Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have emerged as key therapeutic agents in managing type 2 diabetes mellitus (T2DM) and obesity, offering benefits that extend beyond glycemic control. This review examines the role of SGLT-2 inhibitors in modulating cardiac autonomic function, with a particular focus on heart rate variability (HRV) as a biomarker of autonomic balance. These agents improve metabolic profiles through enhanced glucosuria, natriuresis, and weight loss, while concurrently reducing blood pressure. Importantly, they also attenuate sympathetic nervous system overactivity and promote parasympathetic modulation, which may lower the risk of adverse cardiovascular events. The underlying mechanisms include not only the metabolic effects but also anti-inflammatory and antioxidative actions, which together contribute to improved endothelial function and vascular health. Advanced HRV analyses, encompassing traditional time and frequency domain methods as well as nonlinear approaches, have proven valuable in detecting early autonomic dysfunction in high-risk populations. Some studies suggest that SGLT-2 inhibitors may be associated with improvements in HRV parameters, such as increased SDNN and RMSSD and a reduced LF/HF ratio. However, findings are inconsistent across studies, and further research is needed to determine the extent and mechanisms of these potential effects. Although these findings are promising, further standardized, long-term studies are essential to clarify the mechanisms and optimal therapeutic strategies involving SGLT-2 inhibitors in the management of autonomic dysfunction. Future research should also explore the synergistic potential of combining SGLT-2 inhibitors with other cardiometabolic therapies to enhance cardiovascular outcomes in individuals with and without T2DM.

Schizophrenia (SCZ) represents a considerable health concern, not only due to its impact on cognitive and psychiatric domains, but also because of its association with metabolic abnormalities. Individuals with SCZ face an increased risk of developing metabolic syndrome (MS), which contributes to the increased cardiovascular burden and reduced life expectancy observed in this population. Metabolic alterations are associated with both the SCZ condition itself and extrinsic factors, particularly the use of antipsychotic medications. Additionally, the link between SCZ and MS seems to be guided by distinct genetic parameters. The present narrative review summarizes the relationship between SCZ and MS and emphasizes the various therapeutic approaches for managing its components in patients with these conditions. Recommended therapeutic approaches include lifestyle modifications as the primary strategy, with a focus on behavioral lifestyle programs, addressing dietary patterns and physical activity. Pharmacological interventions include administering common antidiabetic medications and the selection of less metabolically harmful antipsychotics. Alternative interventions with limited clinical application are also discussed. Ultimately, a personalized therapeutic approach encompassing both the psychological and metabolic aspects is essential for the effective management of MS in patients with SCZ.

Although diabetes mellitus is strongly associated with dementia, the mechanism underlying diabetes-induced cognitive dysfunction has not been clarified. Here, we demonstrate the vital role of repulsive guidance molecule A (RGMa) in the regulation of adult hippocampal neurogenesis and cognitive impairment under diabetic conditions. In type 2 diabetic db/db mice and streptozotocin-mediated type 1 diabetic mice, RGMa is upregulated in the granular cell layer of the dentate gyrus. Additionally, both neural stem cells (NSCs) and immature neurons express its receptor, neogenin. In vitro experiments revealed that high glucose-conditioned hippocampal neurons inhibited the differentiation of NSCs, and the application of an anti-RGMa antibody restored it. The treatment with an anti-RGMa antibody ameliorated diabetes-induced cognitive decline and impairment of hippocampal neurogenesis. These findings suggest that the RGMa negatively regulates hippocampal neurogenesis and is involved in diabetes mellitus-induced cognitive decline.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition worldwide resulting from the loss of tolerance against self-antigens. The constitutional symptoms of SLE are well-known, including fatigue, fever, myalgia, weight loss, arthralgia, arthritis, malar rash, and photosensitivity. These symptoms often overshadow the impacts SLE can have on all body systems, with the renal system frequently impacted. Inflammation of the nephrons can progress to end-stage renal disease and renal failure if not treated effectively. Currently, the medications that are being utilized for the treatment of lupus nephritis (LN), include azathioprine, hydroxychloroquine, cyclophosphamide, belimumab, voclosporin, tacrolimus, mycophenylate, and rituximab. However, the majority of these medications are used off-label, and many come with severe side effects. With the additional benefits of anti-diabetic medications being examined outside of their original purpose, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have begun to be investigated for their role in LN. To determine the impact of SGLT-2 inhibitors on LN risk and progression, a preliminary systematic review was conducted. A total of 248 articles were analyzed, with six being selected. SGLT-2 inhibitors were found to improve glomerular filtration rate (GFR), reduce proteinuria and albuminuria, and reduce the inflammatory cascade. The exploration of SGLT-2 inhibitors as a therapeutic strategy for LN represents a promising and innovative approach to managing this complex condition. SGLT-2 inhibitors show potential benefits beyond glycemic control. However, due to the novelty of this treatment and the limited studies completed, further testing is required to analyze its true effectiveness in LN.

