Apart from the cardiovascular, metabolic, renal, obesity protective traits of selective diabetes agents, there are postulations that some diabetes agents may be associated with neuroprotective effects (e.g. Alzheimer's disease, Parkinson's disease). Possible relationships between diabetes agents and heart-brain axis are discussed in a review titled “Interactions between anti-diabetes medications and heart-brain axis” by Leong and Ching (pp. 34–43). The review discussed the pathogenesis of heart-brain pathology of T2DM, which involves inflammatory pathways. Correspondingly, certain diabetes agents such as metformin, SGLT2i and GLP1-RA, may have neurological and cardioprotective benefits through various anti-inflammatory mechanisms such as AMPK activation (e.g. metformin) and NLRP3 inflammasome inhibition (e.g. SGLT2i). The authors described conflicting mechanisms regarding DPP4i on the cardiovascular system, as DPP4i may activate sympathetic nervous system and worsen heart failure but may also reduce cardiac hypertrophy. In summary, the present issue in the diabetes section of February 2025 focussed on reviews highlighting recent advances in diabetes agents and themes in management. Shifting the focus from a one-size-fit all, the reviews compiled in this issue aimed to discuss deserving areas related to diabetes such as cardiovascular system and CVD, the non-cardiac systems (e.g. brain, renal), the use of precision medicine, Asian studies, and the young and the old. In the cardiometabolic field and beyond, diabetes agents are taking centre stage. The publications of positive studies supporting diabetes agents are increasing at every beat of a music, almost as if they are playing to the rhythm of Pachelbel's Canon in D. To me, that's D for diabetes. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.