Oral Antidiabetic Medications Research Articles

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control.

The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.

TRELAGLIPTIN'S REAL WORLD EFFICACY AMONG TYPE 2 DIABETES PATIENTS IN CAMBODIA (TRELA -REAL STUDY)

Background: Trelagliptin is the rst once-weekly oral therapy for type 2 diabetes in Cambodia. The afrmation of its efcacy and safety in Cambodian Type 2 Diabetes patients is to be established for extending the clinical benet of this unique oral anti-diabetic agent in this population Objective: To conrm the effect of Trelagliptin (TRELA), a selective once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, on glycemic control in the management of Type 2 Diabetes Mellitus (T2DM) in real-world practice settings in Cambodia Methods: An open-label, multicentric prospective, observational single-arm study was conducted across Phnom Penh and three other provinces in Cambodia which will include Siem Reap, Kampong Cham, and Battambang in outpatient settings. One hundred and fty patients with Type 2 Diabetes were enrolled after seeking informed consent. Trelagliptin 100 mg one tablet per week was administered to patients with type 2 diabetes who showed poor glycemic control (HbA1c ≥6.5% ) on diet/exercise therapy alone or diet/exercise therapy plus other oral antidiabetic agents or insulin. The study primary endpoint(s) included changes in glycated hemoglobin (HbA1c) from baseline at the end of three months, and at the end of six months of the study. The secondary endpoints included patient satisfaction and investigator assessment at the end of treatment (6 months) to once weekly treatment to Trelagliptin. Result: Treatment with Trelagliptin 100 mg/week led to a mean change in HbA1c 0.86% (from 8.76 ± 2.02 to 7.9 ± 1.60, p < 0.05, CI 95) at the end of 3 months. At the end of 6 months, the mean change in HbA1c was 1.26% (from 8.76 ± 2.02 to 7.5 ± 1.34), p<0.05, CI 95) (p-value signicant) Patient satisfaction and preference with once-weekly trelagliptin treatment was reported in 97.04 % (n=131) patients. As per the investigator's assessment, 77.04 % (n=104) of the patients reported a “good” response to Trelagliptin treatment at the end of the study over a period of 6 months. In 14.07 % (n=19) patients investigators reported that “excellent” response was achieved. Whereas 5.19% (n=7) and 3.7% (n=5) patients reported average and poor responses, respectively. Trelagliptin treatment once a week was demonstrated to be clinically efcacious as monotherapy and in combination with other anti-hyperglycemic agents. Trelagliptin treatment was found to be efcacious in treatment naïve and treatment-experienced patients. The clinical benets of Trelagliptin were consistent across age groups, body mass index (BMIs), and associated co-morbidities like hypertension. Trelagliptin was well tolerated and was safely used in addition to Metformin, Sulfonylureas, Thiazolidinediones, SGLT2-inhibitors & Insulin treatment. The glucose-lowering effect of Trelagliptin was comparable to other DPP4 inhibitors (gliptins), and other classes of oral anti-diabetic medications with the additional advantage of once-a-week dosing treatment regime. Conclusion: Treatment with once-a-week trelagliptin as initial monotherapy and in combination therapy with other anti-hyperglycemic agents for glucose control in Type 2 Diabetes was efcacious and well-tolerated. Trelagliptin 100 mg once a week treatment achieved treatment satisfaction in most patients and reported “good” investigator response in majority of type 2 diabetes patients. Trelagliptin 100 mg once-a-week treatment is a useful consideration in the management of type 2 diabetes patients

A nutraceutical approach towards corn silk

Corn silk is an herb plant used as traditional medicine throughout the world to treat many diseases. The scientific name of corn silk is Stigma Maydis. Corn silk consists, of carbohydrates, vitamins, and proteins some calcium, Na salts, K, and Magnesium. Corn silk contains volatile oils, certain steroids such as stigmasterol and sitosterol, tannins, saponins, alkaloids, and flavonoids. Organic acids found in corn silk include formic acid, oleic acid, palmitic acid, linoleic acid, stearic acid, succinic acid, and lactic acid. For decades, corn silk has been used as a diuretic, Antilithiatic, and uricosuric, as well as to treat cystitis, gout, and kidney stone and as an oral antidiabetic medication. The antioxidant potential of the corn silk and its healthcare applications as agents of diuretics, for the reduction of hyperglycemia, as an anti-fatigue, and as an anti-depressant, use have been claimed in many studies. Teas and supplements of corn silk are used to treat urinary-related problems. The present reviews will provide the complete health potential of corn silk.

