Search

Objective: Diabetes-related care makes up approximately 24% of outpatient clinic visits. Therefore, confidence and understanding of diabetes management is necessary for family medicine residents. Methods: We developed a combined lecture and simulation lab curriculum utilizing a registered nurse and pharmacist to deliver education to 20 family medicine learners. Pre and post surveys of the educational material were completed in 2 sections including one gauging medical knowledge and a second part gauging level of comfort. Results: Of the learners who participated, fourteen completed the pre-post surveys. Most (53%) respondents improved their scores, while 20% scored the same 27% scored worse. The overall average score increased 57% to 70% and improvement was statistically significant (P <.05). All learners improved confidence by at least 1 point. Conclusion: An interprofessional team utilizing a lecture curriculum focusing on providing education on effective prescribing, medication safety profiles, and resource availability, showed improvement in confidence but mixed knowledge benefit. Further modifications to the curriculum may yield further educational gains. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Germany that examines the relationship between regional socioeconomic factors and the use of certain medications for adults with type 2 diabetes. The study finds that individuals in socioeconomically disadvantaged areas have lower access to newer glucose-lowering medications, such as SGLT2 inhibitors and GLP-1RAs. This disparity in access may contribute to socioeconomic disparities in cardiovascular health outcomes. The study suggests that further investigation into structural factors is needed to address these disparities. The study also highlights the importance of raising awareness among healthcare providers and overcoming barriers to access for newer treatment options in order to reduce inequalities. [Extracted from the article]

Objective: This study aimed to assess the effects of sodium-glucose co-transporter inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) on individuals subjected to diabetes and COVID-19. Methods: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched to cover studies (except for case reports and review studies) published until August 30, 2022. The primary outcome was the mortality of people with diabetes and COVID-19. The secondary outcomes comprised the requiring intensive care unit (ICU) admission and mechanical ventilation. Two reviewers independently screened studies, abstracted data, and assessed risk-of-bias. Furthermore, the network meta-analyses (NMA) were conducted. Results: A total of 12 trials were involved in the analysis. The OR and 95% CI of mortality for SGLT2i compared with SGLT2i + GLP-1RA and DPP4i reached 0.41 (0.17,0.97) and 0.69 (0.49,0.98), respectively. The OR and 95% CI of requiring mechanical ventilation for SGLT2i compared with the DPP4i reached 0.85 (0.75,0.97). Conclusions: As revealed by the result of this study, SGLT2i is associated with the lower mortality rate in people with diabetes and COVID-19 among novel glucose-lowering drugs. And SGLT2i is linked to lower requiring mechanical ventilation. These findings can have a large impact on clinicians' decisions amid the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Limited direct comparative studies exist in terms of the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on the kidney outcomes in Japanese individuals with type 2 diabetes. Methods: This retrospective cohort study included 561 Japanese adults with type 2 diabetes, who were newly prescribed either an SGLT2i or a DPP4i and had an eGFR ≥ 30 mL/min/1.73 m2. The cohort comprised 207 women and 354 men, with a mean (± standard deviation) age of 63 (± 12) years. The exposure and outcome were SGLT2i or DPP4i initiation and eGFR slope during the overall follow-up period, restricted to participants who were followed for ≥2 years. We adopted the on-treatment analysis. Analysis of covariance was used to compare the adjusted eGFR slope between the two groups, incorporating 10 variables at baseline. Results: During the median follow-up period of 3.4 years, least square mean (95% CI) eGFR slopes were −1.91 (−2.15, −1.67) and −1.12 (−1.58, −0.67) mL/min/1.73 m2/year in individuals treated with a DPP4i (n = 460) and an SGLT2i (n = 101), respectively, demonstrating statistical significance (p = 0.002). The robustness of this finding was strengthened by sensitivity analyses. Conclusions: This study provides potential evidence of the superiority of SGLT2is over DPP4is in slowing kidney function decline in Japanese adults with type 2 diabetes and eGFR ≥ 30 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure. Objective: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function. Methods: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader. Results: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m2, minimum LA volume 11.1 ± 5.7mL/m2) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m2, minimum LA volume 12.6 ± 5.0mL/m2) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m2 (95% CI: -1.7 to 3.7 mL/m2; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m2 (95% CI: -0.9 to 2.6 mL/m2; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference − 0.01 (95% CI: -0.05 to 0.03, p = 0.59). Conclusion: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970). [ABSTRACT FROM AUTHOR]

Background Pre–diabetes mellitus (DM) is associated with proteinuria, a risk factor for chronic kidney disease. While people with human immunodeficiency virus (HIV; PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among prediabetic persons. Methods The urine protein-to-creatinine ratio was measured at semiannual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of antidiabetic medications were included. Pre-DM was defined as a fasting glucose level of 100–125 mg/dL confirmed within a year by a repeated fasting glucose or hemoglobin A1c measurement of 5.7%–6.4%. Incident proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) >200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-DM differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. Results Between 2006 and 2019, among 1276 men with pre-DM, proteinuria developed in 128 of 613 PWH (21%) and 50 of 663 PWOH (8%) over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-DM was 3.3 times (95% confidence interval, 2.3–4.8 times) greater than in PWOH (P <.01). Among PWH, current CD4 cell count <50/µL (P <.01) and current use of protease inhibitors (P =.03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. Conclusions Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population. [ABSTRACT FROM AUTHOR]

The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation. [ABSTRACT FROM AUTHOR]

