Oral Antidiabetic Research Articles

Evaluating the appropriateness and the factors associated with sodium-glucose co-transporter 2 inhibitors prescribing in a Middle Eastern country: a cross-sectional study.

Sodium glucose co-transporter 2 inhibitors (SGLT2is) are a novel class of oral antidiabetic drugs (ADDs). Studies evaluating the appropriateness of SGLT2is prescribing, and the factors associated with their initiation in the Middle East region are lacking. This study aimed to evaluate the appropriateness of prescribing SGLT2is based on indication, dosing, and contraindication and determine the factors associated with their initial prescribing. In this cross-sectional study, a cohort of 650 patients newly prescribed SGLT2is (n = 400) and/or any other oral ADDs (n = 250) during 2020 were included. Data were extracted from an electronic medical record system. Multivariate logistic regression was conducted to investigate factors associated with prescribing SGLT2is. SGLT2is were prescribed for appropriate indication in 400 patients (100%), while inappropriately prescribed in relation to contraindication and dosing in 14 patients (3.5%). Male patients were more likely to be prescribed SGLT2is (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.02-2.82). Patients with a baseline glycated hemoglobin (HbA1c) above 7% and atherosclerotic cardiovascular disease (ASCVD) were more likely to be prescribed SGLT2is (OR, 3.22; 95% CI, 1.84-5.64) and (OR, 2.18; 95% CI, 1.05-4.52), respectively. Patients receiving metformin (OR, 7.56; 95% CI, 4.46-12.80), sulfonylureas (OR, 2.30; 95% CI, 1.16-4.56), and dipeptidyl peptidase 4 inhibitors (OR, 3.43; 95% CI, 2.00-5.87) were more likely to be prescribed SGLT2is. SGLT2is were found to be typically prescribed for the appropriate indication. Among the most important factors associated with prescribing SGLT2is are having uncontrolled HbA1c, history of ASCVD, and using other ADDs.

Dapagliflozin Suppresses High Glucose-Induced Proliferation, Oxidative Stress, and Fibrosis by Reducing Mettl3-Induced m6A Modification in Marcks mRNA.

Diabetic cardiomyopathy (DCM) is a common and severe complication of Diabetes mellitus (DM). Dapagliflozin (DAPA) is an oral anti-diabetic drug worldwide for the treatment of type 2 DM. However, the action and mechanism of DAPA in cardiac fibrosis during DCM remain vague. Primary cardiac fibroblasts (CFs) were incubated with high glucose (HG) in vitro. Cell proliferation was detected by MTT and EdU assays. Oxidative stress was evaluated by determining the production of reactive oxygen species and malondialdehyde. Cell fibrosis was assessed by detecting fibrosis-related proteins by western blotting. Levels of Mettl3 (Methyltransferase 3) and Marcks (myristoylated alanine-rich C kinase substrate) were measured using qRT-PCR and western blotting. The m6A modification profile was determined by methylated RNA immunoprecipitation assay and the interaction between Mettl3 and Marcks was verified using dual-luciferase reporter and RIP assays. DAPA treatment alleviated HG-induced proliferation, oxidative stress, and fibrosis in CFs. HG promoted the expression of Mettl3 in CFs. Knockdown of Mettl3 reversed HG-induced proliferation, oxidative stress, and fibrosis in CFs; moreover, forced expression of Mettl3 abolished the protective effects of DAPA on CFs under HG condition. Mechanistically, Mettl3 interacted with Marcks in CFs and induced Marcks mRNA m6A modification. HG induced high expression of Marcks in CFs. The overexpression of Marcks could counteract DAPA or Mettl3 knockdown-evoked inhibitory effects on CF proliferation, oxidative stress, and fibrosis under HG condition. Dapagliflozin suppressed HG-induced proliferation, oxidative stress, and fibrosis by reducing Mettl3-induced m6A modification in Marcks mRNA.

A SYSTEMATIC REVIEW ON ADHERENCE TO ORAL ANTIDIABETIC DRUGS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world and one of the main reason for this is poor adherence to oral anti-diabetic drugs, which can lead to therapy failure and increase risk of complications. So we planned this systematic review with an aim to get an adherence estimation to oral anti-diabetic drugs in type 2 diabetes mellitus patients for which a literature search was performed in pubmed, Google Scholar, scopus, and central databases to find observational studies on therapeutic adherence in users of oral anti-diabetic drugs. Our analyses showed that adherence rate to oral anti-diabetic drugs therapy ranged from 23 to 90%. This review confirms that many patients for whom diabetes medication was prescribed were poor compliers with treatment of oral anti-diabetic drugs.

Deprescribing oral antidiabetics in elderly patients: Do electronic leaflets across the world address it?