Sodium-glucose cotransporters (SGLTs) play a crucial role in glucose regulation and are essential therapeutic targets for diabetes management. Recent advancements have leveraged SGLT-targeted PET imaging to examine these transporters' roles in both health and disease.

This review highlights recent innovations in PET imaging targeting SGLTs, with a particular focus on SGLT-specific radiotracers, such as alpha-methyl-4-deoxy-4-18F-fluoro-d-glucopyranoside (Me-4FDG). It emphasizes the advantages of these radiotracers over conventional 18F-2-fluoro-2-deoxy-d-glucose (2-FDG) imaging, especially in assessing SGLT activity. Additionally, the review addresses their potential in evaluating the pharmacodynamics of SGLT inhibitors, investigating metabolic changes in diabetes, and staging cancers.

SGLT-targeted PET imaging offers promising improvements in diagnostic accuracy and therapeutic planning. The findings underscore the physiological and pathological significance of SGLTs, indicating that this imaging approach could shape future diagnostic and therapeutic strategies in metabolic and oncologic fields.

Diabetes mellitus (DM) is a common comorbidity in total knee arthroplasty (TKA) patients, which has been associated with multiple complications. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are one class of medications recently approved to better manage DM. This study investigates the correlation of SGLT2i use on postoperative complications and revision rates for diabetic patients undergoing TKA.

The M157 PearlDiver database was used to identify DM patients undergoing primary TKA. Those prescribed SGLT2i were identified and matched in 1:4 ratio with control DM patients based on age, sex, obesity diagnosis, and Elixhauser comorbidity index. Ninety-day adverse events and 5-year rates of revision were abstracted and compared by multivariable regression, controlling for age, sex, Elixhauser comorbidity index, long-term insulin use, obesity, metformin use, and active tobacco use.

A total of 164,474 TKA patients with DM were identified, of which SGLT2i were prescribed for 9,246 (5.6%). On multivariable analysis, SGLT2i use in DM patients was independently associated with higher odds of aggregated adverse events driven by myocardial infarction (odds ratio [OR] 2.40), sepsis (OR 1.81), urinary tract infection (OR 2.10), pneumonia (OR 1.87), and acute kidney injury (OR 1.33) but had lower odds of transfusion (OR 0.31) ( P < 0.0001 for each). On multivariable analysis, 5-year survival to revision TKA were not markedly different between the matched cohorts.

SGLT2i are being increasingly prescribed for DM patients undergoing TKA. Although they are associated with increased risk of multiple 90-day perioperative adverse outcomes, they are also associated with reduced incidence of blood transfusion. These results may guide surgical decision making and counseling for patients taking this group of medications and align with some prior studies related to glucagon-like protein-1 agonists.

Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients.

The aim of this study was to investigate the additional effects of empagliflozin on liraglutide in patients with advanced-stage type 2 diabetic kidney disease.

Forty-one patients were randomly assigned (1:1) to treatment with liraglutide alone during the first 6 months and subsequent treatment with liraglutide plus empagliflozin during the next 6 months (liraglutide plus empagliflozin group) (n = 20) or treatment with liraglutide alone for 12 months (liraglutide group) (n = 21). Liraglutide was administered subcutaneously once daily at a starting dose of 0.3 mg/day and up-titrated weekly by 0.3 mg to a maximum dose of 0.9 mg/day. Empagliflozin was administered orally at a dose of 10 mg once daily. The primary outcome was the change in renal function (estimated glomerular filtration rate) during the latter 6 months. Secondary outcomes were changes in body weight, systolic blood pressure, hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio during the latter 6 months.

Empagliflozin significantly increased the hemoglobin concentration (from 12.9 ± 1.9 to 13.7 ± 1.9 g/dL; p<0.05) and decreased body weight (from 66.1 ± 12.9 to 64.5 ± 12.6 kg; p<0.05). No significant differences were observed between the groups for estimated glomerular filtration rate, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio.

Empagliflozin increased hemoglobin concentration and decreased body weight in patients with advanced-stage type 2 diabetic kidney disease who received liraglutide. However, empagliflozin did not provide short-term benefits with regard to renal function decline, urinary protein excretion, or glycemic control in these patients.

Sodium glucose cotransporter 2 inhibitors (SGLT2is) are a newly developed class of anti-diabetics which exert potent hypoglycemic effects in the diabetic milieu. However, the evidence suggests that they also have extra-glycemic effects. The renin-angiotensin-aldosterone system (RAAS) is a hormonal system widely distributed in the body that is important for water and electrolyte homeostasis as well as renal and cardiovascular function. Therefore, modulating RAAS activity is a main goal in patients, notably diabetic patients, which are at higher risk of complications involving these organ systems. Some studies have suggested that SGLT2is have modulatory effects on RAAS activity in addition to their hypoglycemic effects and, thus, these drugs can be considered as promising therapeutic agents for renal and cardiovascular disorders. However, the exact molecular interactions between SGLT2 inhibition and RAAS activity are not clearly understood. Therefore, in the current study we surveyed the literature for possible molecular mechanisms by which SGLT2is modulate RAAS activity.