The key aim of diabetes management is to prevent complications, which are a major cause of morbidity and mortality. At an individual level, people with diabetes are less likely than they were several decades ago to experience classical macrovascular and microvascular complications as a result of improvements in modifiable cardiovascular risk factors and preventive healthcare. However, a significant burden of diabetes complications persists at a population level because of the increasing incidence of diabetes, as well as longer lifetime exposure to diabetes because of younger diagnosis and increased life expectancy. Trials have shown that the most effective strategy for preventing complications of diabetes is a multifactorial approach focussing simultaneously on the management of diet, exercise, glucose levels, blood pressure and lipids. In addition to the cornerstone strategies of addressing diet, exercise and lifestyle measures, the introduction of newer glucose‐lowering agents, including sodium‐glucose transport protein 2 inhibitors and glucagon‐like peptide‐1 agonists, have brought about a paradigm shift in preventing the onset and progression of complications of type 2 diabetes, particularly cardiovascular and renal disease. The improvement in rates of classical complications of diabetes over time has been accompanied by a growing awareness of non‐traditional complications, including non‐alcoholic fatty liver disease. These emerging complications may not respond to a glycaemic‐centred approach alone and highlight the importance of foundational strategies centred on lifestyle measures and supported by pharmaceutical therapy to achieve weight loss and reduce metabolic risk in patients living with diabetes. [ABSTRACT FROM AUTHOR]

Progression to symptomatic heart failure is a complication of type 2 diabetes; heart failure onset in this setting is commonly preceded by deterioration in exercise capacity. This study sought to determine whether AT-001, a highly selective aldose reductase inhibitor, can stabilize exercise capacity among individuals with diabetic cardiomyopathy (DbCM) and reduced peak oxygen uptake (V o 2). A total of 691 individuals with DbCM meeting inclusion and exclusion criteria were randomized to receive placebo or ascending doses of AT-001 twice daily. Stratification at inclusion included region of enrollment, cardiopulmonary exercise test results, and use of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists. The primary endpoint was proportional change in peak V o 2 from baseline to 15 months. Subgroup analyses included measures of disease severity and stratification variables. The mean age was 67.5 ± 7.2 years, and 50.4% of participants were women. By 15 months, peak V o 2 fell in the placebo-treated patients by −0.31 mL/kg/min (P = 0.005 compared to baseline), whereas in those receiving high-dose AT-001, peak V o 2 fell by −0.01 mL/kg/min (P = 0.21); the difference in peak V o 2 between placebo and high-dose AT-001 was 0.30 (P = 0.19). In prespecified subgroup analyses among those not receiving sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists at baseline, the difference between peak V o 2 in placebo vs high-dose AT-001 at 15 months was 0.62 mL/kg/min (P = 0.04; interaction P = 0.10). Among individuals with DbCM and impaired exercise capacity, treatment with AT-001 for 15 months did not result in significantly better exercise capacity compared with placebo. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy [ARISE-HF]; NCT04083339) [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose‐lowering therapy (GLT) in this population is uncertain. Methods and results: DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre‐specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow‐up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50–1.00; 1 GLT: HR 1.04, 95% CI 0.80–1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56–0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59–0.92) and without background metformin use (HR 0.89, 95% CI 0.72–1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69–1.16) and without background insulin use (HR 0.78, 95% CI 0.65–0.95; pinteraction = 0.45). Dapagliflozin was well‐tolerated irrespective of the number of background GLTs. Conclusions: Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF >40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first‐line SGLT2i among individuals with T2D and HF, irrespective of background GLT. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β‐cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis. [ABSTRACT FROM AUTHOR]

Background: Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19. Methods: We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications. Results: 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58–0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59–0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69–0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26–1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50–0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76–0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62–0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81–0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79–0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12–1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography. Conclusion: Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies. [ABSTRACT FROM AUTHOR]

Copyright of Annales Françaises de Médecine d'Urgence is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Heart failure (HF) is a complex clinical syndrome caused by structural or functional dysfunction of the ventricular filling or blood supply. Diabetes mellitus (DM) is an independent predictor of mortality for HF. The increase in prevalence, co-morbidity and hospitalization rates of both DM and HF has further fueled the possibility of overlapping disease pathology between the two. For decades, antidiabetic drugs that are known to definitively increase the risk of HF are the thiazolidinediones (TZDs) and saxagliptin in the dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin, which causes sodium and water retention, and whether metformin is effective or safe for HF is not clear. Notably, sodium-glucose transporter 2 (SGLT2) inhibitors and partial glucagon-like peptide-1 receptor agonists (GLP-1 RA) all achieved positive results for HF endpoints, with SGLT2 inhibitors in particular significantly reducing the composite endpoint of cardiovascular mortality and hospitalization for heart failure (HHF). Further understanding of the mutual pathophysiological mechanisms between HF and DM may facilitate the detection of novel therapeutic targets to improve the clinical outcome. This review focuses on the association between HF and DM, emphasizing the efficacy and safety of antidiabetic drugs and HF treatment. In addition, recent therapeutic advances in HF and the important mechanisms by which SGLT2 inhibitors/mineralocorticoid receptor antagonist (MRA)/vericiguat contribute to the benefits of HF are summarized. [ABSTRACT FROM AUTHOR]