Diabetes caused 6.7 million deaths in 2021, equating to one death every five seconds, with its global financial burden projected to rise from $1.32 trillion in 2015 to $2.12 trillion by 2030. Severe hypoglycemia necessitates interventions like deprescribing, behavioral strategies, and technology for prevention. Deprescribing aims to reduce unnecessary medication use, enhance rational prescribing, prevent prescribing cascades, and improve health outcomes in elderly patients. Evaluating electronic leaflets can support deprescribing based on patient-centered care and shared decision-making. ObjectiveTo analyze information on deprescribing in oral antidiabetic leaflets from national medicines regulatory authorities, focusing on elderly patients with type 2 diabetes. MethodsThis documental study analyzed electronic leaflets of oral antidiabetics from the official websites of nine Medicines Regulatory Authorities: Australia, Brazil, Canada, New Zealand, Singapore, South Africa, UK, USA, and EU, covering drugs listed in the WHO's Essential Medicines List 2023. The analysis focused on the alignment of deprescribing information with the Ontario deprescribing algorithm for oral antidiabetics developed by the Bruyère Institute in Canada. ResultsOut of 72 expected leaflets, 64 (88.9 %) were retrieved. Only 18 leaflets (28.1 %) explicitly discussed deprescribing oral antihyperglycemics. Hypoglycemia and drug interaction risks were addressed in 55 leaflets (85.9 %). Caution for use in patients over 65 was mentioned in 32 leaflets (50 %), and 23 leaflets (35.9 %) addressed the risks of tight glucose and HbA1c targets. ConclusionDespite a high retrieval rate, 11.1 % of leaflets were missing, and those available contained inconsistent deprescribing information. There are significant disparities in guidance across regulatory authorities. Standardized, updated leaflets that address deprescribing in frail older patients could enhance prescribers' confidence and support shared decision-making

Long-term outcome of diabetic patients after unprotected left main percutaneous coronary interventions

Abstract Background Diabetes mellitus (DM) represents an elevated risk in terms of percutaneous coronary intervention (PCI), especially in patients with significant left main (LM) disease. Purpose Our aims were to investigate the 60-month mortality and event-free survival of consecutive patients with DM undergoing unprotected LM PCI at our centre and sought to determine the independent predictors of event-free survival. Methods We included all patients undergoing unprotected LM PCI at our tertiary care centre between 1 January 2007 and 31 December 2014. The primary endpoint was the composite of all-cause mortality, myocardial infarction, and target lesion revascularization at 60 months. Survival curves were constructed using the Kaplan-Meier non-parametric estimator. ROC analysis was used to investigate the predictive power of conventional risk scores (SYNTAX, SYNTAX II, EuroSCORE II, additive and logistic EuroSCORE, ACEF, GRACE 2). Independent predictors were determined by univariate and multivariate analysis. Results A total of 513 patients (mean age 68 ± 12 years, 64% male) underwent unprotected LM PCI during this period, among these 310 (60%) were non-diabetic (non-DM) and 203 (40%) were diabetic (DM). In terms of indication, 157 (31%) elective and 356 (69%) acute LM PCI were performed. There was no significant difference between the non-DM and DM groups in terms of acute indication (218 (70%) vs. 138 (68%), p=0.574). Within the DM group, 135 (67%) were treated with oral antidiabetics (OAD) and 68 (33%) were treated with insulin (IDM). The mean survival (34.6 vs. 39.7 vs. 43.1 months, p=0.003) and event-free survival (29.3 vs. 34.7 vs. 39.3 months, p=0.001) were significantly lower in the IDM and OAD groups compared to non-DM, respectively. Of the risk scores, the SYNTAX score was the most predictive in diabetic patients (AUC=0.767). Based on the SYNTAX score, diabetic patients with a low SYNTAX score (<23) had less events (59% vs. 66%, p=0.043) than those having a moderate/high SYNTAX score (≥23). LVEF (HR 0.976; 95% CI, 0.965-0.987, p<0.001), right coronary artery occlusion (HR 2.031; 95% CI, 1.346-3.064, p=0.001), acute coronary syndrome (HR 1.861; 95% CI, 1.252-2.767, p=0.002), use of FFR (HR 0.481; 95% CI, 0.265-0.871, p=0.016), true bifurcation lesion (HR 1.559; 95% CI, 1.068-2.277, p=0.021) and newer DES generation (HR 0.706; 95% CI, 0.568-0.877, p=0.002) were predictors of event-free survival in diabetics by univariate analysis. Glomerular filtration rate (HR 0.982; 95% CI, 0.973-0.991, p<0.001) emerged as an independent predictor according to multivariate analysis. Conclusion Consecutive diabetic patients with significant unprotected LM stenosis have poor long-term outcome after LM PCI. Anatomical complexity of the lesions is a significant predictor of event-free survival. Careful intervention planning and the use of appropriate tools can improve the outcome in this high-risk population.

