Classes Of Antidiabetic Medications Research Articles

The role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in epicardial adipose tissue modulation: a meta-analysis

Abstract Introduction Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications, renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk. Purpose This meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on epicardial adipose tissue. Methods We performed a literature search for studies assessing epicardial adipose tissue before and after treatment with a SGLT2 inhibitor compared to a control group. We excluded reviews, editorials, case reports/case series, and studies that did not use SGLT2 inhibitors or did not have a control group for comparison. The main outcome of interest was the change in EAT volume/thickness at follow-up. Effect sizes are presented as standardized mean difference (SMD) with their corresponding 95% confidence intervals (CIs) and were pooled based on a random-effects model. The leave-one-out sensitivity analysis was used for further validation of the findings. Publication bias was assessed by funnel plot inspection and egger’s regression test. Results The literature search yielded 49 results. After application of the exclusion criteria, a total of 6 studies were selected for data extraction and inclusion in the meta-analysis. Accordingly, we detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial between-study heterogeneity (I2: 94%, p<0.01). Results remained robust even after exclusion of any single study. Funnel plot inspection and egger’s regression test did not indicate the presence of publication bias. Conclusion This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure outcomes.Figure

Trends in anti-diabetic medication use, severe hyperglycaemia and severe hypoglycaemia among American Indian and Alaska Native Peoples, 2009-2013.

Type 2 diabetes (T2D) and its complications disproportionally affect American Indian and Alaska Native (AI/AN) peoples. Prescribing decisions for anti-diabetic medications are complicated and require balancing medication benefits, costs and side effects. Little is known about trends in anti-diabetic medication use as well as acute diabetes complications among AI/AN adults. Here, we examined patterns and trends in anti-diabetic medication use and rates of hospital admissions or emergency department (ED) visits due to severe hypoglycaemia and hyperglycaemia among AI/AN adults with T2D. We conducted a retrospective analysis of Indian Health Service (IHS) Improving Health Care Delivery Data Project. A total of 39 183 AI/AN adults aged ≥18 years with T2D who used IHS or Tribal health services during any of the fiscal years (FYs) 2009-2013 were included. Utilization rates of each class of anti-diabetic medications and rates of severe hypoglycaemia and severe hyperglycaemia in emergency room and/or inpatient discharge diagnoses were calculated for each year. Longitudinal statistical models were fitted to examine time trends of anti-diabetic medication use and complications. During 2009-2013, use of metformin (56.0%-60.5%), insulin (31.4%-35.9%) and dipeptidyl peptidase-4 inhibitors (1.4%-9.0%) increased, whereas the use of sulfonylureas (40.3%-32.9%) and thiazolidinediones (TZDs, 31.6%-8.8%) decreased significantly. Trends in severe hypoglycaemia (1.6%-0.8%) and severe hyperglycaemia (2.0%-1.6%) declined gradually. There were significant changes in the utilization of different anti-diabetic medication classes during 2009-2013 among AI/AN adults with T2D. Concurrently, there were significant reductions in severe hypoglycaemia and severe hyperglycaemia.