Introduction: Cholesteryl ester transfer protein (CETP) inhibitors, initially developed for treating hyperlipidemia, have shown promise in reducing the risk of new-onset diabetes during clinical trials. This positions CETP inhibitors as potential candidates for repurposing in metabolic disease treatment. Given their oral administration, they could complement existing oral medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors, potentially delaying the need for injectable therapies such as insulin. Methods: We conducted a 2x2 factorial Mendelian Randomization analysis involving 233,765 participants from the UK Biobank. This study aimed to evaluate whether simultaneous genetic inhibition of CETP and SGLT2 enhances glycemic control compared to inhibiting each separately. Results: Our findings indicate that dual genetic inhibition of CETP and SGLT2 significantly reduces glycated hemoglobin levels compared to controls and single-agent inhibition. Additionally, the combined inhibition is linked to a lower incidence of diabetes compared to both the control group and SGLT2 inhibition alone. Discussion: These results suggest that combining CETP and SGLT2 inhibitor therapies may offer superior glycemic control over SGLT2 inhibitors alone. Future clinical trials should investigate the potential of repurposing CETP inhibitors for metabolic disease treatment, providing an oral therapeutic option that could benefit high-risk patients before they require injectable therapies like insulin or glucagon-like peptide-1 (GLP-1) receptor agonists. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT-2) are a new class of hypoglycemic drugs that were initially approved for the treatment of type 2 diabetes. Currently, 5 drugs in the SGLT-2 class of drugs are approved by the FDA for glycemic control: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin and sotagliflozin. However, their effectiveness in reducing the risk of heart failure and progression of chronic kidney disease was soon established, regardless of diabetes status. In addition, according to a number of meta-analyses of RCTs in patients with cardiometabolic and renal diseases, the use of SGLT-2 reduces cardiovascular and overall mortality and the number of serious adverse cardiac events and renal outcomes in patients with or without diabetes, which is reflected in the indications to their use. Scientific data are presented in a discussion of the mechanisms of cardioprotective and renoprotective effects of the SGLT-2 class, many of which are considered as pleiotropic effects not related to the effect on glycemic levels.

Background: The incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs. Methods: We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn's disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control. Results: Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10− 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10− 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10− 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10− 2). Conclusions: The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Aim: To compare the risk of developing kidney outcomes with use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) versus use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors among individuals with diabetes. Materials and Methods: In this retrospective observational study, we analysed 12 338 individuals with diabetes who newly initiated SGLT2 inhibitors or GLP‐1RAs using data from the JMDC claims database. The primary outcome was change in the estimated glomerular filtration rate (eGFR), estimated using a linear mixed‐effects model. A 1:4 propensity‐score‐matching algorithm was used to compare the changes in eGFR between GLP‐1RA and SGLT2 inhibitor users. Results: After propensity‐score matching, 2549 individuals (median [range] age 52 [46–58] years, 80.6% men) were analysed (510 GLP‐1RA new users and 2039 SGLT2 inhibitor new users). SGLT2 inhibitor use was associated with a slower eGFR decline when compared with GLP‐1RA use (−1.41 [95% confidence interval −1.63 to −1.19] mL/min/1.73 m2 vs. −2.62 [95% confidence interval −3.15 to −2.10] mL/min/1.73 m2). Conclusions: Our analysis demonstrates the potential advantages of SGLT2 inhibitors over GLP‐1RAs in terms of kidney outcomes in individuals with diabetes. [ABSTRACT FROM AUTHOR]

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]

Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium–glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the efficacy of incorporating a combination of SGLT2 inhibitors (SGLT2i) and thiazolidinediones (TZD) into the current triple therapy regimen (metformin+sulphonylurea+DPP4 inhibitors) for individuals with diabetes. The primary objective was to compare the outcomes of the active group, which received the supplementary treatment, with the control group, which followed the standard triple regimen without additional medications. Methods: Participants were allocated into two groups: the active group and the control group. The active group received SGLT2i and TZD in addition to their existing triple therapy, while the control group continued with the standard triple regimen. Various clinical parameters including blood pressure, glycemic control, and lipid profiles were assessed and compared between the two groups. Results: The active group demonstrated significant improvements in multiple clinical parameters. Notably, there were reductions in systolic blood pressure, diastolic blood pressure, HbA1c levels, and total cholesterol levels. In contrast, the control group showed more modest improvements in HbA1c levels and total cholesterol levels, but not as significant as those observed in the active group. The active group exhibited superior outcomes in terms of glycemic control, blood pressure control, and lipid profiles compared to the control group. Conclusion: The incorporation of SGLT2i and TZD into the preexisting triple therapy regimen resulted in notable enhancements in glycemic regulation, blood pressure, and lipid profiles in individuals with diabetes. These findings support the potential benefits of adding SGLT2i and TZD as adjunct therapies in diabetes management. However, further research with larger sample sizes and longer follow-up periods is needed to validate these findings and evaluate the long-term impacts and safety characteristics of this combined treatment approach. [ABSTRACT FROM AUTHOR]