Intra-Tracheal Migration of the Tracheotomy Cannula: A Case Report

Tracheotomy is a lifesaving procedure often performed by intensivists and emergency physicians. Depending on the indication for its performance, it can be either temporary or permanent. In the latter case, the use of a tracheotomy cannula can expose the patient to numerous and severe complications. We present a very rare case of a 65-year-old diabetic on oral antidiabetics, operated 7 years ago for laryngeal carcinoma and has since been carrying a short MG Krishaber-type tracheotomy cannula. The patient was admitted to the emergency department reporting intra-tracheal migration of his cannula after he had used scissors to separate the collar from the cannula due to discomfort. Thus, it was successfully extracted using the flexible bronchoscope. The patient was discharged with a new cannula and was sensitized to the importance of consulting his doctor for any complications, discomfort, or issues with the cannula.

SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients With Type 2 Diabetes.

Despite the mechanistic potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) to improve neurologic outcomes, the efficacy of SGLT2i in neurodegenerative disorders among patients with type 2 diabetes is not well established. This population-based cohort study aimed to investigate the association of SGLT2i use with risks of incident dementia and Parkinson disease (PD) in patients with type 2 diabetes. This was a retrospective examination of data from a cohort of 1,348,362 participants with type 2 diabetes (≥40 years), who started antidiabetic drugs from 2014 to 2019, evaluated using the Korean National Health Insurance Service Database. Propensity score matching (1:1; SGLT2i to other oral antidiabetic drugs [OADs]) produced a cohort of 358,862 participants. Primary outcomes were the individual incidence of Alzheimer disease (AD), vascular dementia (VaD), and PD. Secondary outcomes were all-cause dementia (AD, VaD, and other dementia) and a composite of all-cause dementia and PD. Cox proportional hazards models were used to investigate the association between SGLT2i use and the risks of dementia and PD. From the 358,862 participants analyzed (mean [SD] age, 57.8 [9.6] years; 58.0% male), 6,837 incident dementia or PD events occurred. Regarding the individual endpoints, SGLT2i use was associated with reduced risks of AD (adjusted hazard ratio [aHR] 0.81, 95% CI 0.76-0.87), VaD (aHR 0.69, 95% CI 0.60-0.78), and PD (aHR 0.80, 95% CI 0.69-0.91) with a 6-month drug use lag period. In addition, use of SGLT2i was associated with a 21% lower risk of all-cause dementia (aHR 0.79, 95% CI 0.69-0.90) and a 22% lower risk of all-cause dementia and PD than use of other OADs (aHR 0.78, 95% CI 0.73-0.83). The association between the use of SGLT2i and the lowered risk of these neurodegenerative disorders was not affected by sex, Charlson Comorbidity Index, diabetic complications, comorbidities, and medications. Sensitivity analysis further adjusting for bioclinical variables from health screening tests, including blood pressure, glucose, lipid profiles, and kidney function, yielded generally consistent results. In this nationwide population-based study, SGLT2i use significantly reduced the risks of neurodegenerative disorders in patients with type 2 diabetes independent of various factors including comorbidities and bioclinical parameters. This study provides Class II evidence that SGLT2 antidiabetic drugs decrease the risk of dementia and PD in people with diabetes.

Serum interleukin-10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase-4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i-related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i-unrelated BP, 17 patients with DPP4i-related BP, and 13 healthy controls were analyzed. Patients with DPP4i-related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)-erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti-BP180 antibody than patients with DPP4i-unrelated BP. The serum interleukin (IL)-6 level was significantly higher in patients with DPP4i-related BP than in healthy controls (P = 0.0037). The serum IL-10 level was significantly higher in patients with DPP4i-related BP than in patients with DPP4i-unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI-blister/erosions score (r = 0.757, P = 0.001), BPDAI-erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI-total score (r = 0.833, P < 0.001) in patients with DPP4i-related BP. In conclusion, patients with DPP4i-related BP had increased serum levels of IL-6 and IL-10 compared with healthy controls and positive correlations between the serum IL-10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL-10 level is a potential objective biomarker of disease severity in patients with DPP4i-related BP.