Use of insulin degludec/aspart after resolution of euglycemic diabetic ketoacidosis associated with dapagliflozin in a female patient with newly diagnosed maturity onset diabetes of the young type 3

Abstract Introduction Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by beta cell dysfunction. MODY presents generally at a young onset, and usually does not prone to ketosis. MODY should be distinguished from type 1(T1D) or type 2 diabetes(T2D), because the treatment modalities may be different. In this case, we aimed to emphasize the successful use of insulin degludec/aspart (IDegAsp) after resolution euglycemic diabetic ketoacidosis (euDKA) in a patient latterly diagnosed with MODY. Clinical Case A 39-year-old female patient was referred to our clinic with severe hyperglycemia. SMBG results revealed that blood glucose levels were about 300–400 mg/dL indicating severe hyperglycemia. She has been followed up for T2D 15 years and had been taking oral antidiabetic regimen until 6 months ago. Insulin glargine was prescribed 6 months ago, but she gave up insulin and had been taking linagliptin 5 mg/day and dapagliflozin 10 mg/day. The previous history was remarkable for arrhythmia which was treated with ablation 15 years ago. Maternal history of T2D was present. On physical examination, heart rate was 100/min, and systemic examination findings were in normal range except for central obesity. Laboratory evaluation revealed that fasting blood glucose was 212 mg/dL, HbA1c 10.2%, creatinine 1.1 mg/dL, and ketone 3+ in urinalysis. Arterial blood gas analysis revealed mild acidosis (pH 7.25, HCO3 18 mmol/L). The patient was hospitalized with a diagnosis of euDKA. Intravenous hydration with 0.9% NaCL and regular insulin was administered, and oral antidiabetic medications were stopped. In the follow-up, intensive insulin regimen (preprandial insulin glulisine 3×5 unit and basal insulin glargine 1×15 unit) was given after the resolution of euDKA. Although dose adjustments, two attacks of near-hypoglycemia (71 and 77 mg/dL) were detected in the first week after resolution of euDKA. IDegAsp (premeal 2×12 unit) was substituted for glargine and glulisine. Due to the maintenance of glycemic regulation by oral antidiabetic regimen for a long period, and the existence of maternal history of T2D, genetic analysis was performed with a pre-diagnosis of MODY. To exclude T1D, we demonstrated that autoantibodies (islet cell antibody 5.01 U/mL, and Anti-GAD antibody 7.74 IU/mL) for T1D were negative. HNF1A heterozygous mutation was detected, and MODY type 3 was diagnosed. HbA1c level was gradually regressed to 8.8%, and then to 6.3%. By the diagnosis of MODY type 3, gliclazide treatment was considered. Basal fasting C-peptide level was measured as 1.22 ng/mL. The antidiabetic regimen was revised as linagliptin 5 mg/day and gliclazide 30 mg/day, and insulin was stopped. Conclusion Some types of MODY is associated with mild hyperglycemia, however some others necessitate insulin treatment. The number of reports regarding the use of IDegAsp in MODY is limited. We reached HbA1c target with IDegAsp in a patient with MODY type 3 after resolution of euDKA.

Cytotoxic and genotoxic effects of nateglinide on human ovarian, prostate, and colon cancer cell lines

Objective: Nateglinide, an oral anti-diabetic medication used to treat type 2 diabetes, activates ATP-dependent potassium channels in pancreatic beta cells and induces insulin secretion. Numerous antidiabetic medicines, particularly metformin, are known to drastically reduce the viability of cancer cells. This study examined the effects of nateglinide on the DNA and viability of human ovarian (A2780), prostate (LNCaP), and colon (Caco-2) cancer cells. Materials and methods: Initially in the study, 1, 10, 100, and 1000 µM doses of nateglinide were administered for 24 hours to A2780, LNCaP, and Caco-2 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to measure cell viability. Using Graphpad Prism 8, the inhibitory logarithmic concentration values (LogIC50) of nateglinide in A2780, LNCaP, and Caco-2 cells were computed based on the results of the MTT experiment. These doses were applied to A2780, LNCaP, and Caco-2 cells for the Comet assay. The Bonferroni-corrected Mann–Whitney U test was used to compare groups, and a value of p<0.05 was considered statistically significant. Results: In A2780 and LNCaP cell lines, only 1000 μM nateglinide concentration decreased cell viability (p<0.05), whereas in Caco-2 cells, all concentrations except 1 μM reduced cell viability (p<0.05). The Comet assay indicated that nateglinide produced DNA damage by increasing the tail lengths and tail moments of A2780, LNCaP, and Caco-2 cells (p<0.05) and reducing the head diameters (p<0.05). Conclusion: According to the findings of this study, nateglinide has cytotoxic effects on human ovarian, prostate and colon cancer cell lines and may possess anticancer properties.