Velagliflozin is the active ingredient of the first oral liquid medication approved by the Food and Drug Administration for the treatment of diabetes in cats. This compound belongs to the known class of sodium-glucose cotransporter 2 inhibitors approved to treat diabetes in human. Here, we report the detailed synthesis of velagliflozin labeled with carbon 14 and carbon 13. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have cardiovascular benefits in type 2 diabetes, but none of the cardiovascular trials studied atrial fibrillation/atrial flutter (AF) as a primary endpoint. Data from post-marketing surveillance studies remains sparse. Objective: To examine the real-world risk of AF comparing GLP-1RA with other non-insulin glucose-lowering agents. Design: Cohort study using de-identified electronic health record data from the Optum Labs Data Warehouse. Participants: Adult patients with diabetes who were newly prescribed add-on non-insulin glucose-lowering agents and were on metformin between 2005-2020. Exposures: New users of GLP-1RA were separately compared with new users of dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), using 1:1 propensity score matching to adjust for differences in patient characteristics. Main Measures: The primary outcome was incident AF, defined and captured by diagnosis code for AF. Incidence rate difference (IRD) and hazard ratio (HR) were estimated in the matched cohorts. Key Results: In the matched cohort of 14,566 pairs of GLP-1RA and DPP4i followed for a median of 3.8 years, GLP-1RA use was associated with a lower risk of AF (IRD, -1.0; 95% CI, -1.8 to -0.2 per 1000 person-years; HR, 0.82; 95% CI, 0.70 to 0.96). In the matched cohort of 9,424 pairs of patients on GLP-1RA and SGLT2i with a median follow-up of 2.9 years, there was no difference in the risk for AF (IRD, 0.4; 95% CI -0.7 to 1.5 per 1000 person-years; HR, 1.12; 95% CI, 0.89 to 1.42). Conclusions: In this real-word study, GLP-1RA was associated with a lower risk of AF compared with DPP4i, but no difference compared with SGLT2i, suggesting that cardiovascular benefits of GLP-1RA use may extend to prevention for AF in patients with diabetes. Our findings call for future randomized controlled trials to focus on the effects of GLP-1RA on AF prevention. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium‐glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. Methods: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non‐SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression‐free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. Results: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non‐SGLT2i cohort. Compared to non‐SGLT2i recipients, SGLT2i recipients had a higher rate of 5‐year OS (86.2% [95% CI: 72.0–93.5] vs 62.3% [95% CI: 50.9–71.8], P = 0.013) and 5‐year PFS (76.6% [95% CI: 60.7–86.7] vs 57.0% [95% CI: 46.2–66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50–70% reduction in all‐cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. Conclusion: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Hyperglycemia in acute stroke patients worsens neurological outcomes. However, effective and safe management during the acute stage has not been established. Therefore, we aimed to compare the effect of medications and nutrition therapy on blood glucose control in three cohorts with different carbohydrate content and availability of sodium-glucose cotransporter 2 inhibitors (SGLT2is) to identify the current optimal treatment for acute-stage hyperglycemia. We retrospectively studied patients with acute stroke admitted to our hospital between 2011 and 2019. We divided the study period into three periods as follows: traditional (Td, 2011-2013), transition (Ts, 2013-2014), and novel (N, 2014-2019). To evaluate glucose-lowering efficacy and safety, we included conscious patients with glycated hemoglobin A1c =6.5%, blood glucose levels =11.1 mmol/L, normal renal function at admission, oral diet and medications, and fasting blood glucose (FBG) test on day 7. We performed total energy restriction (TER) in each period with different carbohydrate contents: 60% in Td, 40% in Ts, and N. The attending physicians chose glucose-lowering medications. SGLT2is were available in the N period only. Our target FBG was<7 mmol/L by day 7. The 26, 22 and 36 patients were enrolled in the Td, Ts and N periods. The blood glucose levels significantly decreased by day 7 in all periods. The target FBG was achieved in 30.8% of Td patients, 31.8% of Ts patients, and 72.2% of N patients. The N period had the highest population of achieving the target FBG. The 40%-carbohydrate diet based on TER plus SGLT2is was the most effective way to lower blood glucose levels. The N period had the highest population of positive urine ketones. However, no symptomatic ketoacidosis occurred. A 40%-carbohydrate diet based on TER combined with SGLT2is might be a potentially effective and safe treatment for hyperglycemia in acute stroke-conscious patients. [ABSTRACT FROM AUTHOR]