7199 Characterization of patients with type 2 diabetes who relied on sulfonylureas for glycemic control

Abstract Disclosure: J. Jang: None. Y. Yang: None. H. Jang: None. S. Moon: None. S. Min: None. S. Lee: None. K. Park: None. H. Jung: None. Gliptins have substituted sulfonylureas (SU) in patients people with type 2 diabetes (T2D). However, in some patients, stopping SU was impossible due to abrupt glycemic deterioration. We have described this subset of patients as ‘SU-dependent patients’ by a retrospective study: they had maintained HbA1c ≤ 7% for ≥ 6 mo with a low-dose SU, while discontinuation of the SU unexpectedly increased HbA1c, and resumption of the SU recovered by resuming SU. This study aimed to prove the “SU-dependent patients” by a prospective design, and to analyze the clinical and genetic characteristics potentially associated with the response to SU. The study recruited 58 patients whose HbA1c levels were &amp;lt; 7.5% on oral anti-diabetics (OAD) including a low-dose SU (glimepiride-equivalent 2 mg/day). After obtaining informed consent, SU was replaced with another OAD, the participants were monitored for 20 wk. If the HbA1c levels deteriorated by ≥ 1.5% point, they were considered SU-dependent and resumed the previous SU (NCT04123587). In the SU-dependent patients, whole exome sequencing (WES) was performed to identify rare variants with a substantial effect size. Single nucleotide variants (SNV) were filtered using a target gene-based analysis focused on functional variants regarding insulin secretion and Asian-specific feature. Among the 58 enrolled participants, 3 withdrew their consent and resumed the SU, 5 met the criteria of SU-dependency and resumed the SU. Fifty persons did not meet the criteria for 20 wk, however, 7 of them resumed the SU thereafter. Lastly, 15 participants (26%) resumed SU within 1 year after the discontinuation, and their HbA1c returned to the baseline levels, which was comparable to that of those who did not resume SU. The 15 persons who required SU did not significantly differ from the others in the clinical features, including age, sex, BMI (24.0 vs 25.7 kg/m2, p=0.082) and the baseline HbA1c (6.9 vs 6.6%, p=0.057). According to the WES conducted on 22 SU-dependent patients (5 from the prospective study and 17 from the retrospective one), 103 SNV were filtered from 75 genes. The average allele frequency was 0.85 x 10-3 in global population, and 7.2 x 10-3 in East Asians. Notably, SNV from 9 genes were repeatedly found in both the separate studies. Several genes harbored stop-gained mutations which may induce downregulation of the gene expression, and one of them in GIPR has been validated by functional experiments (ENDO 2023, #SAT-062). Our study revealed that a portion of Korean patients with T2D are exceptionally susceptible to SU, and identified candidate variants associated with the response using WES. It may contribute to personalized therapy by screening those patients who would spend several years before taking SU, which have a low priority in general. Funding: KHIDI-AZ Diabetes Research Program, SNUH fund (0420190600), and NRF (2022R1A2C2004570) Presentation: 6/2/2024

6938 An Unusual Case of New-onset autoimmune insulin dependent Diabetes Mellitus Complicating Gestational Diabetes Mellitus in A Pregnant Female Diagnosed Early Postpartum - The Enigma of Autoimmunity and Diabetes During Pregnancy

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Gestation diabetes is the most common metabolic disorder in pregnancy affecting 25% of pregnancies. T1DM accounts for 0.2-0.5% of all pregnancies in the United States yearly. New-onset autoimmune insulin-dependent diabetes mellitus during pregnancy is very uncommon and it might be overlooked. Diabetes-related autoantibodies have been studied in women with GDM with prevalence of 0-10%. There is controversial data regarding the clinical significance of checking diabetes antibodies in pregnancy. Case Presentation: A 22-year-old G1P1 female with history of Hashimoto hypothyroidism presented during early second trimester for evaluation of GDM with serum glucose of 300s mg/dl in a random blood sample with multiple subsequent high values, hemoglobin A1C of 9.4% (prepartum value was 5.3%). Patient was started on insulin during pregnancy. Pregnancy was complicated with cesarian section and macrosomia. 1 week postpartum, A1c was 5.4%, Insulin was discontinued, and patient was continued on Metformin. 2 months Postpartum, patient presented with persistent high blood glucose values of 300-400 mg/dl with no signs of DKA. Glipizide and Glargine 15 units daily were added though patient continued to have hyperglycemia. Laboratory workup were remarkable for high blood glucose of 342 mg/dl, low C peptide of 0.6 ng/dl, and positive glutamic acid decarboxylase antibodies (GAD Ab) 38.8 U/ml. oral antidiabetics were discontinued and prandial insulin was added. Discussion: GDM is a risk factor for DMII after pregnancy given high insulin resistance postpartum, Data regarding new-onset DMI and diabetes autoimmunity during pregnancy is lacking. About 0-10% of women with gestational diabetes develop DM autoantibodies. GAD Ab exhibits the highest sensitivity of 63% for type 1 diabetes prediction compared to Islet cell antibodies (48%), and tyrosine phosphatase-related islet antigen 2 (34%). Pathophysiology of autoimmune DM during pregnancy is not quite understood; It is thought that when autoimmune tendency is present, GDM causes β-cells to deteriorate due to excessive insulin production in setting of insulin resistance, and the burden of third-trimester gestation may cause the insulin deficiency to be expressed sooner than non-pregnant female. So far, Literature about the predictive value or specific clinical features of checking diabetes autoantibodies is discordant and inconclusive. It is suggested to screen for autoantibodies only when array of clinical hallmarks suggestive of an autoimmune DM form of GDM present as young age, low BMI, need for insulin therapy early in pregnancy, presence of ketones, concurrent other autoimmune conditions (e.g., thyroiditis). This case is to shed light on autoimmunity in pregnancy. More data is needed with longer follow-up to better identify women at risk, their characteristics, indications for autoantibodies testing, follow and prognosis. Presentation: 6/2/2024