Data-Driven Identification of Long-Term Glycemia Clusters and Their Individualized Predictors in Finnish Patients with Type 2 Diabetes.

To gain an understanding of the heterogeneous group of type 2 diabetes (T2D) patients, we aimed to identify patients with the homogenous long-term HbA1c trajectories and to predict the trajectory membership for each patient using explainable machine learning methods and different clinical-, treatment-, and socio-economic-related predictors. Electronic health records data covering primary and specialized healthcare on 9631 patients having T2D diagnosis were extracted from the North Karelia region, Finland. Six-year HbA1c trajectories were examined with growth mixture models. Linear discriminant analysis and neural networks were applied to predict the trajectory membership individually. Three HbA1c trajectories were distinguished over six years: "stable, adequate" (86.5%), "improving, but inadequate" (7.3%), and "fluctuating, inadequate" (6.2%) glycemic control. Prior glucose levels, duration of T2D, use of insulin only, use of insulin together with some oral antidiabetic medications, and use of only metformin were the most important predictors for the long-term treatment balance. The prediction model had a balanced accuracy of 85% and a receiving operating characteristic area under the curve of 91%, indicating high performance. Moreover, the results based on SHAP (Shapley additive explanations) values show that it is possible to explain the outcomes of machine learning methods at the population and individual levels. Heterogeneity in long-term glycemic control can be predicted with confidence by utilizing information from previous HbA1c levels, fasting plasma glucose, duration of T2D, and use of antidiabetic medications. In future, the expected development of HbA1c could be predicted based on the patient's unique risk factors offering a practical tool for clinicians to support treatment planning.

Antidiabetic Therapy in Patients Related to CKD (Chronic Kidney Disease)

Patients with type 2 diabetes mellitus (T2DM) are more likely to have chronic kidney disease (CKD) in stages 3-5 (glomerular filtration rate [GFR] 60 mL/min) by roughly 25–30%. Despite the limits of most oral anti-diabetic medications in people with CKD, incretin-based treatments are being utilized more frequently to treat type 2 diabetes. This study examines the impact of CKD on the pharmacokinetics of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, as well as the efficacy/safety profile of these medications when used in patients with T2DM and CKD. Sitagliptin, Vildagliptin, Saxagliptin, and Alogliptin are the most common DPP-4 inhibitors that are primarily excreted by the kidneys. This led to recommendations for appropriate dose reductions based on the severity of CKD after pharmacokinetic studies revealed that total exposure to the medication is increased in proportion to the fall in GFR. Clinical investigations found that patients with CKD had a high effectiveness and safety profile under these circumstances. Lintagliptin, on the other hand, is primarily excreted through the hepatobiliary system. No dose adjustment of lintagliptin is necessary in the setting of CKD because a pharmacokinetic investigation revealed that lower GFR had a negligible impact on total exposure. Patients with CKD have less experience using GLP-1 receptor agonists. Exenatide should not be administered to patients with severe CKD because it is excreted through renal processes. Due to the limited experience with CKD patients, ligarglutide should be administered with caution even if the kidneys do not remove it from the body. For lixisenatide, exenatide long-acting release (LAR), and other once-weekly GLP-1 receptor agonists now under development, only scant pharmacokinetic data are also available. GLP-1 receptor agonists have been implicated in several case reports of acute renal failure, which was most likely brought on by dehydration brought on by gastrointestinal side effects. Nevertheless, improving GLP-1 may also have advantageous renal effects that could help lower the incidence of diabetic nephropathy. In conclusion, the physician has new chances due to the DPP-4 inhibitors' broad and encouraging experience in CKD patients, whereas the limited experience with GLP-1 receptor agonists in this population calls for greater caution.