6680 GLP-1 Agonists in Type 1 Diabetes - Indications and Use

Abstract Disclosure: P. Panjawatanan: None. N. Radovanovic: None. R.J. Comi: None. Introduction: Insulin therapy is the mainstream treatment in patients with Type 1 diabetes. The use of insulin, though mimicking normal physiology, is associated with weight gain. Glucagon-like peptide 1 (GLP-1) agonists are a class of antidiabetic medication that lowers blood sugar levels and helps promote weight loss. We propose that GLP-1 agonists can reverse the trend of weight gain and help lower hemoglobin A1C (A1C) levels in patients with Type 1 diabetes who were gaining weight. Method: A retrospective chart review was performed at a single institution’s endocrine practice over five years. Patients with Type 1 diabetes with concomitant GLP-1 agonists used for at least one year were included. Observed outcomes were the change in A1C, weight, and basal insulin use compared at baseline, 6 months, and 12 months using mixed models repeated measures. The result was reported as estimated means (95%CI). Statistical significance was determined by a p-value less than 0.05. Results: There were 49 patients included in the study. The mean age was 44.7 years old. There were 32 females (65.3%) and 17 males (34.7%). The mean duration of diabetes was 24.6 years. Thirty-five patients (71.4%) used insulin pumps, and fourteen (28.6%) were on multiple daily injections. Overall, patients had been gaining an average of 2.0 kg per year. After the treatment with GLP-1 agonists, weight was significantly reduced at 12 months (90.0 kg (95%CI 84.9-95.1), p<0.001) compared to baseline (97.6 kg (95%CI 92.7-102.5)). The A1C was significantly improved at 12 months (7.6% (95%CI 7.2-7.9), p<0.001) compared to the baseline (8.2% (95%CI 7.9-8.6)). Total daily basal dose was significantly reduced at 12 months (35.8 units (95%CI 29.8-41.9), p<0.001) compared to the baseline (39.2 units (95%CI 33.3-45.1)). The improvement in the parameters was more pronounced at 6 months after treatment but persisted at 12 months. Conclusion: Weight gain is a consequence of insulin usage in both Type 1 and Type 2 diabetes, which considerably impacts treatment outcomes and the development of comorbidities. We conclude that GLP-1 agonists are helpful to reverse the trend of weight gain and help lower A1C levels in patients with Type 1 diabetes who require life-long insulin treatment. Presentation: 6/3/2024

Effectiveness and Side Effect Incidence in a Real-World Digital Weight-Loss Service Using Compounded Semaglutide: A Retrospective Comparative Study

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were originally developed in the late 1980s as a class of antidiabetic medication. However, research over the past decade has found them to be a safe and effective weight-loss agent, which has led to the approval of GLP-1 RAs such as Semaglutide as a supplement to lifestyle obesity interventions in multiple countries. When Semaglutide has become commercially unavailable, digital weight-loss services (DWLSs) have prescribed a compounded form of the medication—a practice in which health professionals formulate a replica of the commercial medication to serve ongoing patient needs. Although compounding has been relatively common over the past century, prominent medical bodies have argued that compounding a relatively novel medication such as Semaglutide represents a major safety risk. This study retrospectively compared the weight and side effect outcomes of patients from a large Australian DWLS whose lifestyle coaching was supplemented with either compounded or pure Semaglutide (both groups following the same titration schedule). All data were extracted from the service’s central data repository. To be included in the weight loss analysis, patients needed to have received a minimum of four monthly medication orders between June 2023 and May 2024 and have submitted weight data between 90 and 150 days after the arrival of their first order. All patients who received at least one medication order within the same period were included in the side effect analysis. The mean four-month weight loss percentage was statistically lower in the compounded Semaglutide group (N = 923, M = 9.11, SD = ±5.76) compared to those in the pure Semaglutide group (n = 1858, M = 9.87, SD = ±6.46), t (2032) = −3.15, p = 0.0017. A statistically lower proportion of patients in the compounded Semaglutide group (71.61%) reported at least one side effect than patients in the pure Semaglutide group (77.40%) during the study period, X2 (1, N = 7683) = 32.32, p < 0.001. When side effects were disaggregated into severity categories, a statistical difference was only observed in mild side effects, X2 (1, N = 7683) = 59.16, p < 0.001. A significantly higher rate of patients from the pure Semaglutide group achieved the ten (50.54% vs. 44.64%), X2 (1, N = 7683) = 10.34, p < 0.001, and fifteen (21.42% vs. 12.78%), X2 (1, N = 7683) = 30.43, p < 0.001, percent weight loss thresholds than patients from the compounded Semaglutide group. The findings indicate that compounded Semaglutide can be used as a component of tightly controlled DWLSs with slightly less effectiveness and but with slightly lower side effect incidence when compared to pure Semaglutide.

Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus

BackgroundThe Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) are a class of anti-diabetic medications that confer cardio-renal-metabolic (CRM) benefits. Emerging evidence also suggests that these agents provide better benefits for chronic pulmonary conditions, especially chronic obstructive pulmonary disease (COPD). Research questionWe aimed to assess the association between SGLT2i use and outcomes in patients with COPD and concomitant Type 2 Diabetes Mellitus (T2DM). Study design and methodsWe conducted a retrospective cohort study on adults with T2DM and COPD in a primary care clinic from January 01, 2019 to 01/01//2023. Patients were categorized into two groups based on SGLT2i use. We collected demographic information and outcomes such as emergency room (ER) visits, hospitalizations secondary to COPD exacerbation over the period of four years and time to hospitalization and ER visits. Chi-square analysis was used for categorical variables, whereas an unpaired t-test was used for continuous variables. Cox regression was performed to identify significant prognostic factors of hospitalization and ER visits. A Kaplan-Meir analysis was used to visualize the probability of non-hospitalization and the probability of not visiting the ER. Statistical significance was set at p-value <0.05. ResultsOf the 220 patients screened, 94 met the inclusion criteria, of which 20 patients (21.3 %) had SGLT2i use at admission, and 74 (78.7 %) did not. Baseline demographic information were well-matched between the two groups. SGLT2i use was associated with a significant reduction in ER visits (70 % vs. 97.3 %, p-0.001) and the number of hospitalizations (55 % vs 87.8 %, p-0.001). Further multivariate analysis showed lower hazards of hospitalization (adjusted HR-0.156; CI:0.073 to 0.331) and ER visits (HR)-0.232; CI:0.118 to 0.453) in patients on SGLT2i. InterpretationIn patients with T2DM with COPD, SGLT2i use was associated with reduced ER visits and hospitalizations related to COPD. This protective effect of SGLT2i could be explained by reduced systemic proinflammatory markers and increased anti-inflammatory markers via inhibition of Node like receptor protein 3(NLRP3) inflammasome activation in multiple tissues, including the lungs.

Empagliflozin: Primus Inter Pares Among Sodium-Glucose Cotransporter-2 Inhibitors?

Sodium/glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antidiabetic medications which have proved capable of providing breakthrough cardiovascular (CV) benefits in a variety of clinical scenarios, including patients with heart failure or obesity, irrespective of diabetic status. Several SGLT2 inhibitors are available, but the most prominent ones are canagliflozin, dapagliflozin, and empagliflozin. Several studies have focused on empagliflozin and its effects on the risk of heart failure incidence and recurrences. Most recently, empagliflozin has been recently tested in patients with recent myocardial infarction in the EMPAgliflozin on Hospitalization for Heart Failure and Mortality in Patients With aCuTe Myocardial Infarction randomized trial, with apparently ambiguous findings. The present viewpoint succinctly illustrates the main features of SGLT2 inhibitors as a pharmacologic class, their ever expanding role as a CV medication, and the comparative effectiveness of different individual SGLT2 inhibitors, explicitly commenting on the recent data on empagliflozin in patients with acute myocardial infarction. The reader will find in this article a poignant perspective on this novel avenue for CV prevention and treatment, which greatly expands the management armamentarium of CV practitioners. Indeed, we make the case that SGLT2 inhibitors have a clearly favorable class effect, with differences between individual agents mainly suitable for personalization of care and minimization of side effects.

Curcumin, a bioactive compound of Turmeric (Curcuma longa) and its derivatives as α-amylase and α-glucosidase inhibitors.