IGlarLixi effectively reduces residual hyperglycaemia in Chinese people with type 2 diabetes on basal insulin: A post hoc analysis of the LixiLan-L-CN study.

To compare the effects of iGlarLixi versus insulin glargine 100 U/mL (iGlar) on residual hyperglycaemia in Chinese people with uncontrolled type 2 diabetes (T2D) on prior basal insulin (BI) therapy ± oral antidiabetic drugs in the LixiLan-L-CN study (NCT03798080). In this post hoc analysis, residual hyperglycaemia (i.e. HbA1c ≥ 7.0% [≥ 53 mmol/mol] and fasting plasma glucose [FPG] < 7.0 mmol/L) were assessed over 30 weeks. Outcomes were assessed at week 30 in participants with baseline residual hyperglycaemia, including changes from baseline in HbA1c, FPG, 2-hour postprandial glucose (PPG) and daily BI dose, the proportion of participants with HbA1c less than 7.0% (< 53 mmol/mol) and FPG less than 7.0 mmol/L and the incidence of hypoglycaemia. Of 421 participants, 124 (29.5%) had baseline residual hyperglycaemia (iGlarLixi, n = 64 [31.7%]; iGlar, n = 60 [29.1%]). At week 30, the residual hyperglycaemia rate decreased to 7.0% with iGlarLixi and increased to 43.3% with iGlar. Among participants with baseline residual hyperglycaemia, a greater proportion achieved both HbA1c and FPG targets at week 30 with iGlarLixi versus iGlar (43.8% vs. 16.7%), and iGlarLixi provided greater reductions in HbA1c (least squares mean [LSM] difference, -0.9% [-9.4 mmol/mol]) and 2-hour PPG (LSM difference, -4.7 mmol/L; both P < .001). Daily BI dose and incidence of hypoglycaemia were similar in the two groups. The findings of this post hoc analysis suggest that iGlarLixi had greater benefits than iGlar in reducing the rate of residual hyperglycaemia over 30 weeks in Chinese people with suboptimally controlled T2D on prior BI-based therapy.

A Long-Term Retrospective Real-World Evidence to Understand the Pattern of Insulin Prescription in Patients with Type 2 Diabetes Mellitus: Evaluating the Role of Insulin Initiation

Abstract Aims and Objective: To evaluate the prescription pattern of insulin and oral antidiabetic drugs (OADs) and the trend of glycemic control in people with diabetes (PwD) with type 2 diabetes mellitus attending a tertiary care center in India. Materials and Methods: This retrospective, cross-sectional observational study included clinic records of 647 PwD collected at three different time points (2011, 2015, and 2019). Population characteristics, patterns of glycemic parameters, and trends of antidiabetic medication were analyzed. Results: PwD population was similar in terms of anthropometric and clinical variables. Dysglycemia was observably higher in the 2015 population (mean HbA1C = 8.37 ± 1.8%) compared with the 2011 population (6.4 ± 0.4%) and stabilized in the 2019 population (8.35 ± 1.9%) compared with the 2015 population. This correlated with the trend of increase in basal and bolus insulin prescriptions as more subjects were initiated on insulin to address the higher dysglycemia in 2015 than in 2011 and were later titrated in 2019. The proportion of subjects with uncontrolled diabetes increased marginally in 2015 (50.9%) compared with 2011 (45.6%) and decreased significantly in 2019 (34.1%) compared with 2015. This correlated with the additive increases of premix insulin, sodium-glucose transport protein 2 inhibitors (SGLT2i), and dipeptidyl peptidase 4 inhibitors (DPP4i) prescriptions. Conclusion: We observed a judicious usage of insulin prescriptions correlating with the higher need for PwD to be initiated with basal insulin to counter the increasing trend of dysglycemia, followed by more premix insulin prescriptions to address stabilized dysglycemia. Optimal diabetes control can be partly attributed to dysglycemia stabilization by insulin initiation and usage of newer OADs, such as SGLT2i and DPP4i.