Case Study Presenting Remarkable Improvements of all Parameters in a Long-Term T2DM Patient with Multiple Chronic Comorbidities by Sugar fit’s -Tech/Ai-Driven Platform with Daily Personalised Life Coaching and Expert Medical Advice

Background: Type 2 diabetes mellitus (T2DM) is not only one of the leading causes of mortality, but its impact on healthcare costs and burden is becoming unsustainable each year. The quality of life and life expectancy are both significantly impacted by this chronic metabolic condition. To help control their blood glucose levels, patients with T2DM adhere to a self-management regimen as instructed by a professional. Various technological options are available now to help self-management. Methods: Here, we present a case of a 64-year-old female with insulin-dependent type 2 diabetes mellitus, multiple co-morbidities, depression, confined to her room, and inability to walk for about a year. After six months of the Sugar fit approach with daily-personalized life coaching, expert medical advice, tech-enabled, AI-driven model, she showed tremendous improvement in every parameter. Results: Before joining sugar fit, the patient was on 44 units of rapid insulin and 18 units of long-acting and oral anti-diabetic medications. The patient’s Hba1c at baseline was 8%; six months later, it is 6.8% with all rapid and long insulin stopped and oral meds essentially the same as before. She has reduced creatinine from 1.88 to 1.37 and triglycerides from 1015 to 448, respectively. Her BP medications have been reduced to 50%. She walks for 2 km every day and is socially active with resolved depression. She has lost 3 kgs of weight and 3 inches of waist circumference. Conclusions: The findings indicate that a tech-enabled, AI-driven model with intensive, personalized coaching, lifestyle modification, and expert physician guidance has shown remarkable results even in this particularly complicated case. The findings indicate that the personalized and individualized frequent lifestyle coaching and expert physician opinion enabled by superior technology and AI-driven Insights resulted in marked improvement of all parameters and significant medication reductions even in Diabetes of long duration with comorbidities

Case report about treatment of the patient with DM Type 2 on multiple injections of insulin who with the help of continuous glucose monitoring (CGM) improved and was controlled only on anti-diabetic pills and GLP1 - RAG

We would like to describe a patient who was treated for decompensated Diabetes Mellitus Type 2(DM type 2) with Multiple Injections of Insulin per day. His HbA1c while when he visited our clinic was above 14 %. He was self-monitoring his Blood sugar at home (SMBG) 4- times a day. He was treated only with Metformin ER in the past. The CGM was started in Internal Medicine Residency Clinic. The patient start sharing his CGM data with the clinic through Dexcom G6 CGM and compatible I phone. The patient was educated on diet, how to adjust his insulin at home based on written instruction material. Moreover, the patient was called at least once a week by the Medicine Clinic professional how to adjust his insulin and to counsel him about his diet and physical activity. The patient had scheduled appointment to the clinic at least once a month. After the glucotoxicity from the initial high blood sugar was managed by using the appropriate dose of insulin, the insulin dosages started to decrease in our patient. DM type 2 was well controlled with GMI less than 7% after starting the CGM. During the clinic visits, the morning fasting C- peptide of the patient was increased which we attribute due to his morbid obesity. These gave us the opportunity to start the patients on per oral antidiabetic medications and injectable GLP-1 receptor agonists (GLP-1-RAG). The patient’s DM type 2 control was maintained 3-6 months after stopping the insulin with Glucose management index (GMI) which approximates HbA1c less than 7%. Our experience with this patient showed that introduction of CGM instead of SMBG in the General Internal Medicine Residency Clinic can help patients with DM type 2 to improve their blood sugar control with Insulin and eventually stop the Insulin and start therapy with oral antidiabetic agents and or injectable GLP-1 -RAG. Also, we showed that this can be done safely in General Internal Medicine Residency clinic and not only in specialized clinics.

Serum Level of Il-2 in Patients with Type 2 Diabetes Mellitus and Periodontopathy