Diabetes mellitus (DM) is a long-term metabolic disease characterised by a controlled metabolism of fat, carbohydrates, and proteins. In recent decades, it has grown into a significant global public health issue. According to the International Diabetes Federation, there were 425 million DM globally in 2017, and the number might be increased to 629 million by 2045 (a global 48% increase). Approximately 4.2 million deaths globally attributed to DM occur before the age of 60. The existing class of anti-diabetic medications is limited by side effects, which has led to the hunt for novel inhibitors that specifically target the α-amylase and α-glucosidase enzymes. Curcumin is a small-molecular-weight compound found in the roots of the Curcuma longa L (C. longa). plant, which has been used for culinary, medicinal, and other purposes throughout Asia for thousands of years. Curcumin has potent anti-inflammatory, anti-cancer, anti-angiogenic, antispasmodic, antibacterial, and anti-parasitic qualities. Even though the potential of curcumin to cure DM has been well investigated, its low solubility, rapid metabolism, and short plasma half-life have limited its application in DM. Therefore, the objectives of this review were to review the chemical composition of C. longa, the structure of curcumin, the degradation of curcumin, and the effects of curcumin derivatives on anti-diabetic properties against α-amylase and α-glucosidase enzymes. The results showed that C. longa contains carbohydrates, moisture, protein, fat, minerals, volatiles, fibre, and curcuminoids. Among the curcuminoids, curcumin is 60-70% present in C. longa. Moreover, curcumin and its derivatives have a lot of potential for treating DM, which was highlighted in this review. This review emphasises the several biological applications of curcumin, which collectively establish the foundation for its anti-diabetic characteristics. Considering these results, curcumin derivatives may be considered as potential agents in the pharmacotherapeutic management of patients with DM.

Discerning computational, in vitro and in vivo investigations of self-assembling empagliflozin polymeric micelles in type-2 diabetes.

Empagliflozin (EMPA) is an SGLT2 inhibitor, a new class of anti-diabetic medication, indicated for treating type-2 diabetes. Its low permeability, poor solubility and bioavailability limits its use in management of diabetes. The study was aimed to formulate EMPA loaded polymeric micelles (PMs) to overcome these obstacles in oral absorption. In silico studies-molecular docking, molecular dynamic simulation (MDS), and quantum chemical calculation were employed to study the interaction of EMPA with different polymers. EMPA loaded TPGS polymeric micelles (EMPA-TPGS-PMs) were formulated by direct dissolution method and characterized in terms of surface morphology, entrapment, particle size, in vitro drug release, and in vitro cytotoxicity (HEK293 cells). In vivo pharmacokinetic and pharmacodynamic studies were also performed. The results suggested a good interaction between TPGS and EMPA with lowest binding energy compared to other polymers. Further MDS results and DFT calculations validated the stable binding of the complex hence TPGS was selected for further wet lab experiments. The EMPA-TPGS complex displayed lower value of Total energy (T.E.) than its individual components, indicating the overall stability of the complex while, the energy band gap (∆E) value lied between the two individual molecules, signifying the better electron transfer between HOMO and LUMO of the complex. Based on the solubility, entrapment and cytotoxicity studies, 5% TPGS was selected for formulating drug loaded micelles. EMPA-TPGS5-PMs presented a size of 9.008 ± 1.25nm, Polydispersity index (PDI) of 0.254 ± 0.100, a controlled release behaviour upto 24h. SEM and AFM images of the nanoformulation suggested spherical particles whereas, DSC, and PXRD studies confirmed the loss of crystallinity of EMPA. A 3.12-folds higher AUC and a greater reduction in blood glucose levels was exhibited by EMPA-TPGS5-PMs in comparison to EMPA-SUSP in mice model. EMPA-TPGS-PMs has exhibited better bio absorption and therapeutic effectiveness in diabetes treatment. This improved performance would open the possibility of dose reduction, reduced dosing frequency & dose-related side effects, improving pharmaco-economics and thereby improved overall compliance to the patient. However, this translation from bench to bedside would necessitate studies in higher animals and human volunteers.