Metabolic syndrome (MetS), as a set of medical conditions including hyperglycemia, hypertension, abdominal obesity, and dyslipidemia, represents a highly prevalent disease cluster worldwide. The individual components of MetS together increase the risk of MetS-related disorders. Recent research has demonstrated that bone, as an endocrine organ, releases several systemic cytokines (osteokines), including fibroblast growth factor 23 (FGF23), lipocalin 2 (LCN2), and sclerostin (SCL). This review not only summarizes current knowledge about MetS, osteokines and the most common MetS-related diseases with a detrimental impact on bone quality (type 2 diabetes mellitus: T2DM; cardiovascular diseases: CVDs; osteoporosis: OP), but also provides new interpretations of the relationships between osteokines and individual components of MetS, as well as between osteokines and MetS-related diseases mentioned above. In this context, particular emphasis was given on available clinical studies. According to the latest knowledge, FGF23 may become a useful biomarker for obesity, T2DM, and CVDs, as FGF23 levels were increased in patients suffering from these diseases. LCN2 could serve as an indicator of obesity, dyslipidemia, T2DM, and CVDs. The levels of LCN2 positively correlated with obesity indicators, triglycerides, and negatively correlated with high-density lipoprotein (HDL) cholesterol. Furthermore, subjects with T2DM and CVDs had higher LCN2 levels. SCL may act as a potential biomarker predicting the incidence of MetS including all its components, T2DM, CVDs, and OP. Elevated SCL levels were noted in individuals with T2DM, CVDs and reduced in patients with OP. The aforementioned bone-derived cytokines have the potential to serve as promising predictors and prospective treatment targets for MetS and MetS-related diseases negatively affecting bone quality.

Diabetic ketoacidosis (DKA) is a life-threatening condition among diabetic patients characterized by metabolic anion gap (AG) acidosis of arterial pH <7.30, glucose >250 mg/dL, and positive ketones. The triggers for DKA can be infection, surgery, and, in reported cases, intraparenchymal hemorrhage (IPH). In rare cases of DKA, despite being in active ketoacidosis, glucose levels may be within normal or accepted range. Such a condition is called euglycemic DKA. It has been recently recognized in association with the use of sodium glucose co-transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.

An 83-year-old male taking an SGLT-2 inhibitor (empagliflozin) for type 2 diabetes presented with an IPH. His laboratory studies revealed an elevated AG acidosis, an elevated beta hydroxybutyrate, and serum glucose levels within the acceptable range. Urine studies revealed elevated ketones and glucose. The diagnosis of euglycemic DKA was made, and the patient was treated with insulin and glucose infusions.

Like hyperglycemic ketoacidosis, euglycemic DKA requires prompt recognition and immediate aggressive medical therapy, but the diagnosis can be challenging, and the treatment using insulin in the setting of a normal glucose can be counterintuitive. Euglycemic DKA can often be missed in the setting of blood glucose not being elevated. Prompt recognition and treatment are critical for successful management.

The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells. Among them, mTOR and SGLT-2 inhibitors have garnered attention due to their diverse effects: mTOR inhibitors regulate cellular growth, metabolism, and immune responses, while SGLT-2 inhibitors regulate glucose reabsorption in the kidneys, resulting in various beneficial metabolic effects. Importantly, these drugs may act synergistically by influencing senescence processes and pathways. Although direct studies on the combined effects of mTOR inhibition and SGLT-2 inhibition on age-related processes are limited, this review aims to highlight the potential synergistic benefits of these drugs in targeting senescence.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are extensively used in the management of heart failure because of their cardiovascular benefits. Adverse drug reactions associated with dapagliflozin include diabetic ketoacidosis, fungal infections, and increased blood glucose concentrations. However, abnormal uterine bleeding is not a known side effect of dapagliflozin. We report a 75-year-old Chinese woman with dilated cardiomyopathy and chronic heart failure who experienced abnormal uterine bleeding while taking dapagliflozin. Notably, cessation of dapagliflozin administration resulted in the disappearance of uterine bleeding. These findings suggest that dapagliflozin possesses additional potential mechanisms, but these mechanisms require further investigation. Furthermore, healthcare professionals should remain vigilant regarding the occurrence of uterine bleeding when prescribing dapagliflozin.

To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

We performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors.

The FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered.

Although KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA's prescribing information to inform prescribers of this risk.

Despite improvements in glucose monitoring technologies, insulin formulations and insulin delivery systems, too many patients with type 1 diabetes (T1D) continue to struggle to meet their glycemic goals. As a result, they suffer from high rates of microvascular and macrovascular disease. Titration of insulin therapy, while essential to the care of these patients, is often limited by undesirable side effects of hypoglycemia and weight gain. Sodium-glucose cotransporter (SGLT) inhibitors have been proposed as a potential adjunctive therapy to insulin that may offset some of these effects, while simultaneously enabling patients with T1D to potentially reap the cardiovascular and renal benefits afforded by these agents in those with type 2 diabetes. This review summarizes and contextualizes the clinical trial data that has emerged with these agents in this specific population.