The purpose of this study was to investigate the influence of low-level laser therapy (LLLT) in patients with type 2 diabetes mellitus (T2DM) and chronic periodontopathy (ChP) on serum levels of IL-2. Methods and Results: A total of 80 patients aged 35-60 years were followed; all of them had T2DM diagnosed (HbA1C≤7.5%) with ChP, where clinical attachment loss (CAL) was ≥4mm on at least 50% of affected teeth. All participants are divided into two groups. Group A included 40 patients who underwent conservative (non-surgical) periodontal treatment supplemented with LLLT. Group B included 40 patients who underwent only conservative therapy. Patients used oral antidiabetic medications to control glycemia: Metformin (Alkaloid, Skopje S. Macedonia) 500 mg two times a day. LLLT (Laser HF® comfort, Hager. Werken, Duisburg, Germany) was applied (660 nm, 10 mW, 8 min/day) with contact to the gingiva for five consecutive days. Serum IL-2 was determined by ELISA in 3 time intervals: at the first examination, 6 weeks, and 3 months after treatment in both groups. In Group A and Group B, at the first examination, 6 weeks after therapy, and 3 months after treatment, the serum IL-2 was 17.20±0.54 pg/ml and 17.22±0.66 pg/ml, 17.12±0.63 pg/ml and 17.17±0.63 pg/ml, and 17.03±0.64 pg/ml and 16.98±0.65 pg/ml, respectively. In Group A, there was a significant difference between the serum IL-2 values in specified time points (first examination, 6 weeks, and 3 months after the therapy) (Friedman’s ANOVA: χ² (n=40, df=2) = 17.22 and P=0.0002). In Group B, between the serum IL-2 levels, there also was a significant difference in specified time points (Friedman’s ANOVA: χ² (n=40, df=2) = 42.33 and P=0.0000). The intergroup analysis, according to the temporal dynamics of the measurements, showed an evident difference between the two groups, but the serum IL-2 values in the two groups treated with and without LLLT were close, and no statistical significance was recorded between them. Conclusion: No significant differences were recorded in the serum IL-2 levels in T2DM patients with ChP non-surgically treated with and without the application of LLLT.

A dynamic analysis of medication adherence.

BACKGROUND: Medication adherence is an important factor in maintaining and improving health, although adherence levels are often suboptimal. Previous studies have highlighted the importance of prior adherence behavior in understanding future adherence behaviors. OBJECTIVE: To improve understanding of adherence behavior and analyze the role of previous adherence in estimating the likelihood of future adherence for maintenance medications. METHODS: The adherence behaviors of 53,709 continuously enrolled individuals in employer-sponsored health plans were analyzed using a state-dependence framework (ie, adherence patterns in the past influence adherence in the future). This allowed for the estimation of the extent of carryover in adherence from one quarter to another while adjusting for observed and unobserved heterogeneity and enrollee characteristics. The role of the initial observation of adherence on the likelihood of future adherence was also analyzed. This study focuses on enrollee cohorts who filled prescriptions in 3 maintenance medication classes: lipid-lowering medications, antihypertensive medications, and oral antidiabetes medications. RESULTS: If an enrollee was adherent in the previous quarter, more than 80% of the time they remained adherent in the current quarter. Similarly, if they were nonadherent in the previous quarter, more than 75% of the time they remained nonadherent. Marginal effect estimates for prior adherence (previous quarter and initial quarter) showed increases in predicted adherence when adherent in the previous quarter (8.7 percentage points [pp] [95% CI = 8.0-9.3 pp] for lipid-lowering medications) and when adherent in the initial quarter (14.4 pp [13.8-15.1 pp] for lipid-lowering medications). Adherence in the initial and previous quarter increased predicted adherence considerably (22.7 pp [22.1-23.3 pp]). Similar patterns held for the antihypertensive medication cohort (antihypertensive medications) and the oral antidiabetes medication cohort (oral antidiabetes medications). The area under the curve (AUC) showed considerable improvement when moving from pooled probit models to dynamic random-effects probit models. AUC for the dynamic models exceeded 0.85 in the 3 medication cohorts, whereas the pooled probit models remained under 0.7. CONCLUSIONS: Adherence in the previous quarter is associated with adherence in the current quarter, after accounting for sources of observable and unobservable heterogeneity across enrollees. In addition, the initial value of adherence matters when explaining the likelihood of adherence.

EE459 Early Intensification of Oral Semaglutide in the UK: A Cost-Effectiveness Analysis Versus Continuing Metformin and SGLT-2 Inhibitor Therapy

A number of people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral antidiabetic medications such as metformin and sodium-glucose cotransporter-2 (SGLT-2) inhibitors rather than treatment-intensifying with a glucagon-like peptide-1 receptor agonist, despite an efficacious, orally administered option, oral semaglutide, being available. The present study evaluated the long-term cost-effectiveness of immediate oral semaglutide treatment versus continuing metformin plus SGLT-2 inhibitor therapy in the UK.

Effectiveness of an Interprofessional Program (Siscare) for Supporting Patients With Type 2 Diabetes.