Systematic Review of Cardiovascular Outcomes with Sulfonylureas, GLP-1 RA, and DPP-4 Inhibitors in Type 2 Diabetes Mellitus

Abstract Type 2 diabetes mellitus (T2DM) significantly increases the risk of cardiovascular diseases. Despite advances in glycemic control, managing cardiovascular risk remains a critical challenge. This systematic review aims to assess and compare the cardiovascular outcomes associated with three classes of antidiabetic medications: sulfonylureas, Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM. A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases, including PubMed, Embase, Cochrane Library, and Google Scholar, were searched for relevant studies published between 2019 and 2023. Inclusion criteria were adults (≥18 years) with T2DM, studies assessing cardiovascular outcomes with the specified medications, randomized controlled trials, observational studies, or meta-analyses. Two independent reviewers performed data extraction and risk of bias assessments. From the initial 1,543 records, 12 studies were included involving 61,534 patients. As a result, GLP-1 RAs demonstrated favorable cardiovascular safety and efficacy, particularly in reducing major adverse cardiovascular events and all-cause mortality. DPP-4 inhibitors were associated with neutral cardiovascular outcomes but indicated an elevated risk of cardiac failure in some studies. In recent studies, sulfonylureas, previously associated with cardiovascular concerns, showed no consistent evidence of increased cardiovascular risk. These findings highlight the importance of personalized treatment strategies to optimize cardiovascular outcomes in patients with T2DM.

CO2 Association Between Classes of Antidiabetic Medications and Their Potential Risk or Protective Effects on Cancer: A Systematic Review and Network Meta-Analysis

CO2 Association Between Classes of Antidiabetic Medications and Their Potential Risk or Protective Effects on Cancer: A Systematic Review and Network Meta-Analysis

Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis.

Incretin-based drugs, a class of Antidiabetic medications (ADMs) used in the treatment of type 2 diabetes, may affect the incidence of prostate cancer (PCa). But real-world evidence for this possible effect is lacking. Therefore, the aim of this study is to assess the effect of incretin-based drugs on the incidence of PCa, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. We searched PubMed, Embase, and Cochrane Library databases for eligible studies through September 2023. Two independent reviewers performed screening and data extraction. We used the Cochrane Handbook for Systematic Reviews and the Newcastle-Ottawa Scale (NOS) to assess the quality of included randomized controlled trials (RCTs) and cohort studies. We did a meta-analysis of available trial data to calculate overall risk ratios (RRs) for PCa. A total of 1238 articles were identified in our search. After screening for eligibility, 7 high-quality studies met the criteria for meta-analysis, including 2 RCTs and 5 cohort studies, with a total of 1165,738 patients. Compared with the control group, we found that incretin-based drugs reduced the relative risk of PCa by 35% (95% confidence interval (CI), 0.17-0.49; P = .0006). In subgroup analysis, the RR values for GLP-1 receptor agonists and DPP-4 inhibitors were 62% (95% CI, 0.45-0.85; P = .003) and 72% (95% CI, 0.46-1.12; P = .14), respectively. Incretin-based drugs are associated with lower incidence of prostate cancer and may have a preventive effect on prostate cancer in patients with type 2 diabetes.

The IDEAL (Insulin therapy DE-intensificAtion with iglarLixi) Randomised Controlled Trial-Study Design and Protocol.

Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently asubstantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100U/ml and a GLP-1 RA lixisenatide. Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. ClinicalTrials.gov, identifier NCT04945070.