Objective: To review the pharmacology of bexagliflozin in addition to its safety and efficacy from available clinical trials used for its approval, as well as available clinical evidence to date. Data Sources: A search of the National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) and PubMed database was performed from inception through June 1, 2023. Study Selection and Data Extraction Quantification: The following study designs were included: meta-analyses, systematic review, clinical trial, or observational study design. Abstracts and drug monographs were also reviewed. Narrative or scoping reviews were excluded. Only articles in the English language and those evaluating the pharmacology, pharmacokinetics, safety, or efficacy of bexaglifozin in humans were included. Data Synthesis: Bexagliflozin reduces hemoglobin A1c ~0.5% with similar reductions in systolic blood pressure and body weight to other SGLT2 inhibitors. No cardiovascular outcomes trial is published, nor ongoing at this time. Adverse effects are similar to other SGLT2 inhibitors (genital mycotic and urinary tract infections, increased urination) including a warning for lower extremity amputation similar to canagliflozin. Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Although no cost-effectiveness data are available, statements from the manufacturer suggest a competitive price point. Given limited trial data, lower cost, if chosen, may create a temporary niche for bexagliflozin pending generic availability of other SGLT2 inhibitors. However, given lack of cardiovascular and renal outcome data, empagliflozin, dapagliflozin, or canagliflozin may be preferred. Conclusion: Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with preserved ejection fraction (HFpEF). Data sources: A literature search of PubMed, the Cochrane Library, and Google Scholar databases (January 2015 to June 20, 2023) was performed with keywords: sodium-glucose co-transporter 2 inhibitors OR SGLT2 inhibitors OR bexagliflozin OR canagliflozin OR dapagliflozin OR empagliflozin OR ertugliflozin OR sotagliflozin AND heart failure OR heart failure with preserved ejection fraction, and terms related to CV outcomes including cardiovascular death, hospitalization, hospitalization for heart failure, mortality, death, and major adverse cardiovascular event (MACE). Study selection and data extraction: The reference list from retrieved articles as well as relevant review articles was considered. Pivotal randomized controlled trials and meta-analyses with a primary or secondary end point of CV death or heart failure hospitalization were included. Studies conducted solely in a diabetic patient population were excluded. Data synthesis: Dapagliflozin and empagliflozin, in a broad population of heart failure patients including, HFrEF, HFmrEF, HFpEF, and without diabetes, have shown consistent improvement in the combined outcome of CV death and hospitalization for heart failure (HR 0.80, 95% CI 0.73-0.87) and in the reduction of heart failure hospitalizations (HR 0.74, 95% CI 0.67-0.83). In patients with HFpEF, cardiovascular mortality was not demonstrated (HR 0.88, 95% CI 0.77-1.00). Rates of adverse events were low. Relevance to patient care and clinical practice: Patients with HFpEF and NYHA class II-III with frequent symptoms or hospitalizations for heart failure derive the most benefit from SGLT2 inhibitors with an overall goal of a reduction in heart failure hospitalizations. Conclusions: The treatment of HFpEF has made progress, but there is still work to be done. Now, SGLT2 inhibitor therapy can be used to further help with symptom control and reduce overall hospitalizations for heart failure. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease. [Display omitted] • Treatment with SGLT2is is associated with an increased risk of GMI but not UTI or necrotizing fasciitis of the perineum (Fournier's gangrene). • The benefits of SGLT2is usually outweigh the risk of treatment-associated GU infections. • In most cases, patients developing mild-moderate or stable severe GU infections can continue SGLT2is. [ABSTRACT FROM AUTHOR]

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. Sodiumglucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extraglycemic 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. [ABSTRACT FROM AUTHOR]

An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed. [ABSTRACT FROM AUTHOR]

Background: Large cardiovascular outcomes trials in individuals with heart failure, with and without diabetes, have demonstrated a significant risk reduction in the composite outcome of cardiovascular death or hospitalizations for heart failure with SGLT2 inhibitor therapy. These positive outcomes have led to the recommendation that SGLT2 inhibitors serve as backbone therapy in patients with heart failure reduced ejection fraction (HFrEF). To date, there has not been enough participants in clinical trials on concomitant SGLT2 inhibitor and angiotensin receptor-neprilysin inhibitor therapy to evaluate the benefits and risks of combination therapy with these two agents outside of smaller subgroup analyses. Case Summary: This case describes a Black female with diabetes meeting her glycemic targets and concomitant stable NYHA FC II HFrEF on guideline-directed medical therapy (GDMT) with sacubitril/valsartan, spironolactone and metoprolol succinate who developed severe hypotension and dehydration requiring hospitalization after initiation of SGLT2 inhibitor therapy. Practice Implications: This case report raises the question of whether those with type 2 diabetes, and/or those on background angiotensin receptor-neprilysin inhibitor therapy, who are euvolemic or sensitive to diuretic therapy should be started on lower dose dapagliflozin and titrated to 10 mg daily based on response. It also raises awareness to the potential increased diuretic effect produced with concomitant use of sacubitril/valsartan and dapagliflozin. Caution and education to mitigate the risk for volume depletion should be provided to those patients who are euvolemic and initiated on a SGLT2 inhibitor, regardless of their background diuretic and GDMT. Conclusion: Future research should focus on the benefits and safety considerations and provide education on how to best initiate and adjust SGLT2 inhibitors in the setting of sacubitril/valsartan use in diverse heart failure patient populations. [ABSTRACT FROM AUTHOR]

Objective: To determine whether Glucagon-Like Peptide 1 (GLP-1) agonists or Sodium Glucose Transporter 2 (SGLT-2) inhibitors result in greater A1c reduction, weight loss, and reduction of insulin requirements in veterans using multiple daily doses of insulin. Methods: This retrospective, single-site, cohort study included patients of VA Eastern Kansas Health Care System with a diagnosis of Type II Diabetes utilizing multiple daily dose insulin and an SGLT-2 inhibitor or GLP-1 agonist. SAS Enterprise Guide was utilized to complete a multivariate analysis of variance to evaluate all outcomes. Key Findings: 150 patients met selection criteria. The GLP-1 group averaged a.65% reduction in A1c compared to a 1.05% reduction in the SGLT-2 group (P =.1397). The Basal insulin dose was reduced by 5.5 units in the GLP-1 group vs 2.45 units in the SGLT-2 group (P =.3132), and 7.12 units vs 8.14 units respectively for short-acting insulin (P =.8170). The resulting weight reduction was 4.1 Kg in the GLP-1 group compared to 3.6 Kg in the SGLT-2 group (P =.6993). Conclusion: The results suggest there is not a statistically significant difference in changes to A1c, insulin requirements, or weight after 1 year of treatment with an SGLT-2 vs GLP-1 in patients using multiple daily insulin injections. [ABSTRACT FROM AUTHOR]