To assess the effectiveness of an interprofessional support program (Siscare) that includes motivational interviews (patient-pharmacist), electronic monitoring (EM) of medications, patient-reported and clinical outcomes monitoring, and interactions with physicians for patients with type 2 diabetes in French-speaking Switzerland. This was a prospective, multicenter, observational cohort study using a hybrid implementation-effectiveness design. Individual daily adherence to at least one oral antidiabetic medication was measured by EM. A global adherence score was estimated by the product of a model-estimated implementation and a nonparametric estimate of persistence over time. Clinical outcomes (A1C, blood glucose, BMI, blood pressure, heart rate, and cholesterol levels) and quality of life (QoL) were analyzed over time using linear mixed-effect models. A total of 212 patients were included from 27 pharmacies; 120 patients (57%) were followed up for at least 15 months. In total, 140 patients (66%) were male, the mean age was 64 ± 11 years, and the mean number of chronic medications per patient at baseline was 5 ± 3. Of 178 patients who used EM, 95% (95% CI 92-99%) remained persistent at the end of the follow-up period. The percentage of persistent patients taking their medications appropriately (implementation) was stable during follow-up and was estimated to be 90% (95% CI 87-92%) at baseline and 88% (95% CI 84-91%) at month 15. At baseline, the mean A1C and BMI were 7.5% and 31 kg/m2, respectively, which decreased by 0.5% (P = 0.012) and 0.6 kg/m2 (P = 0.017), respectively, after 15 months. QoL remained stable during follow-up. The program supports medication adherence and improves clinical outcomes, illustrating the overall preventive effect of coordinated care.

Prevalence of Bacterial Urinary Tract Infection Among Patients With Type 2 Diabetes Mellitus on Sodium-Glucose Cotransporter-2 Inhibitors: A Prospective Real-World Setting Study.

Genitourinary tract infections, mycotic as well as bacterial, as defined by clinical symptoms, are one of the common adverse effects associated with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients in clinical trials. However, Indian data in terms of the prevalence of culture-proven bacterial type of urinary tract infection (UTI), and the causative organism is limited. This study aimed to determine the prevalence and causative agents of bacterial UTI among patients with T2DM on SGLT2i. This was a prospective longitudinal study involving all patients with T2DM who were prescribed with SGLT2i, uncontrolled on other oral anti-diabetic medications, from June 2019 to February 2020. Prevalence of bacterial UTI was evaluated at baseline and 12 weeks after initiation of SGLT2i. A total of 80 patients were started on SGLT2i. One female patient on canagliflozin had significant asymptomatic bacteriuria and the causative agent was Acinetobacter baumannii. One male patient on dapagliflozin had symptomatic UTI with negative urine culture study. Four patients developed genital mycotic infection. In this real-world study, SGLT2i as a class, was well tolerated with favorable safety profile, and risk of developing significant bacteriuria and/or symptomatic UTI was minimal.

Abstract #1314889: Oral Antidiabetic Medications Use in Patients with Uncontrolled T2DM who Refuse Insulin or Any Injectable Therapies

There is no guideline to provide a management roadmap for individuals with poorly controlled T2DM who refused insulin using different combinations of OADs. The objective is to evaluate 4 different combinations of OADs in individuals with uncontrolled T2DM who refused any injectable therapies.

New-Onset Diabetes Mellitus in Post-renal Transplant Patients on Tacrolimus and Mycophenolate: A Systematic Review.

A frequent complication in kidney transplantation is post-transplant diabetes mellitus (PTDM). The primary goal of this study is to review the risk factors and preventive methods and compare the different available anti-diabetic medications for the management of PTDM. We searched databases like Pubmed and Google Scholar for related articles using specific terms and phrases. Following a thorough investigation, we applied the inclusion and exclusion criteria and completed a quality assessment. Modifiable risk factors have a significant role in the development of PTDM.The combinations of immunosuppressive treatment tacrolimus (TAC), cyclosporine A (CYC), and everolimus (EVL), steroids increase the incidence of PTDM significantly. Insulin is the most effective treatment for PTDM in the early transplant period; however, oral anti-diabetic medications look promising. Further clinical trials are required to determine the optimum treatment method for reducing the occurrence of PTDM and treating the existing condition with novel anti-hyperglycemic medications.

Influences of Glimepiride Self-Nanoemulsifying Drug Delivery System Loaded Liquisolid Tablets on the Hypoglycemic Activity and Pancreatic Histopathological Changes in Streptozotocin-Induced Hyperglycemic Rats.