Exploring disparities: A comparative analysis of insulin-naïve, regular users, and inertia patients among type 2 diabetes mellitus outpatients in India

ABSTRACT Introduction: Insulin utilization pattern varies greatly in type 2 diabetes mellitus (T2DM) patients. Clinical inertia in treatment intensification hinders glycemic control in T2DM management. This study investigated insulin prescription trends and various predictors among insulin naive, user, and insulin inertia (II) patients in T2DM. Methodology: A retrospective analysis of T2DM patient records from the diabetes clinic at a tertiary care center was conducted. Data on socio-demographics, anthropometry, disease characteristics, comorbidities, adherence, and medication prescribing patterns were collected. Analysis was done using tests of significance, odds ratio (OR), and multivariate logistic regression. Results: A total of 950 records were analyzed, with 17.3% of patients identified as insulin users (IU), 70.9% being insulin-naïve (IN), and 11.8% having II. IUs had significantly higher glycemic levels including HbA1c, fasting, postprandial, and random blood sugars compared to the other groups. Higher HbA1c levels were associated with significantly increased odds of insulin usage (OR: 3.46, confidence interval (CI): 1.94–6.16), while individuals taking sulfonylureas had lower odds of insulin usage (OR: 0.27, CI: 0.08–0.91). A significant association was also seen with the total number of oral antidiabetic drugs prescribed (four drugs; OR: 15.6, and five drugs; OR: 9.1). Other factors did not show a significant association. The regression model showed HbA1c level as low as 7.9% could indicate a future insulin requirement in 22% of patients. Conclusion: The study outlines differences in characteristics and parameters among T2DM patients who require or do not require insulin and highlights the challenges in insulin initiation in Indian T2DM patients. Findings on II underscore the need for timely treatment intensification.

Proportion of Hip Fracture and the Associated Risk Factors among Egyptian Females

Abstract Background Fragility fractures caused by osteoporosis are well-known to increase the risk of further fragility fractures; a history of the wrist, vertebral body, or hip fractures increases the risk of further fractures accordingly. Fragility fractures induce lower activities of daily living, and repeated fractures further reduce mobility. Aim of the Work The objective of this study was to identify the proportion of hip fracture among Egyptian females and its associated risk factors, and also to identify the proportion of hidden vertebral fractures among those with fragility hip fractures. Patients and Methods To assess the proportion of fragility hip fractures among males aging 40 years and older we collected the cases of fragility hip fractures presented to orthopedic emergency room during the period from January 1, 2019 to December 31, 2020, excluding those with high impact fractures or pathological fractures. Results Assessment of the anthropometric measures revealed groups differed significantly in the BMI. Assessment of the geriatric depression scale (GDS), mini mental state examination (MMSE), and mini nutritional assessment (MNA) in the two groups demonstrated that the patient's group had significantly higher score in GDS suggestive of depression, and significantly lower score in MMSE and MNA suggestive of associated dementia and malnuitrition respectively. Also evaluation of the prevalence of chronic diseases revealed that patient's group had significantly higher prevalence of diabetes mellitus, higher intake of oral antidiabetics, higher prevalence of dementia, chronic kidney disease. Medical history assessment demonstrated that patient's group were more prevalently using steroid and antiepileptics. GDS, MMSE, and MNA had a diagnostic value for hip fractures predictors of hip fractures highlighted that significant predictors were older age, marital status, low BMI, smoking, depression, poor nutritional status, DM, dementia, CKD, and oral steroids intake. Conclusion Osteoporosis is a complex and costly disease, osteoporotic fractures may be largely preventable, as environmental factors are open to intervention, and effective pharmacological agents are available. From both clinical and economic perspectives, aggressive measures to detect osteoporosis at earlier stages may be warranted.

Various Approaches and Future Prospective for Therapies for Diabetes: A Review

The global prevalence of diabetes mellitus disease marked by increased blood glucose levels, has reached epidemic proportions. This review provides a comprehensive assessment of the current landscape of diabetes therapies and outlines future prospects for improving the management and treatment of this condition. The current scenario highlights a multifaceted approach to diabetes management, with a focus on lifestyle interventions, oral antidiabetic drugs, insulin therapy, and emerging technologies like continuous glucose monitoring and closed-loop systems. While these approaches have significantly improved the lives of people with diabetes, several challenges persist. These include medication adherence, hypoglycemia risk, and the financial burden of diabetes care. Innovative treatments that improve glucose regulation, improve cardiovascular health, and help patients lose weight—like SGLT-2 inhibitors and GLP-1 receptor agonists—have showed promise in treating these issues. The future prospects for diabetes therapies are exciting, with ongoing research into cell-based therapies, including pancreatic islet transplantation and stem cell-derived beta cells. Personalized medicine approaches, driven by genetics and artificial intelligence, hold the potential to optimize treatment regimens and predict individual responses to various therapies. Furthermore, advancements in telemedicine and digital health technologies will enhance patient self-management and remote monitoring.