Simple Summary: Diabetes is an important risk factor for the development of pancreatic cancer due to the production of cytokines that cause increased cell proliferation. In this review, we have explored the effects of SGLT2 inhibitors, GLP-1 RA, DPP-4 inhibitors, and metformin on the risk of developing pancreatic cancer. Our review shows that some antidiabetic drugs may have a role in decreasing the risk of pancreatic cancer through different mechanisms. We have described their immunomodulatory roles, safety profiles, and association with pancreatic cancer. Pancreatic carcinoma is a highly aggressive tumor that usually presents when it has already metastasized. Therapeutic options for cure remain scarce and rely on combination chemotherapy with limited sustainability. Diabetes is considered an important risk factor for the development of pancreatic cancer due to the production of proinflammatory cytokines, which result in increased cell proliferation. More than half of patients diagnosed with pancreatic cancer eventually develop diabetes due to the destruction of insulin-producing cells. The interlinkage of both diseases might identify a possible preventative strategy for reducing the incidence of pancreatic carcinoma. This study reviewed the recent literature on the association between pancreatic cancer risk and SGLT2 inhibitors, GLP-1 RA, DPP-4 inhibitors, and biguanides. There are mixed data regarding the relationship between GLP-1 RA and DPP-4 inhibitors and pancreatic cancer, with some trials suggesting that they might increase the risk. In contrast, studies have mostly revealed that SGLT2 inhibitors have an antiproliferative effect on various tumors, such as liver, pancreatic, prostate, bowel, lung, and breast carcinoma, which might be due to their mechanism of blockage of reabsorption of glucose by cells, lowering the amount of available glucose for the growth of tumor cells. Metformin, the first-line agent for diabetes, has also been shown to be associated with decreasing pancreatic cancer risk and improving prognosis in those who already have the disease. Dedicated trials are needed to further delineate the association of antidiabetic drugs with the risk of pancreatic cancer in the general population, as previous studies have mostly focused on diabetic patients. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) and liver cirrhosis are clinical entities that frequently coexist, but glucose‐lowering medication options are limited in cirrhotic patients. Sodium–glucose linked transporter 2 (SGLT2) inhibitors are a class of glucose‐lowering medication that act independently of insulin, by causing glycosuria in the proximal convoluted tubule. In this review, we aimed to briefly present the main data and to provide insight into the pathophysiology and potential usefulness of SGLT2 inhibitors in cirrhotic patients with or without T2DM. SGLT2 inhibitors have been proven useful as antidiabetic treatment in patients with metabolic liver disease, with most robust data from patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), where they also showed improvement in liver function parameters. Moreover, it has been suggested that SGLT2 inhibitors may have effects beyond their antidiabetic action. Accordingly, they have exhibited cardioprotective effects, expanding their indication in patients with heart failure without T2DM. Since decompensated liver cirrhosis and congestive heart failure share common pathophysiological features, namely renin–angiotensin–aldosterone axis and sympathetic nervous system activation as well as vasopressin secretion, SGLT2 inhibitors could also be beneficial in patients with decompensated cirrhosis, even in the absence of T2DM. [ABSTRACT FROM AUTHOR]

Background: Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) are now indicated for heart failure and chronic kidney disease (CKD), irrespective of the presence of diabetes. Hence, cardiologists and nephrologists have an important role in initiating these drugs. Aims: To explore cardiologists' and nephrologists' perspectives regarding initiating SGLT2i and their safety monitoring practices when initiating SGLT2i. Methods: Purposive and snowball approaches were used to recruit participants working in diverse areas in New South Wales, Australia. Semi‐structured interviews were conducted with 12 cardiologists and 12 nephrologists. Interviews were conducted until thematic saturation was reached. Emergent themes were identified from transcripts. An iterative general inductive approach was used for data analysis. Results: There was a reluctance amongst most non‐heart‐failure subspecialist cardiologists to initiate SGLT2i. Reasons included the perception of SGLT2i as diabetes drugs, concern about side effects, lack of experience and issues with follow‐up. In contrast, nephrologists reported feeling confident to initiate SGLT2i. Nephrologists varied in their opinions about the severity of CKD at which SGLT2i initiation was reasonable and monitoring of renal function following initiation. Government subsidisation was an important factor in the decision to prescribe SGLT2i to people without diabetes. Conclusions: Our findings highlight the complex transition from the perception of SGLT2i as diabetes drugs to cardiometabolic and reno‐protective agents. Interdisciplinary collaboration may enable greater confidence amongst specialists to initiate SGLT2i, including in patients with CKD. Additionally, there is a need for clear and detailed guidance about SGLT2i prescription in patients with renal dysfunction and renal function monitoring following SGLT2i initiation. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is an increasingly common long-term condition, and suboptimal perioperative glycaemic control can lead to postoperative harms. The advent of new antidiabetic drugs, in particular glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, has enabled perioperative continuation of these medicines, thus avoiding the harms of variable rate i.v. insulin infusions whilst providing glycaemic control. There are differences between medicines regulatory agencies and organisations on how these classes that are most often used to treat diabetes mellitus, (but also in the case of SGLT2 inhibitors chronic kidney disease and heart failure in those without diabetes) should be managed in the perioperative period. In this commentary, we argue that GLP-1 receptor agonists should continue during the perioperative period and that SGLT2 inhibitors should only be omitted the day prior to a planned procedure. The reasons for the differing advice advocated between regulatory agencies and what anaesthetic practitioners should do in the face of continuing uncertainty are discussed. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel oral anti-hyperglycemic drugs that demonstrate cardiovascular and metabolic benefits for patients with type 2 diabetes (T2D), heart failure (HF), and chronic kidney disease (CKD). There is limited knowledge of real-world data to predict adherence to SGLT-2i in an ambulatory setting. The study aims to predict SGLT-2i adherence in patients with T2D and/or HF and/or CKD by building a prediction model using electronic prescription claims data presented within EPIC datasets. This is a retrospective study of 174 adult patients prescribed SGLT-2i at UC San Diego Health ambulatory pharmacies between 1 January 2020 to 30 April 2021. Adherence was measured by the proportion of days covered (PDC). R packages were used to identify regression and non-linear regression predictive models to predict adherence. Age, gender, race/ethnicity, hemoglobin A1c, and insurance plan were included in the model. Diabetes control based on hemoglobin A1c (HbA1c) and the glomerular filtration rate (GFR) was also evaluated using Welch t-test with a p-value of 0.05. The best predictive model for measuring adherence was the simple decision tree. It had the highest area under the curve (AUC) of 74% and accuracy of 82%. The model accounted for 21 variables with the main node predictors, including glycated hemoglobin, age, gender, and insurance plan payment amount. The adherence rate was inversely proportional to HbA1c and directly proportional to the plan payment amount. As for secondary outcomes, HbA1c values from baseline till 90 days post-treatment duration were consistently higher in the non-compliant group: 7.4% vs. 9.6%, p < 0.001 for the PDC ≥ 0.80 and PDC < 0.80, respectively. Baseline eGFR was 55.18 mL/min/1.73m2 vs. 54.23 mL/min/m2 at 90 days. The mean eGFR at the end of the study (minimum of 90 days of treatment) was statistically different between the groups: 53.1 vs. 59.6 mL/min/1.73 m2, p < 0.001 for the PDC ≥ 0.80 and PDC < 0.80, respectively. Adherence predictive models will help clinicians to tailor regimens based on non-adherence risk scores. [ABSTRACT FROM AUTHOR]