The development of an oral anti-diabetic medication characterized by enhanced hypoglycemic activity is in high demand. The goal was to study the hypoglycemic activity and pancreatic histopathology after the black-seed-based self-nanoemulsifying drug delivery system (SNEDDS) loaded with glimepiride liquisolid tablets to diabetic rats. The solubility of glimepiride in various vehicles was investigated. An optimization SNEDDS formulation was developed using a mixture of the experimental design approach. Box-Behnken design (BBD) was used to develop glimepiride liquisolid tablets utilizing Avicel PH 101 and Neusilin as a carrier mixture and FujiSil as a coating material. The quality attributes of the prepared tablets were assessed. Following the administration of the optimized tablets to diabetic rats, the pharmacodynamics and histopathological changes were investigated and compared to a commercial drug product. Results revealed that the optimized SNEDDS formulation that contains 15.43% w/w black seed oil, 40% w/w Tween 80, and 44.57% w/w Polyethylene glycol 400 showed an average droplet size of 34.64 ± 2.01 nm and a drug load of 36.67 ± 3.13 mg/mL. The optimized tablet formulation contained 0.31% Avicel in the carrier mixture, a 14.99 excipient ratio, and 8% superdisintegrant. Pre- and post-compression properties were satisfactory, and the optimized glimepiride liquisolid tablet showed a two-fold increase in dissolution. The optimized tablet demonstrated superior pharmacodynamics. The pancreatic tissues of the group treated with the optimized tablet displayed normal histological structure. The obtained data offered a commercially viable alternative for manufacturing solid dosage forms containing water-insoluble drugs, but additional clinical research is required.

Study Selection Bias and Racial or Ethnic Disparities in Estimated Age at Onset of Cardiometabolic Disease Among Midlife Women in the US

Racial disparities in cardiometabolic health are consistently observed in cohort studies. However, most studies neither evaluate differences in age at onset nor account for systematic exclusion stemming from "weathering" (accelerated health declines for minoritized groups due to structural social and economic marginalization). To evaluate racial or ethnic disparities in age at onset of 4 cardiometabolic outcomes (hypertension, isolated systolic hypertension [ISH], insulin resistance [IR], and diabetes), accounting for multiple forms of potential selection bias. This cohort study used data from the Study of Women's Health Across the Nation longitudinal cohort (1995-2016) and a cross-sectional screening sample (1995-1997). Data were analyzed from July 2019 to October 2021. Participants were eligible for the cohort if they were aged 42 to 52 years, had not received hormone therapy in the past 3 months, were not pregnant, had an intact uterus and at least 1 ovary, and were premenopausal or early perimenopausal (most recent menses ≤3 months). Self-reported racial or ethnic group (Black, Chinese, Hispanic, Japanese, or White). The main outcomes were hypertension (systolic blood pressure [BP] ≥140 mm Hg and diastolic BP ≥90 mm Hg or use of antihypertensive medication), ISH (systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg or use of antihypertensive medication), IR (homeostasis model assessment for IR value >5.9 or insulin use), and diabetes (fasting serum glucose level ≥126 mg/dL [to convert to mmol/L, multiply by 0.0555], use of insulin or oral antidiabetic medication, or physician diagnosis). Selection into the cohort was addressed via inverse probability weighting and interval-censored survival models and selection out via multiple imputation. Accelerated failure time models were used to examine racial or ethnic differences in age at disease onset and estimate the median age at onset. A total of 3302 women were included in the study, with a median age of 46.2 years (range, 42-52 years) at baseline. In the sample, 42.6% had a bachelor's degree or higher and 36.3% self-rated their health as "very good" at baseline; 23.9% had hypertension, 43.7% had ISH, 13.5% had IR, and 4.6% had diabetes at baseline. Hypertension occurred a median of 5.0 years (95% CI, 5.4-5.5 years) earlier and metabolic outcomes (diabetes and IR) a median of 11.3 years (95% CI, 9.7-12.9 years) earlier for Black and Hispanic women vs White women; ISH occurred a median of 7.7 years (95% CI, 7.3-8.1 years) earlier for Black women vs White women. Adjustment for selection was associated with a mean 20-year decrease in estimated median age at onset, with greater decreases among Black and Hispanic women. In this multiracial cohort of midlife women, failure to account for selection biases, especially at study onset, was associated with falsely high estimates of age at cardiometabolic onset, with greater misestimation among Black and Hispanic women. The results suggest that hypertension and metabolic interventions, particularly for Black and Hispanic women, should be targeted to women aged as young as 30 years for hypertension and 40 years for metabolic interventions. Considering the timing of disease and fully addressing inherent selection biases in research are critical to understanding aging and disease risk, especially for racial and ethnic minoritized populations.