A clinical review based on current literature was generated by the authors.

This review summarizes the data from several clinical trial programs investigating the use of SGLT inhibitors in T1D, describing the potential benefits and the ketosis-related adverse events of these agents (including euglycemic DKA), along with a discussion of possible mitigation strategies to reduce this risk.

Although theoretically SGLT inhibitors have the potential to improve metabolic, cardiovascular, and renal outcomes in patients with T1D, the risks of diabetic ketoacidosis currently represent an important limitation to the widespread use of these agents. If treatment is undertaken, caution must be taken, with implementation of effective mitigation strategies being essential.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents.

This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment.

Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n = 10) and DWP SID group (n = 9). In the DWP TOD group, 0.025 mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025 mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups.

No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p < 0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n = 5, DWP SID group n = 5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001.

When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose.

Although the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes mellitus (DM) are well known, their effects in patients without DM continue to be explored. We provide a meta-analysis of the available evidence. Online databases were searched for randomized controlled trials (RCTs) comparing SGLT2i to placebo/control in patients without DM. The end points of interest were composite CV death/hospitalization for heart failure (HF) with individual components, all-cause death, major adverse CV events, and serious adverse events. Subgroup analysis was performed according to the type of SGLT2i. Pooled odds ratios (OR) and 95% confidence intervals (CI) were generated through a random-effects model. A total of 6 RCTs with 12,984 patients (6,501 in the SGLT2i group and 6,483 in the placebo group) were included, followed over a mean duration of 17.7 months. Four RCTs had patients with HF, 1 with chronic kidney disease, and 1 with myocardial infarction. The mean age was 64 years, 72% of patients were men and mean hemoglobin A1C was 5.7%. As compared with a placebo, SGLT2i treatment was associated with significant reduction in composite CV death or hospitalization for HF (OR 0.77, 95% CI 0.68 to 0.87, p <0.0001), primarily because of a decrease in hospitalization for HF (OR 0.70, 95% CI 0.60 to 0.81, p <0.00001). No significant differences were found pertaining to CV death (OR 0.86, 95% CI 0.74 to 1.01, p = 0.06), all-cause death (OR 0.89, 95% CI 0.71 to 1.11, p = 0.29) and major adverse CV events (OR 0.95, 95% CI 0.68 to 1.32, p = 0.75). Serious adverse events were lower with use of empagliflozin vs placebo. In conclusion, this study shows significant CV benefits in terms of reduction in CV death or hospitalization for HF in patients without DM treated with SGLT2i as compared with placebo. The underlying heterogeneity of patients in terms of co-morbidities (HF, chronic kidney disease, or myocardial infarction) needs to be considered while interpreting the results.

Sodium-dependent glucose transporters 2 (SGLT2) inhibitors are a class of small-molecule drugs that have gained significant attention in recent years for their potential clinical applications in the treatment of type 2 diabetes mellitus (T2DM). These inhibitors function by obstructing the kidneys' ability to reabsorb glucose, resulting in a rise in the excretion of glucose in urine (UGE) and subsequently lowering blood glucose levels. Several SGLT2 inhibitors, such as Dapagliflozin, Canagliflozin, and Empagliflozin, have been approved by regulatory authorities and are currently available for clinical use. These inhibitors have shown notable enhancements in managing blood sugar levels, reducing body weight, and lowering blood pressure in individuals with T2DM. Additionally, they have exhibited potential advantages in decreasing the likelihood of cardiovascular incidents and renal complications among this group of patients. This review article focuses on the synthesis and clinical application of small-molecule SGLT2 inhibitors, which have provided a new therapeutic approach for the management of T2DM.

Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall tolerability and established use in diabetes management, SGLT-2i may be a promising candidate for cancer therapy and as a supplementary component to conventional treatments. This narrative review aimed to examine the potential roles and mechanisms of SGLT-2i in the management of diverse types of cancer. Future investigations should focus on elucidating the antitumor efficacy of individual SGLT-2i in different cancer types and exploring the underlying mechanisms. Additionally, clinical trials to evaluate the safety and feasibility of incorporating SGLT-2i into the treatment regimen of specific cancer patients and determining appropriate dosage combinations with established antitumor agents would be of significant interest.

Patients with diabetes are at higher risk of cognitive impairment and memory loss than the normal population. Thus, using hypoglycemic agents to improve brain function is important for diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a class of therapeutic agents used in the management of diabetes that has some pharmacologic effects enabling them to fight against the onset and progress of memory deficits. Although the exact mediating pathways are not well understood, emerging evidence suggests that SGLT2 inhibition is associated with improved brain function. This study reviewed the possible mechanisms and provided evidence suggesting SGLT2 inhibitors could ameliorate cognitive deficits.

The study aimed to compare the effectiveness of oral hypoglycemic agents (OHAs) as monotherapy, dual and quadruple therapy for glycemic control (GC) and glycemic variability (GV) in patients with type 2 diabetes (T2DM) using flash glucose monitoring system (FGM).