The article explores the efficacy of SGLT-2 inhibitors and GLP-1 receptor agonists in treating Type 2 diabetes, highlighting their benefits in reducing mortality, heart attacks, and end-stage kidney disease while also noting increased adverse events. Topics include the comparative benefits and risks of these medications, their impact on weight loss, and comparisons with metformin in terms of efficacy and side effects.

This letter, published in the Journal of General Internal Medicine, discusses a nationwide cohort study on adults with type 2 diabetes mellitus (T2DM) who were receiving an SGLT2 inhibitor. The study found that new users of SGLT2 inhibitors experienced a significant increase in hemoglobin levels compared to those receiving a different medication. The authors suggest that clinicians should be aware of this effect and further studies should be conducted to evaluate its clinical significance. The letter also provides statistical data on the use of insulin treatment and the prevalence of various health conditions in patients with diabetes. The authors disclose their funding sources and potential conflicts of interest, and note that the data used in the study is not available for sharing due to Danish law. [Extracted from the article]

The article focuses on evaluating the safety and efficacy of SGLT-2 inhibitors (SGLT-2i) in kidney transplant recipients with pre-existing diabetes or post-transplant diabetes mellitus (PTDM). Topics include the benefits of SGLT-2i in preserving graft function, reducing glycemic burden, and potentially lowering cardiovascular risk in this patient group.

The article presents an evidence-based summary which determines the benefits and harms of metformin in the management of Type 2 diabetes compared to standard care or placebo. A 2012 meta-analysis of 13 studies by Boussageon and colleagues was used as a primary source of the evidence-based summary. Results revealed that no significant reduction in any efficacy outcome and no increase in severe hypoglycemic episodes.

Lipodystrophies involve the loss of subcutaneous adipose tissue, resulting in severe metabolic issues such as insulin resistance and challenging diabetes management. This case series aims to assess bromocriptine treatment response in lipodystrophy patients, offering insights into its antidiabetic effects. This retrospective analysis focused on four female lipodystrophy patients with poor glycemic control who were undergoing bromocriptine treatment. Statistical analysis used nonparametric tests. Metabolic parameters were assessed before and 3 months post-bromocriptine treatment, revealing a modest reduction in median daily insulin dose and decreased hemoglobin A1c and fasting glucose levels. Body weight remained constant, while triglyceride levels increased. Dopamine receptor expression in pancreatic ß-cells and adipocytes suggests a direct impact on glucose homeostasis. While this case series hints at bromocriptine's positive influence on glycemic control and insulin requirements in lipodystrophy patients, larger studies are essential for establishing efficacy and safety. [ABSTRACT FROM AUTHOR]

This editorial comments on the article by Haider et al. [ABSTRACT FROM AUTHOR]