Metformin – the old drug with new therapeutic possibilities

Original Article, Pol J Public Health, Vol. 134 (2024): 47-51 Paulina Oleksa, Kacper Jasiński, Daria Żuraw, Mateusz Sobczyk, Monika Żybowska, Anna Rzewuska-Fijałkowska, Karolina Haczkur-Pawłowska, Piotr Więsyk Students’ Scientific Society at the Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Poland Introduction. Metformin is an oral antidiabetic drug from the biguanide group, popularly referred as an aspirin of the 21st century. The therapeutic targets of metformin are expanding. It is characterized by antineoplastic, immunoregulatory, anti-aging and neuroprotective properties. We aimed to evaluate the pleiotropic effects of metformin, taking into account its different mechanisms, efficacy and safety in contemporary public health challenges. Material and methods. We conducted the literature review from 2014 to 2024 using the PubMed and Google Scholar. Results. Metformin, depending on the cancer and its stage, enhances the cancer treatment effects, prevents the drug resistance, lengthens overall time of survival, reduces the risk of recurrence. In the Parkinson’s disease, Alzheimer’s disease and depression metformin can even increase the risk of their occurrence, especially in high doses. Such doses predispose to the cobalamin deficiency, affecting the functioning of the nervous system. Metformin was effective in seizure control of epilepsy. It has positive impact on the course of some autoimmunological diseases. Among diabetics treatment, outcomes of COVID-19 and tuberculosis could be improved by metformin. Conclusions. Metformin is pluripotential drug. Possibilities of adjuvant metformin therapy are very promising, but it cannot be recommended as standard treatment. This issue requires further investigation, preferentially randomized controlled trials on the bigger research samples. Keywords: metformin and therapy, metformin and treatment, metformin and advances.

The use of Oral Anti-Diabetic Medications in Diabetes Mellitus type 1: An Educational Article and Expert Opinion

Diabetes mellitus type 1 is lifelong condition resulting from failure of production of insulin because of the loss of pancreatic islet beta-cells because of autoimmune damage. Patients with this type of diabetes need lifelong treatment with insulin to remain alive. Poor diabetic control which predisposes to a variety of complications is not uncommon in patients treated with insulin alone. Therefore, the use of medications that can possibly enhance the therapeutic effect of insulin and reduce the risk of diabetic complications has been considered. Oral anti-diabetics including acarbose, an inhibitor of intestinal α-glucosidase, metformin, a biguanide, sulfonylureas including glipizide, and sitagliptin, an inhibitor of dipeptidyl peptidase 4 (DPP-4) are primarily used for the treatment of non-insulin dependent diabetes (Type 2). The aim of this paper is to provide an overview of the use of oral anti-diabetics in the treatment of insulin dependent diabetes (Type 1). Expert opinion: The current evidence-based expert opinion recommends the judicious use of oral anti-diabetics especially acarbose and metformin in the treatment of unsatisfactorily controlled insulin dependent diabetes type 1. These medications can help in improving diabetic control through reducing glucose levels after meals, and can contribute to lowering the levels of glycosylated hemoglobin (HbA1c). The use of these oral anti-diabetics can also help in reducing insulin requirement.

STATISTICAL RESEARCH ON THE CORRELATION BETWEEN BMI AND GLYCOSYRED HEMOGLOBIN IN PATIENTS WITH DIABETES

Diabetes is a significant global challenge to the health and well-being of people, families and countries. The main objectives of this research are: to statistically determine the correlation between BMI and the value of glycated hemoglobin (HbA1c) and to analyze the eating habits and lifestyle of the 109 subjects who were included in this study. The research was conducted in the period from 01.06.2023-30.06.2023. by the Faculty of Food Technology and Nutrition at the University of Tetovo and VT Diet Club - Bitola. The data from the 109 respondents (35 men and 74 women) aged from 5 to 81 years. were collected by an online questionnaire. Information about minors was obtained from their parents - guardians. The following statistical methods were used: Pearson's correlation coefficient and relative numbers. 68% of the respondents suffer from diabetes type 2, and 32% of the respondents suffer from diabetes type 1. Most of the patients with diabetes (29.4%) are aged 45-54 years. The value of the correlation coefficient r = 0.04 indicates that there is a very weak correlation between BMI and the value of glycated hemoglobin. This means that the value of glycated hemoglobin is influenced by other factors such as: diet, physical activity, use of therapy with oral antidiabetics and/or insulin, etc. 41.3% of respondents are overweight (BMI = 25-29.9 kg/m2), and the same percentage of respondents are obese (BMI = 30 and more kg/m2). Crucial negative food habits practiced by the respondents are: 69% of the respondents indicated that they have 3-4 meals a day (diabetics should have 3 main meals and 2 snacks) and the same % of respondents indicated that they consume food with a high glycemic index. From this study, it can be concluded that a healthy and balanced diet and physical activity are crucial for leveling glycemia in diabetics, as well as for the prevention of complications caused by diabetes.