Diabetes management largely relies on HbA1c monitoring. Glycemic variability has been an evolving glycemic target for preventing complications related to type 2 diabetes mellitus.

The purpose of the study was to compare glycemic control measures and glycemic variability measures among study groups and to study the relationships between GC and GV indices.

Retrospectively, FGM data were collected from 50 T2DM patients. The patients were classified based on prescribed number of OHAs as monotherapy [group 1: Dipeptidyl peptidase- 4 (DPP-4) inhibitors (n=10), group 2: Sodium-glucose co-transporter-2 (SGLT2) inhibitors (n=10), group 3: Sulphonylureas (n=10), group 4: Dual therapy (n=10), and group 5: Quadruple therapy (n=10)]. Measures of GC and GV were evaluated.

Significant differences between study groups were observed in GC and GV measurements. The SGLT2 inhibitors monotherapy group demonstrated optimal GC [eA1c (%): 6.5 ± 2.2; MBG: 140.80 ± 63.94; TIR: 60.60 ± 19.96] and GV (SD: 42.38 ± 34.57; CV: 27.85 ± 6.68; MAGE: 96.76 ± 52.47; MODD: 33.96 ± 22.91) in comparison to other study groups. On using Pearson correlation analysis, mean blood glucose (MBG) and mean amplitude of glycemic excursion (MAGE) showed moderate correlation (r = 0.742)(r2 = 0.551), depicting distinct glucose variabilities at the same mean blood glucose levels.

The monotherapy group of SGLT2 inhibitors demonstrated glucose-lowering effects with reduced glycemic variability. Hence, optimum glycemic control is associated with decreased glycemic variability.

Canagliflozin (CANA) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor with blood glucose lowering effects. CANA also promotes kidney protection in patients with cardiovascular diseases and type 2 diabetes (T2D), as well as in normoglycemic patients with hypertension or heart failure. Clinical studies, although conduct in both sexes, do not report sex-dependent differences in T2DM treated with CANA. However, the impact of CANA in type 1 diabetes, as well in sex-dependent outcomes in such cohort needs further understanding. To analyze the effects of CANA in mice with combined hypertension and type 1 diabetes, diabetes was induced by STZ injection (5 days, 50mg/kg/day) in both male and female 8 weeks old genetic hypertensive mice (Lin), whereas the control (Lin) received 0.1M sodium citrate injections. 8 weeks after STZ. Mice were fed either regular or CANA-infused diet for 4 weeks. 8 weeks after STZ, hyperglycemia was present in both male and female mice. CANA reversed BG increase mice fed regular diet. Male LinSTZ mice had elevated water intake, urine output, urinary albumin to creatinine ratio (ACR), kidney lesion score, and creatinine clearance compared to the Lin control group. Kidney injury was improved in male LinSTZ + CANA group in male mice. Water intake and urine output were not statistically significantly different in female LinSTZ compared to female LinSTZ+ CANA. Moreover, CANA did not improve kidney injury in female mice, showing no effect in creatinine clearance, lesion score and fibrosis when compared to LinSTZ fed regular diet. Here we show that Canagliflozin might exert different kidney protection effects in male compared to female mice with hypertension and type 1 diabetes. Sex-dimorphisms were previously found in the pathophysiology of diabetes induced by STZ. Therefore, we highlight the importance of in-depth investigation on sex-dependent effects of CANA, taking in consideration the unique characteristics of disease progression for each sex.

Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type 2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal-protective effects and weight-lowering characteristics. However, reports on myopathy secondary to SGLT2 inhibitor treatment raised a safety concern. The importance of maintaining muscle mass in people with T2DM necessitates further investigation to explore the impact of novel medications on body composition. In this review, we discussed current evidence on the impact of SGLT2 inhibitors on body composition in people with T2DM.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.

Type 2 Diabetes Mellitus (T2DM) is a pandemic that affects millions of patients worldwide. Diabetes affects multiple organ systems leading to comorbidities including hypertension. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) recently have been approved for the treatment of T2DM and heart failure with reduced and preserved ejection fraction. Retrospective analyses of clinical trials have noted SGLT2 inhibitors to have a promising effect on blood pressure. Moreover, the observed blood pressure reduction is not just an acute effect of treatment initiation but has been shown to have a long-term impact on both systolic and diastolic blood pressure. The mechanism of action leading to the blood pressure reduction is still unclear; however, proposed mechanisms are related to the natriuretic effect, modification of the renin-angiotensin-aldosterone system, and/or the reduction in the sympathetic nervous system, SGLT2i should be considered as second-line medication in those patients with diabetes or heart disease and concomitant hypertension. This article reviews the pharmacology, side effect profile, and clinical trials surrounding the use of SGLT2i for the treatment of hypertension.