Abstract Type-2 diabetes (T2D) worsens stroke recovery, amplifying post-stroke disabilities. Currently, there are no therapies targeting this important clinical problem. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are potent anti-diabetic drugs that also efficiently reduce cardiovascular death and heart failure. In addition, SGLT2i facilitate several processes implicated in stroke recovery. However, the potential efficacy of SGLT2i to improve stroke recovery in T2D has not been investigated. Therefore, we determined whether a post-stroke intervention with the SGLT2i Empagliflozin could improve stroke recovery in T2D mice. T2D was induced in C57BL6J mice by 8 months of high-fat diet feeding. Hereafter, animals were subjected to transient middle cerebral artery occlusion and treated with vehicle or the SGLTi Empagliflozin (10 mg/kg/day) starting from 3 days after stroke. A similar study in non diabetic mice was also conducted. Stroke recovery was assessed using the forepaw grip strength test. To identify potential mechanisms involved in the Empagliflozin-mediated effects, several metabolic parameters were assessed. Additionally, neuronal survival, neuroinflammation, neurogenesis and cerebral vascularization were analyzed using immunohistochemistry/quantitative microscopy. Empagliflozin significantly improved stroke recovery in T2D but not in non-diabetic mice. Improvement of functional recovery was associated with lowered glycemia, increased serum levels of fibroblast growth factor-21 (FGF-21), and the normalization of T2D-induced aberration of parenchymal pericyte density. The global T2D-epidemic and the fact that T2D is a major risk factor for stroke are drastically increasing the number of people in need of efficacious therapies to improve stroke recovery. Our data provide a strong incentive for the potential use of SGLT2i for the treatment of post-stroke sequelae in T2D.

Overloaded glucose levels in several metabolic diseases such as type 2 diabetes (T2D) can lead to mitochondrial dysfunction and enhanced production of reactive oxygen species (ROS). Oxidative stress and altered mitochondrial homeostasis, particularly in the cardiovascular system, contribute to the development of chronic comorbidities of diabetes. Diabetes-associated hyperglycemia and dyslipidemia can directly damage vascular vessels and lead to coronary artery disease or stroke, and indirectly damage other organs and lead to kidney dysfunction, known as diabetic nephropathy. The new diabetes treatments include Na+-glucose cotransporter 2 inhibitors (iSGLT2) and glucagon-like 1 peptide receptor agonists (GLP-1RA), among others. The iSGLT2 are oral anti-diabetic drugs, whereas GLP-1RA are preferably administered through subcutaneous injection, even though GLP-1RA oral formulations have recently become available. Both therapies are known to improve both carbohydrate and lipid metabolism, as well as to improve cardiovascular and cardiorenal outcomes in diabetic patients. In this review, we present an overview of current knowledge on the relationship between oxidative stress, mitochondrial dysfunction, and cardiovascular therapeutic benefits of iSGLT2 and GLP-1RA. We explore the benefits, limits and common features of the treatments and remark how both are an interesting target in the prevention of obesity, T2D and cardiovascular diseases, and emphasize the lack of a complete understanding of the underlying mechanism of action. [Display omitted] • T2D induces mitochondrial dysfunction and oxidative stress, fostering chronic comorbidities. • iSGLT2 and GLP-1RA enhance glycemic, carbohydrate, and lipid control in T2D. • iSGLT2 and GLP-1RA prevent cardiovascular, kidney diseases, and death. • iSGLT2 and GLP-1RA ease mitochondrial function, oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Study Objective: Studies have demonstrated sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are kidney protective; however, their ability to cause hemodynamic changes may predispose patients to acute kidney injury (AKI). An FDA warning recommends evaluating for factors that predispose patients to AKI before initiating a SGLT2 inhibitor. The primary objective of this study is to identify risk factors that may predispose persons with diabetes to AKI when initiating SGLT2 inhibitor therapy. Design: Multicenter retrospective cohort chart review. Data Source: Study patients were identified through an electronic medical record generated report if they had type 2 diabetes and were prescribed a SGLT2 inhibitor from January 2013 to September 2019. Patients: Patients were included if they were receiving care at Advocate Medical Group and were confirmed to have taken one of the four SGLT2 inhibitors available at the time of study approval, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, for at least 7 days. Patients were excluded if they did not have a basic metabolic panel or comprehensive metabolic panel recorded 1 year prior to or 6 months after SGLT2 inhibitor therapy initiation. Results: Data extraction from the electronic medical record identified 6425 patients receiving a SGLT2 inhibitor, of which 1962 met inclusion criteria and were included for analysis. Thirty‐five (1.8%) patients experienced an AKI after SGLT2 inhibitor therapy initiation. There was no statistically significant difference between groups based on background medication use (p = 0.325). At baseline, patients experiencing an AKI after SGLT2 inhibitor initiation were more likely to be older in age (p = 0.010), have a higher serum potassium (p < 0.001), blood glucose (p = 0.018), SCr (p = 0.009) and UACR (p < 0.001), and a lower eGFR (p = 0.028) compared to those who did not experience AKI. Conclusions: The transient eGFR decline with SGLT2 inhibitor initiation should be expected and is generally not an indication to discontinue therapy. Future initiatives should be directed at increasing knowledge of monitoring recommendations for these agents. [ABSTRACT FROM AUTHOR]

A study conducted in Korea found that sodium-glucose cotransporter 2 inhibitors (SGLT2is) were prescribed to 25.7% of diabetic patients hospitalized for cardiovascular diseases (CVDs), while glucagon-like peptide 1 receptor agonists (GLP-1RAs) were prescribed to only 1.8% of patients. Clinical trials have shown that both SGLT2is and GLP-1RAs significantly reduce cardiovascular events in patients with type 2 diabetes and established CVDs. SGLT2is have a greater effect on reducing heart failure hospitalizations, while GLP-1RAs have a greater effect on reducing major adverse cardiovascular events. The article emphasizes the need for guidelines to prioritize SGLT2is in heart failure and to refine the indications for GLP-1RAs. [Extracted from the article]