Long-term results of transferring the patient from therapy with glucagon-like peptide-1 receptor agonists in combination with metformin to a dipeptidyl peptidase-4 inhibitor in combination with pioglitazone and inhibitor of type 2 sodium-glucose cotransporter in type 2 diabetes

The pioglitazone belongs to the class of antidiabetic medications and has various pleiotropic effects. The evidence base for this medication, based on the results of randomized clinical trials, demonstrates convincing cardio- and cerebroprotective efficacy of pioglitazone, comparable to innovative glucose-lowering drugs from the classes of GLP-1 agonists and SGLT-2 inhibitors. Currently, in Russia, a fixed combination of pioglitazone and alogliptin is available. However, it should be noted that there has been a recent lack of GLP-1 agonists on the domestic pharmaceutical market, which raises questions about the choice of further tactics for patients who have been taking them until recently.This clinical case presents an example of the transformation of glucose-lowering therapy from a combined treatment regimen with semaglutide and metformin to the combined use of a fixed combination of alogliptin and pioglitazone with empagliflozin. Against the background of therapy change, a stable and pronounced glucose-lowering effect was obtained and confirmed after six months, comparable to GLP-1 receptor agonists without the effect of escape and hypoglycemia. No edema or weight gain was observed, and no other adverse events were detected, which allowed continuing the chosen glucose-lowering therapy. Strategic perspectives of the prescribed therapy were determined — reducing cardio- and cerebrovascular risk and improving the patient’s prognosis.

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, anti-diabetic drugs in heart failure and cognitive impairment: potential mechanisms of the protective effects.

Heart failure and cognitive impairment emerge as public health problems that need to be addressed due to the aging global population. The conditions that often coexist are strongly related to advancing age and multimorbidity. Epidemiological evidence indicates that cardiovascular disease and neurodegenerative processes shares similar aspects, in term of prevalence, age distribution, and mortality. Type 2 diabetes increasingly represents a risk factor associated not only to cardiometabolic pathologies but also to neurological conditions. The pathophysiological features of type 2 diabetes and its metabolic complications (hyperglycemia, hyperinsulinemia, and insulin resistance) play a crucial role in the development and progression of both heart failure and cognitive dysfunction. This connection has opened to a potential new strategy, in which new classes of anti-diabetic medications, such as glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, are able to reduce the overall risk of cardiovascular events and neuronal damage, showing additional protective effects beyond glycemic control. The pleiotropic effects of GLP-1R agonists and SGLT2 inhibitors have been extensively investigated. They exert direct and indirect cardioprotective and neuroprotective actions, by reducing inflammation, oxidative stress, ions overload, and restoring insulin signaling. Nonetheless, the specificity of pathways and their contribution has not been fully elucidated, and this underlines the urgency for more comprehensive research.

Treatment modification after initiating second-line medication for type 2 diabetes.

To describe changes in antidiabetic medication (ADM) use and characteristics associated with changes in ADM use after initiation of noninsulin second-line therapy. Retrospective cohort study. This study analyzed private health plan claims for adults with type 2 diabetes who initiated 1 of 5 index ADM classes: sulfonylureas, dipeptidyl peptidase 4 inhibitors (DPP4is), sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or thiazolidinediones. Analyses evaluated 3 treatment modification outcomes-discontinuation, switching, and intensification-over 12-month follow-up. Of 82,624 included adults, nearly two-thirds (63.6%) experienced any treatment modification. Discontinuation was the most common modification (38.6%), especially among patients prescribed GLP-1 RAs (50.3%). Switching occurred in 5.2% of patients and intensification in 19.8%. In adjusted analysis, compared with patients prescribed sulfonylureas, discontinuation risk was 7% higher (HR, 1.07; 95% CI, 1.04-1.10) among patients prescribed DPP4is and 28% higher (HR, 1.28; 95% CI, 1.23-1.33) among patients prescribed GLP-1 RAs. Compared with sulfonylureas, all other index ADM classes had higher risks of switching and lower risks of intensification. Younger age group and female sex were both associated with higher risks of all modifications. Compared with index ADM prescription by a family medicine or internal medicine physician, index prescription by an endocrinologist was associated with both lower discontinuation risk and higher intensification risk. Most patients experienced a treatment modification within 1 year. Results highlight the need for new prescribing approaches and patient supports that can maximize medication adherence and reduce health system waste.