Home management of pediatric sulfonylurea ingestions

Introduction Sulfonylureas are oral antidiabetic medications that act by stimulating insulin release from pancreatic beta cells. Unintentional pediatric ingestions may result in hypoglycemia. While guidelines often recommend up to a 24-hour hospital observation period for any ingestion, the Oregon Poison Center has historically managed select patients at home. This study aimed to describe outcomes of home-managed pediatric sulfonylurea exposures and characteristics of ingestions that are appropriate for home monitoring. Methods This is a retrospective chart review of pediatric (≤5 years) sulfonylurea ingestions in a single poison center over a 19-year period (2002–2020). We reviewed 491 individual cases for age, ingestion quantity, witnessed or unwitnessed ingestions, hypoglycemia (<60 mg/dL), disposition, and severe events (seizures or coma). We excluded cases in which missing pills were later found or another agent was identified. Results Of 474 patients meeting inclusion criteria, 135 (28%) were initially managed at home. Of these, 115 (85.3%) were ingestions of ≤1 tablet, where 68 (59%) were witnessed and 47 (41%) were unwitnessed. One hundred twenty five (92.6%) of these patients were successfully monitored at home, with 10 (7%) ultimately referred to a healthcare facility (HCF). Symptoms of hypoglycemia, measured glucose on home meter <60 mg/dL, fluctuations in monitored glucose, or parental concern were indications for HCF referral. Of those referred, 5 (4%) developed uncomplicated, asymptomatic hypoglycemia. Two of these received octreotide, at the discretion of the treating physician. No patients developed seizures or coma. Discussion We report 135 pediatric sulfonylurea ingestions managed with initial home monitoring, the majority of which were successfully monitored at home without any reported adverse events. Ten patients “failed home monitoring,” as defined by referral to a healthcare facility. Of these, five developed hypoglycemia, though no patients developed symptoms or serious adverse events. Conclusion Our findings support home observation for children ≤5 years with small ingestions of second-generation sulfonylureas.

Ethnic and socioeconomic disparities in initiation of second-line antidiabetic treatment for people with type 2 diabetes in England: A cross-sectional study.

To assess any disparities in the initiation of second-line antidiabetic treatments prescribed among people with type 2 diabetes mellitus (T2DM) in England according to ethnicity and social deprivation level. This cross-sectional study used linked primary (Clinical Practice Research Datalink) and secondary care data (Hospital Episode Statistics), and the Index of Multiple Deprivation (IMD). We included people aged 18 years or older with T2DM who intensified to second-line oral antidiabetic medication between 2014 and 2020 to investigate disparities in second-line antidiabetic treatment prescribing (one of sulphonylureas [SUs], dipeptidyl peptidase-4 [DPP-4] inhibitors, or sodium-glucose cotransporter-2 [SGLT2] inhibitors, in combination with metformin) by ethnicity (White, South Asian, Black, mixed/other) and deprivation level (IMD quintiles). We report prescriptions of the alternative treatments by ethnicity and deprivation level according to predicted percentages derived from multivariable, multinomial logistic regression. Among 36 023 people, 85% were White, 10% South Asian, 4% Black and 1% mixed/other. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by ethnicity were 21% (95% confidence interval [CI] 19-23%), 20% (95% CI 18-22%), 19% (95% CI 16-22%) and 17% (95% CI 14-21%) among people with White, South Asian, Black, and mixed/other ethnicity, respectively. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by deprivation were 22% (95% CI 20-25%) and 19% (95% CI 17-21%) for the least deprived and the most deprived quintile, respectively. When stratifying by prevalent cardiovascular disease (CVD) status, we found lower predicted percentages of people with prevalent CVD prescribed SGLT2 inhibitors compared with people without prevalent CVD across all ethnicity groups and all levels of social deprivation. Among people with T2DM, there were no substantial differences by ethnicity or deprivation level in the percentage prescribed either SGLT2 inhibitors, DPP-4 inhibitors or SUs as second-line antidiabetic treatment.