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Diabetes mellitus, a disease that affects hundreds of millions of people worldwide, is increasing in prevalence in all age groups, including children and adolescents. Much of the morbidity and mortality associated with diabetes is closely related to hypertension, often coincident with diabetes. Comorbid hypertension and diabetes often worsen the outcomes of each other, likely rooted in some overlapping pathogenic mechanisms. In this educational review, we will discuss the shared pathophysiology of diabetes and hypertension, particularly in regard to inflammation and oxidative stress, the sympathetic nervous system, vascular remodeling, and the renin–angiotensin–aldosterone system (RAAS). We will also review current hypertension diagnosis and management guidelines from many international jurisdictions for both adult and paediatric populations in the setting of diabetes. Many of these guidelines highlight the use and utility of RAAS blockers in this clinical scenario; however, on review of the evidence for their use, several meta-analyses and systematic reviews fail to demonstrate superiority of RAAS blockers over other anti-hypertensive medications. Finally, we discuss several new anti-hypertensive medications, review their mechanisms of action, and highlight some of the evidence for their use in the setting of hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is an antidiabetic agent with cardiac and renal protective properties. Its renal protective property is a result of the inhibition of tubular sodium reabsorption and reduction in the intraglomerular pressure. The use of SGLT2 inhibitor in chronic kidney disease (CKD) independent of diabetic status is emerging. However, the real-world data of SGLT2 inhibitor utilisation in CKD is limited. We conducted a descriptive study of patients with CKD, who were prescribed with SGLT2 inhibitor in our Nephrology Clinic. A total of 156 patients were initiated on SGLT2 inhibitor from 2017 to 2022. Among them, 58.3% were male, with a mean age of 61 ± 13 years, and 86.5% had diabetes mellitus, with estimated mean glomerular filtration rate (eGFR) of 46.41 ± 21.14 ml/min/1.73m², and proteinuria of 2.22 ± 2.62 g/day. A total of 85.9% of patients were on renin-angiotensin-system (RAS) blockers, whereby those who were not prescribed with RAS were mostly CKD stage 4. Among the non-diabetic patients, 81% had glomerulonephritis, half of which was IgA nephropathy, and 42.9% were on immunosuppressants. There was a significant retardation of eGFR decline over a six-month-duration after the initiation of SGLT2 inhibitor from -3.46 ± 6.56 ml/ min/1.73m² to -0.77 ± 7.97 ml/min/1.73m± (p=0.001). The retardation of eGFR decline was more pronounced in more advanced CKD stages. However, the proteinuria reduction was insignificant over a six-month-duration (-0.03 ± 2.31 g/day). There were no adverse events reported. In conclusion, SGLT2 inhibitor retarded the eGFR decline with minimal proteinuria reduction in short-term. Nonetheless, long-term efficacy and safety data of SGLT2 inhibitor in local populations requires further evaluation. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is one of the main public health care problems worldwide. It is associated with a marked increased risk of developing atherosclerotic vascular disease, heart failure, chronic kidney disease and death. It is essential to act during the early phases of the disease, through the intensification of lifestyle changes and the prescription of those drugs that have been shown to reduce these complications, with the aim not only of achieving an adequate metabolic control, but also a comprehensive vascular risk control. In this consensus document, developed by the different specialists that treat these patients (endocrinologists, primary care physicians, internists, nephrologists and cardiologists), a more appropriate approach in the management of patients with T2DM or its complications is provided. A particular focus is given to the global control of cardiovascular risk factors, the inclusion of weight within the therapeutic objectives, the education of patients, the deprescription of those drugs without cardiovascular benefit, and the inclusion of GLP-1 receptor agonists and SGLT2 inhibitors as cardiovascular protective drugs, at the same level as statins, acetylsalicylic acid, or renin angiotensin system inhibitors. [ABSTRACT FROM AUTHOR]

Sodium glucose transporters (SGLTs) belong to the mammalian solute carrier family SLC5. This family includes 12 different members in human that mediate the transport of sugars, vitamins, amino acids, or smaller organic ions such as choline. The SLC5 family belongs to the sodium symporter family (SSS), which encompasses transporters from all kingdoms of life. It furthermore shares similarity to the structural fold of the APC (amino acid-polyamine-organocation) transporter family. Three decades after the first molecular identification of the intestinal Na+-glucose cotransporter SGLT1 by expression cloning, many new discoveries have evolved, from mechanistic analysis to molecular genetics, structural biology, drug discovery, and clinical applications. All of these advances have greatly influenced physiology and medicine. While SGLT1 is essential for fast absorption of glucose and galactose in the intestine, the expression of SGLT2 is largely confined to the early part of the kidney proximal tubules, where it reabsorbs the bulk part of filtered glucose. SGLT2 has been successfully exploited by the pharmaceutical industry to develop effective new drugs for the treatment of diabetic patients. These SGLT2 inhibitors, termed gliflozins, also exhibit favorable nephroprotective effects and likely also cardioprotective effects. In addition, given the recent finding that SGLT2 is also expressed in tumors of pancreas and prostate and in glioblastoma, this opens the door to potential new therapeutic strategies for cancer treatment by specifically targeting SGLT2. Likewise, further discoveries related to the functional association of other SGLTs of the SLC5 family to human pathologies will open the door to potential new therapeutic strategies. We furthermore hope that the herein summarized information about the physiological roles of SGLTs and the therapeutic benefits of the gliflozins will be useful for our readers to better understand the molecular basis of the beneficial effects of these inhibitors, also in the context of the tubuloglomerular feedback (TGF), and the renin-angiotensin system (RAS). The detailed mechanisms underlying the clinical benefits of SGLT2 inhibition by gliflozins still warrant further investigation that may serve as a basis for future drug development. [ABSTRACT FROM AUTHOR]

Drugs that inhibit the sodium-glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by ≈30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin-angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR-Reduced trial is well-positioned to determine if the addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction. [ABSTRACT FROM AUTHOR]