Lower Incidence of Leukemia in Sodium Glucose Cotransporter-2 Inhibitor-Treated Patients with Type 2 Diabetes Mellitus: Result from Large Real-World Cohorts

Objective: Leukemia is the among the top ten most common cancer in the United States of America, with incidence of 14.0 per 100,000 people. While the incidence of non-Hodgkin lymphoma has significantly decreased, the incidence of leukemia has been stable during 2014-2018 [1]. In the meantime, sodium-glucose cotransporter-2 inhibitors (SGLT-2i), a comparatively new class of anti-diabetic medication, has gained significant popularity among clinician due to its cardioprotective and renoprotective properties. Several observational studies and meta-analyses explored the relationship between SGLT-2i and solid tumor, including bladder cancer and breast cancer [2, 3]. Nevertheless, contemporary data for SGLT-2i and leukemia are limited. This large cohort study was aimed to investigate the association between SGLT-2i and the risk of leukemia. Methods: This was a retrospective cohort study including patients with T2DM from 92 hospitals across the United States between 2015 and 2023. Inclusion criteria were patients with T2DM aged 18 years or older who newly initiated treatment with SGLT-2i or DPP-4i. Patients with a history of type 1 diabetes or malignancies were excluded. Propensity score matching was applied to each group to account for confounding factors, including demographic characteristics, comorbidities, laboratory data, and medication history. The primary outcome of interest was the occurrence of incident leukemia, including lymphoid leukemia, myeloid leukemia and monocytic leukemia. Kaplan-Meier analysis and log-rank tests were used to compare the outcomes across the cohorts, while hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional hazard regression model. Results: A total of 718,276 SGLT-2i initiators were matched to 1,159,112 DPP4i initiators diagnosed with T2DM. Among these, 3,429 incidents of leukemia were identified, with 1,148 occurring in the SGLT2i groups and 2,281 in the DPP-4i group after matching.The baseline characteristics, including ethnicity, comorbidities and medication history, were well-balanced between the two cohorts. SGLT-2i initiators demonstrated a significantly reduced risk of new-onset leukemia compared to those using DPP-4i, including myeloid leukemia (HR, 0.676; 95% CI, 0.589 to 0.776, p &amp;lt; 0.001) and lymphoid leukemia (HR, 0.846; 95% CI, 0.753-0.950, p = 0.005). There was no significant difference in the occurrence of monocytic leukemia (aHR 0.836; 95% CI, 0.556 to 1.257, p = 0.388). Conclusion: This population-based propensity-score matched cohort study showed that SGLT-2i is associated with lower in the risk of developing leukemia when compared to those treated with DPP-4i. These findings highlight the potential therapeutic value of SGLT-2i in the prevention of hematological malignancies in patients with T2DM. Further clinical trials are necessary to explore and validate the potential applications. Reference 1. Cronin, K.A., et al., Annual report to the nation on the status of cancer, part 1: National cancer statistics. Cancer, 2022. 128(24): p. 4251-4284. 2. Garcia, M., et al., SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database. J Clin Pharmacol, 2021. 61(2): p. 187-192. 3. Tang, H., et al., SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Diabetologia, 2017. 60(10): p. 1862-1872.

Changes in Cardiovascular and Renal Biomarkers Associated with SGLT2 Inhibitors Treatment in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus is a major health problem worldwide with a steadily increasing prevalence reaching epidemic proportions. The major concern is the increased morbidity and mortality due to diabetic complications. Traditional but also nontraditional risk factors have been proposed to explain the pathogenesis of type 2 diabetes mellitus and its complications. Hyperglycemia has been considered an important risk factor, and the strict glycemic control can have a positive impact on microangiopathy but not macroangiopathy and its related morbidity and mortality. Thus, the therapeutic algorithm has shifted focus from a glucose-centered approach to a strategy that now emphasizes target-organ protection. Sodium-glucose transporter 2 inhibitors is an extremely important class of antidiabetic medications that, in addition to their glucose lowering effect, also exhibit cardio- and renoprotective effects. Various established and novel biomarkers have been described, reflecting kidney and cardiovascular function. In this review, we investigated the changes in established but also novel biomarkers of kidney, heart and vascular function associated with sodium-glucose transporter 2 inhibitors treatment in patients with type 2 diabetes mellitus.

