SGLT2-inhibition and Vascular Euphoria a Reconciliation of Vascular Health and Disease Homeostasis.

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.

Quantitative measure of asymptomatic cardiovascular disease risk in Type 2 diabetes: Evidence from Indian outpatient setting.

BACKGROUND: The cardiovascular (CV) risk of patients with Type 2 diabetes (T2D) of Indo-Asian descent has never been objectively assessed, although it is documented that they have a higher prevalence of CV disease (CVD). AIMS: To identify groups of Indian patients with asymptomatic T2D who are at high risk of CVD as per the QRISK calculator. METHOD: After an adequate power calculation, a nation-wide study of patients with asymptomatic T2D was conducted. The QRISK3 scores of these patients were used to derive a 10-year risk of CV events. High CVD risk was defined as ≥20% risk of CV event in 10 years. RESULTS: For a total of 1538 patients across 154 outpatient departments, the QRISK3 scores were collated. Median 10-year CVD risk was 22.2%. Mean 10-year CVD risk was 28.4% (standard deviation 22.1%), representing a 5.7-fold increase vs. controls (i.e., matched healthy adults). Absolute CVD risk increased linearly with age. Over 50% of T2D males aged above 45 years had a high (>20%) CVD risk. Women aged more than 55 years had a high risk of CVD. More than 50% of patients with a T2D duration of more than 5 years had a high risk of CVD as per the QRISK3 calculator.

Basic and Clinical Pharmaco-Therapeutics of SGLT2 Inhibitors: A Contemporary Update.

Clinical relevance of sodium/glucose cotransporter 2 (SGLT2) inhibitors has been rapidly evolving across several therapy areas, apart from type 2 diabetes mellitus. While some of these developments are based on recognized scientific explanations, unexpected study findings have also shaped much of our present understanding. As the role of these agents evolves in various facets of cardiology, nephrology, hepatology and endocrinology, their optimum clinical value propositions should be realized in line with the principles of personalized medicine. An updated pharmaco-ergonomic qualification tool, based on the present evidence with these agents, would be a step in this direction. This review describes the present evidence on diverse pharmacological and therapeutic aspects for various SGLT2 inhibitors, as an attempt to provide useful guidance for optimum application in clinical practice.

Sodium-glucose Cotransporter 2 Inhibitor Use: A Pharmaco-ergonomic Qualification Tool.

Pharmaco-ergonomics implies tailoring the drug therapy to an individual patient's requirement(s). The development of sodium-glucose cotransporter 2 inhibitor (SGLT2-i) agents has impelled multiple clinical considerations, in the management of type-2 diabetes. This paper attempts to summarize the pharmaco-ergonomic considerations for these agents, in the form of an SGLT2-i qualification tool, based on a clinical score. This tool may serve as a simple and inexpensive practical guide, to optimize the risk-benefit considerations for SGLT2-i agents.

Diabetes Destiny in our Hands: Achieving Metabolic Karma.

Karma is the ancient Indian philosophy of cause and effect, which implies that an individual's intentions, and actions, both have consequences. None can escape the consequences of one's actions. Applying the principle of karma to medicine and healthcare, the significance of optimal and timely interventions at various stages of disease, may be realized. A holistic approach to metabolic control in diabetes translates into improved clinical outcomes, as evident from the result of STENO-2, EMPA-REG OUTCOME, or LEADER trials. The principle of karma in the management of diabetes may have implications at the transgenerational level during pregnancy and nursing, at the individual patient-level based on phenotype, and at the community level in preventive medicine. The concept of metabolic karma can be used as an effective motivational tool to encourage better health care seeking behavior and adherence to prescribed interventions.

SGLT2-inhibitors in type-2 diabetes: The remaining questions!

As the SGLT2-i therapy progressively carves out a forte in the management of diabetes, multiple equally significant questions justly occupy the medical mind. Aspects pertinent to the influence of this therapy on the renal pathophysiology, the prevention of cardiovascular disease, and considerations for their safe use, hold immense relevance to clinical practice. This review attempts to make an appropriate clinical interpretation of the existing evidence, to evolve a practical perspective on some of these yet unanswered aspects.

Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect.

This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

Clinical Pharmacology of Alpha-1 Blockers Improving Drug-profile through Novel Formulations.

Clinical pharmacology is an essential consideration in chronic therapies, and may play a significant role in modifying the pharmacological characteristics of drug formulations. Improvement in drug formulations may ensure their safe and effective use over a period of time. This has been particularly observed with α-1 adrenergic blockers in hypertension management. Advancements in formulations like prazosin GITS, have resulted in improvement in tolerability profile and smoother, more effective blood pressure control, which reasonably translate into improvement in patient compliance and better clinical outcomes.