Polycystic ovary syndrome (PCOS) is a common endocrine, reproductive, and metabolic disorder affecting females. The management of PCOS is challenging and current interventions are not enough to deal with all consequences of this syndrome. We explored the beneficial effect of combined sodium glucose co transporter-2 inhibitor (SGLT-2i); (empagliflozin) and metformin on hormonal and metabolic parameters in an animal model of PCOS and insulin resistance (IR). Forty adult female Wistar rats divided into five groups: control, PCOS-IR, PCOS-IR treated with metformin, PCOS-IR treated with empagliflozin, and PCOS-IR treated with combined metformin and empagliflozin. Single modality treatment with metformin or empagliflozin yielded significant improvement in body mass index, insulin resistance, lipid profile, sex hormones, inflammatory markers, and ovarian cystic follicles. Combined metformin with empagliflozin expressed further significant improvement in sex hormones, inflammatory markers with disappearance of ovarian cystic follicles. The superior significant improvement with combined treatment over the single modality was in line with significant improvement in the ovarian AMPKα-SIRT1 expression.

Nano-drug delivery is a rapidly growing approach in medicine that helps design and develop newer forms of drugs with more efficacy and lower adverse effects. Sodium-glucose cotransporter-2 inhibitors are an emerging class of antidiabetic agents that reduce the blood glucose levels by damping glucose reabsorption in renal proximal tubules.

This mechanism might be followed by some adverse effects that could be prevented by nano-drug delivery. Although we have still limited evidence about nanoforms of sodium-glucose cotransporter-2 inhibitors, current knowledge strongly suggests that nanotechnology can help us design more effective drugs with lower side effects. In recent years, several studies have explored the possible benefits of nanoforms of sodium-glucose cotransporter-2 inhibitors. However, clinical trials are yet to be conducted.

In the current review, we present the latest findings on the development and benefits of nanoforms of sodium-glucose cotransporter-2 inhibitors.

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation-reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors-an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.

Evogliptin (EV) is a novel dipeptidyl peptidase-4 inhibitor (DPP4i) for glycemic control in patients with type 2 diabetes mellitus (T2DM). This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between EV and sodium glucose cotransporter-2 inhibitors (SGLT2i) in healthy volunteers since combination therapy of DPP4i and SGLT2i has been considered as an effective option for T2DM treatment. A randomized, open-label, multiple-dose, two-arm, three-period, three treatments, two-sequence crossover study was conducted in healthy Korean volunteers. In arm 1, subjects were administered 5 mg of EV once daily for 7 days, 25 mg of empagliflozin (EP) once daily for 5 days, and the combination once daily for 5 days (EV + EP). In arm 2, subjects were administered 5 mg of EV once daily for 7 days, 10 mg of dapagliflozin (DP) once daily for 5 days, and the combination once daily for 5 days (EV + DP). Serial blood samples were collected for PK analysis, and oral glucose tolerance tests were conducted for PD analysis. In each arm, a total of 18 subjects completed the study. All adverse events (AEs) were mild with no serious AEs. The geometric mean ratio and confidence interval of the main PK parameters (maximum concentration of the drug in plasma at steady state and area under the plasma drug concentration-time curve within a dosing interval at a steady state) between EV and either EP or DP alone were not significantly altered by co-administration. Administration of EV + EP or EV + DP did not result in significant PD changes, as determined by the glucose-lowering effect. Administration of EV + EP or EV + DP had no significant effects on the PK profiles of each drug. All treatments were well-tolerated.

While type 2 diabetes mellitus (T2DM) increases the risk of cardiac complications, diabetes treatment choices may increase or decrease the rates of cardiac events. In the present review, we comprehensively discussed the treatment options of diabetic subjects with cardiac conditions.

Current evidence related to diabetes treatment in cardiac situations has been reviewed. Clinical trials and meta-analyses on cardiac safety of anti-diabetic medicines are discussed. Treatment choices with proven benefits and those at least without associated increased cardiac risk were drawn from clinical trials; meta-analyses and cardiac safety studies in the recent medical literature were the basis of the suggestions in the present review.

We can suggest that hypoglycemia and extreme hyperglycemia should be avoided in acute ischemic heart conditions. Certain diabetic treatment options, especially sodium-glucose cotransporter-2 (SGLT2) inhibitors, can reduce overall cardiovascular mortality and hospitalization due to heart failure. Therefore, we suggest that physicians should choose SGLT2 inhibitors as the first-line treatment option in diabetic patients with heart failure or those who have a high risk of heart failure development. T2DM increases the risk of atrial fibrillation (AF), and metformin and pioglitazone seem to reduce the risk of AF in diabetic population.

The diabetes epidemic and the increasing number of patients with diabetic chronic vascular complications poses a significant challenge to health care providers. Diabetic kidney disease is a serious diabetes-mediated chronic vascular complication and represents a significant burden for both patients and society in general. Diabetic kidney disease not only represents the major cause of end stage renal disease but is also paralleled by an increase in cardiovascular morbidity and mortality. Any interventions to delay the development and progression of diabetic kidney disease are important to reduce the associated cardiovascular burden. In this review we will discuss five therapeutic tools for the prevention and treatment of diabetic kidney disease: drugs inhibiting the renin-angiotensin-aldosterone system, statins, the more recently recognized sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide 1 agonists, and a novel non-steroidal selective mineralocorticoid receptor antagonist.