Role of metformin in the management of type 2 diabetes: recent advances.

Metformin is one of the oldest antidiabetic medications, commonly used in the management of type 2 diabetes. Its mechanism of action is based on reducing glucose production in the liver, decreasing insulin resistance, and increasing insulin sensitivity. The drug has been studied extensively and has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia. It has been used for the treatment of obesity, gestational diabetes, and polycystic ovary syndrome. According to current guidelines, metformin can be used as the first‑line agent in the management of diabetes; however, in individuals with type 2 diabetes who would benefit from cardio‑renal protection, newer agents, such as sodium‑glucose cotransporter‑2 inhibitors and glucagon‑like peptide‑1 receptor agonists, are favored as the first‑line therapy. The novel classes of antidiabetic medications have demonstrated significant positive effects on glycemia with added benefits in patients with obesity, renal disease, heart failure, and cardiovascular disease. The emergence of these more effective agents has significantly altered the way diabetes is managed, thus prompting re‑evaluation of metformin as the initial therapy for all patients with diabetes.

Renal protection and safety of sodium-glucose cotransporter-2 inhibitors in chronic kidney disease.

Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, is shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety. Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3. Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group. SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Effectiveness of the Lilly Connected Care Program in Improving Glycemic Management Among Patients With Type 2 Diabetes in China: Retrospective Real-world Study.

Type 2 diabetes mellitus (T2DM) is a worldwide public health concern. Mobile health management platforms could be a potential way to achieve effective glycemic control. This study aimed to evaluate the real-world effectiveness of the Lilly Connected Care Program (LCCP) platform in glycemic control among patients with T2DM in China. This retrospective study included Chinese patients with T2DM (aged ≥18 years) from April 1, 2017, to January 31, 2020, for the LCCP group and from January 1, 2015, to January 31, 2020, for the non-LCCP group. Propensity score matching was used to match the LCCP and non-LCCP groups to reduce confounding, with covariates including age, sex, the duration of diabetes, baseline hemoglobin A1c (HbA1c), and the number of oral antidiabetic medication classes. HbA1c reduction over 4 months, the proportions of patients achieving an HbA1c reduction of ≥0.5% or ≥1%, and the proportions of patients reaching to target HbA1c level of ≤6.5% or <7% were compared between the LCCP and non-LCCP groups. Multivariate linear regression was used to assess factors associated with HbA1c reduction. A total of 923 patients were included, among whom 303 pairs of patients were well matched after propensity score matching. HbA1c reduction during the 4-month follow-up was significantly larger in the LCCP group than the non-LCCP group (mean 2.21%, SD 2.37% vs mean 1.65%, SD 2.29%; P=.003). The LCCP group had a higher proportion of patients with an HbA1c reduction of ≥1% (209/303, 69% vs 174/303, 57.4%; P=.003) and ≥0.5% (229/303, 75.6% vs 206/303, 68%; P=.04). The proportions of patients reaching the target HbA1c level of ≤6.5% were significantly different between the LCCP and non-LCCP groups (88/303, 29% vs 61/303, 20.1%; P=.01), whereas the difference in the proportions of patients reaching the target HbA1c level of <7% was not statistically significant (LCCP vs non-LCCP: 128/303, 42.2% vs 109/303, 36%; P=.11). LCCP participation and higher baseline HbA1c were associated with a larger HbA1c reduction, whereas older age, longer diabetes duration, and higher baseline dose of premixed insulin analogue were associated with a smaller HbA1c reduction. The LCCP mobile platform was effective in glycemic control among patients with T2DM in China in the real world.