Estimating the economic impact of blister-packaging on medication adherence and health care costs for a Medicare Advantage health plan.

Medication nonadherence is a persistent challenge in the United States, leading to increased health care resource utilization (HCRU) and health care costs and worsened health outcomes. Medicare Star Ratings is a program developed by the Centers for Medicare and Medicaid Services (CMS) to evaluate Medicare health plan quality and performance. Three of the Medicare Part D Star Ratings quality measures assess medication adherence, showing the importance CMS places on improving medication adherence in older adults. Although a variety of medication adherence-enhancing interventions are available to help promote adherence among patients, one intervention that has shown success historically is blister-packaging. To model the potential impact of blister-packaging chronic medications on HCRU and health care costs in the Medicare population. An economic model was developed to assess the potential impact of blister-packaging the 3 Medicare Star Ratings adherence measure medication classes: renin-angiotensin system antagonists (RASAs), statins, and noninsulin antidiabetics. The model perspective was that of a hypothetical Medicare Advantage health plan with a plan size of 100,000 members. A 12-month time horizon was used in the model. The dichotomous adherence threshold in the model was set at 80% or greater of the proportion of days covered (PDC). Literature-based references were used to inform both the impact of blister-packaging on the number of patients who become adherent as well as the impact of medication adherence on HCRU and health care costs for each of the medication classes. One-way sensitivity analyses and several scenario analyses were conducted to assess model uncertainty. Owing to increased adherence from the blister-packaging intervention, the hypothetical health plan in the analysis saw 776 additional members adherent to RASAs, 1,651 additional members adherent to statins, and 414 additional members adherent to oral antidiabetics. Although medication expenditure increased for all 3 medication classes (RASAs: $274,963; statins: $730,083; oral antidiabetics: $100,529), medical costs decreased across all classes (RASAs: -$4,098,848; statins: -$5,549,699; oral antidiabetics: -$917,968). Total net health care costs decreased by $3,823,885 for RASAs (-$3.19 per member per month [PMPM]), $4,819,616 for statins (-$4.02 PMPM), and $817,438 for oral antidiabetics (-$0.68 PMPM). The entire Medicare Advantage population scenario analysis saw reductions in total health care costs of $1,081,394,737 for RASAs, $1,362,987,376 for statins, and $231,171,496 for oral antidiabetics. Dispensing chronic medications with blister-packaging for Medicare Advantage health plan patients was modeled to reduce HCRU and health care costs. Future studies are needed to assess whether the impact of blister-packaging medications is tied to reductions in HCRU and health care costs in real-world settings.

Is Arterial Stiffness Interconnected with Cardiovascular Drug Prescription Patterns, Body Composition Parameters, and the Quality of Blood Pressure Regulation in Hypertensive Patients?

Arterial hypertension (AH) is a significant risk factor for cardiovascular disease and is associated with increased arterial stiffness, particularly as measured by pulse wave velocity (PWV). This study aims to explore the relationships between age groups, antihypertensive and new oral antidiabetic drugs, body composition, and arterial stiffness parameters in hypertensive patients. A single-center cross-sectional study was conducted including 584 participants who underwent 24 h ambulatory blood pressure monitoring (including central blood pressure (BP) and PWV measurement), body composition analysis, and provided medical history and current pharmacotherapy data. The study found that PWV was significantly higher in patients with poorly regulated BP in those aged 65 years and older. Significant PWV predictors included systolic BP, heart rate, peripheral mean arterial pressure, peripheral pulse pressure, augmentation index, calcium channel blockers, moxonidine, sodium-glucose co-transporter 2 inhibitors, urapidil, and statin prescription. Also, statistically significant negative correlations were found between PWV and visceral fat level, fat-free mass, and the percentage of muscle mass. The findings suggest that arterial stiffness is interconnected with peripheral and central blood pressure parameters, body composition parameters, and prescribed hypertensive and new antidiabetic drugs.