Diabetic patients are at higher risk of liver dysfunction compared with the normal population. Thus, using hypoglycemic agents to improve liver efficiency is important in these patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are newly developed antidiabetic drugs with potent glucose-lowering effects. However, recent limited evidence suggests that they have extra-glycemic benefits and may be able to exert protective effects on the liver. Hence, these drugs could serve as promising pharmacological agents with multiple benefits against different hepatic disorders. In this review, the current knowledge about the possible effects of SGLT2 inhibitors on different forms of liver complications and possible underlying mechanisms are discussed.

The principles of treatment for children and adolescents with type 2 diabetes include dietary and exercise management. For dietary management, a relatively modest dietary regimen with an appropriate energy source composition is recommended. Moderate- to vigorous-intensity aerobic activity is recommended for at least 60 min/d. Family members are encouraged to modify their lifestyles. Some patients fail to improve hyperglycemia through dietary and exercise management and eventually require pharmacological treatment. If the patient is metabolically stable (HbA1c level < 8.5% [69 mmol/mol]), metformin is the first-line treatment of first choice. In a case with ketosis or HbA1c of more than 8.5% (69 mmol/mol), insulin will be required initially with once daily basal insulin (0.25-0.5 units/kg). The goal of the initial treatment is to attain an HbA1c level < 7.0% (53 mmol/mol). If the glycemic goal is not attained, the addition of a second agent should be considered. However, the use of antihyperglycemic drugs in pediatric patients is limited in most countries. Therefore, the efficacy and safety of these drugs used in adult patients, including GLP-1 receptor agonists and SGLT2 inhibitors, should be evaluated in pediatric patients worldwide.

Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM.

Diabetes Mellitus is a multifactorial disease with a critical impact worldwide. During prediabetes, the presence of various inflammatory cytokines and oxidative stress will lead to the pathogenesis of type 2 diabetes. Furthermore, insulin resistance and chronic hyperglycemia will lead to micro- and macrovascular complications (cardiovascular disease, heart failure, hypertension, chronic kidney disease, and atherosclerosis). The development through the years of pharmacological options allowed us to reduce the persistence of chronic hyperglycemia and reduce diabetic complications. This review aims to highlight the specific mechanisms with which the new treatments for type 2 diabetes reduce oxidative stress and insulin resistance and improve cardiovascular outcomes.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of newly introduced antidiabetic drugs with potent hypoglycemic effects. Recent evidence suggests that these drugs have extraglycemic impacts and are therefore able to provide additional benefits beyond glucose lowering. Mitochondrial dysfunction is a central facet of many disorders that negatively impacts many tissues and organs, especially in the setting of diabetes. Therefore, it would be hugely beneficial if an antidiabetic drug could also provide mitochondrial benefits to improve cellular function and reduce the risk of diabetic complications. In this review, we have surveyed the literature for possible mitochondrial benefits of SGLT2is and we discuss the possible mechanisms involved.

Epicardial adipose tissue is a layer of adipocytes that physiologically surround the myocardium and play some physiologic roles in normal heart function. However, in pathologic conditions, the epicardial adipose tissue can present a potent cardiac risk factor that is capable of impairing heart function through several pathways, increasing the risk of dysrhythmia and creating an inflammatory milieu around the heart tissues. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a relatively newly introduced class of antidiabetes drugs which effectively normalize blood glucose via overt glycosuria. Some recent reports suggest that these drugs are able to modulate epicardial adiposity and decrease the risk of cardiac complications in diabetic patients who are at higher risk of epicardial adiposity-dependent cardiac disorders. If proven to be true, these antidiabetic drugs can provide dual benefits as both hypoglycemic agents and as epicardial adiposity normalizing agents, thus providing cardiac benefits. In this study, we discuss the physiological and pathophysiological importance of epicardial adiposity and the potential positive effects of SGLT2is in the diabetic milieu.

Clinical trials have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) are closely associated with hepatic fibrosis and steatosis by FibroScan. This paper aimed at evaluating the effects of SGLT2i on hepatic fibrosis and steatosis, which are presented as liver stiffness measurement (LSM) and controlled attenuation parameter (CAP).

PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, and Wanfang Database were searched for randomized clinical trials from database establishment to 30 November 2022 with no language restrictions. The risk of bias was evaluated by Collaboration Handbook. Software Stata 17 and Review Manager (version 5.3) were used for meta-analysis.

A total of eight articles including 686 patients were included. Compared with the control group, our results showed that SGLT2i could lower levels of LSM [MD = -0.82, 95%CI (-1.38, -0.25), p = 0.005] and CAP [MD = -12.80, 95%CI (-20.57, -5.03), p = 0.001]. Further subgroup analyses indicated that SGLT2i presented more advantages on longer treatment duration and more serious steatosis in decreasing LSM. For CAP, SGLT2i exhibited a clear advantage in subgroup analyses of longer treatment duration, younger people, dapagliflozin, worse fibrosis, and steatosis.

SGLT2i could reduce LSM and CAP in contrast to other antihyperglycemic drugs. However, the included studies are not definitive, and well-designed, more multi-centered, blinded randomized clinical trials are warranted to definitively establish reliable evidence.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a newly developed class of highly effective antidiabetic therapies that normalize hyperglycemia via urinary glucose excretion. However, they may be accompanied by certain side effects that negatively impact their therapeutic benefits. SGLT2is induce a metabolic shift from glucose to fatty acids and thus increase lipolysis which, in turn, induces ketogenesis. The complete pathways linking SGLT2is to ketoacidosis have not yet been fully elucidated, though much is now known. Therefore, in this mechanistic study, we present the current knowledge and shed light upon the possible cellular pathways involved. A deeper understanding of the possible links between SGLT2is and ketogenesis could help to prevent adverse side effects in diabetic patients treated with these drugs.

Chronic hyperglycemia induces pathophysiologic pathways with negative effects on the metabolism of most substrates as well as lipids and lipoproteins, and thereby induces dyslipidemia. Thus, the diabetic milieu is commonly accompanied by different levels of atherogenic dyslipidemia, which is per se a major risk factor for subsequent complications such as atherosclerosis, coronary heart disease, acute myocardial infarction, ischemic stroke, and nephropathy. Therefore, readjusting lipid metabolism in the diabetic milieu is a major goal for preventing dyslipidemia-induced complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of relatively newly introduced antidiabetes drugs (including empagliflozin, canagliflozin, dapagliflozin, etc.) with potent hypoglycemic effects and can reduce blood glucose by inducing glycosuria. However, recent evidence suggests that they could also provide extra-glycemic benefits in lipid metabolism. It seems that they can increase fat burning and lipolysis, normalizing the lipid metabolism and preventing or improving dyslipidemia. Nevertheless, the exact mechanisms involved in this process are not well-understood. In this review, we tried to explain how these drugs could regulate lipid homeostasis and we presented the possible involved cellular pathways supported by clinical evidence.

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.

Sodium-glucose transport protein 2 inhibitors, commonly referred to as SGLT2i, are a group of prescription pharmaceuticals that are approved by the United States Food and Drug Administration for use with diet and exercise to lower blood glucose in adults with type 2 diabetes. Diabetes is a well-recognized major contributor to cardiovascular and renal disease burden. In addition to blood glucose control, SGLT2i have been shown to provide significant cardiovascular and renoprotective benefits in patients with and without diabetes. In this review, we describe current evidence related to the renal and cardiovascular benefits of using SGLT2i.

Alteration of the hydration status with the use of sodium-glucose co-transporter- 2 inhibitors (SGLT2i) during the Holy Ramadan has not been studied in depth. Precisely, we aimed to detect the potential alteration of hydration status in adult Muslims with type 2 diabetes mellitus (T2D) who used SGLT2i during Ramadan.

An observational non-interventional study included 245 patients with type 2 diabetes mellitus of matched age and sex. The study included 3 groups: empagliflozin group; 87 patients, dapagliflozin group; 85 patients and control group; 73 patients without the use of SGLT2i. Participants in each group were well-settled on their medications for more than 3 months before the onset of Ramadan. Clinical and biochemical parameters of hydration status were evaluated during the last week of Ramadan.

We noticed a higher prevalence of orthostatic dizziness and postural hypotension among SGLT2i users than non-SGLT2i users (p < 0.001). The mean arterial blood pressure was significantly lowered among users of empagliflozin and dapagliflozin than non-SGLT2i users; 93.7 ± 5.1 and 93.1 ± 6.9 versus 106.2 ± 4.3, p < 0.001, respectively. Moreover, patients who used empagliflozin or dapagliflozin exhibited significantly higher values of urine specific gravity; 1029.6 ± 1.5 and 1029.1 ± 1.6 versus 1016.9 ± 4.4, p < 0.001, serum osmolality; 300.7 ± 10.2 and 297.8 ± 8.9 versus 290.9 ± 6.7, p < 0.001, and BUN/creatinine ratio; 24.1 ± 4.1 and 23.2 ± 4.6 versus 16.3 ± 4.2, p < 0.001 than non-SGLT2i users.

Significant clinical and biochemical markers of dehydration were noticed among users of SGLT2i during the Holy Ramadan.

Many patients with diabetes mellitus, especially those with chronic kidney disorders, have some degree of anemia due to a spectrum of causes and underlying pathophysiologic pathways. As such, enhancement in erythropoiesis is important in these patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs with confirmed protective effects in kidney and cardiovascular tissues. Recent evidence suggests that these drugs may provide additional benefits in enhancing hematopoietic processes in diabetic patients. Though the exact mediating pathways have not been fully elucidated, cellular mechanisms are likely involved. In the current study, we present the potential pathways by which SGLT2i may modulate hematopoiesis and stimulate erythropoiesis.