Oral Antidiabetic Research Articles

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D). This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD. Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days. The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks. In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas. The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

Physicians Perspectives on the Preference of Antihyperglycemics for the Management of Diabetes Mellitus in India

As they were commonly prescribed together for blood glucose control, metformin and more recent sulfonylureas, such as glimepiride, have been shown in numerous clinical studies to effectively reverse insulin resistance and promote insulin secretion. In India, primary care physicians and specialists used the fixed-dose combination of metformin and glimepiride in various doses. The results of clinical trials needed to be applied to regular clinical practice in the real world in order to close the knowledge gap. Regarding this, professional opinions will provide insightful information about the use of antihyperglycemics and their combinations, including their safety, effectiveness, and usefulness for a particular subgroup of patients with diabetes. So, a cross-sectional study was conducted on the prescription pattern of oral anti-diabetic drugs for patients with diabetes mellitus. The choice of oral anti-diabetic agents for diabetic patients with comorbidities was analysed by using 26 questions. About 845 physicians participated in the survey by sharing their opinions/views on the questionnaire. Also, 400 physicians out of 845 prefers glimepiride and metformin as the preferred combination to achieve the targeted glycated haemoglobin level. Moreover, 723 physicians out of 845 experienced glycated haemoglobin reduction with glimepiride and metformin for more than 3 years. Maximum glycated haemoglobin reduction with glimepiride and metformin was 1.5%-2% by 383 physicians as per the survey. They also experienced good glycaemic control and good cardiovascular safety with glimepiride and metformin. Thus, the experts recommended glimepiride and metformin very often in elderly individuals. Glycated haemoglobin reduction was more than 3 years with glimepiride and metformin, as per the clinical experience of the experts participated in the survey. They also witnessed good glycaemic control and cardiovascular safety profile with glimepiride and metformin combination.

Effectiveness and safety of insulin glargine U-300 as compared to insulin glargine U-100 in oral antidiabetic (OAD) failure cases—record-based observational study

Effectiveness and safety of insulin glargine U-300 as compared to insulin glargine U-100 in oral antidiabetic (OAD) failure cases—record-based observational study

Association Between Pharmacological Treatment Regimens and Quality of Life Among Rural Type 2 Diabetic Patients: A Comparative Analysis in Eastern China.

Numerous studies have explored the relationship between pharmacological treatment regimens and the quality of life (QoL) of type 2 diabetes (T2D) patients. However, there is a dearth of comparative studies focusing on the QoL among rural T2D patients in China across 3 distinct pharmacological treatments: oral antidiabetic drugs (OADs), insulin therapy, and a combination of OADs and insulin. Additionally, the specific correlation between these treatment regimens and distinct dimensions of QoL remains unclear, necessitating further investigation. Data from a survey of rural T2D patients in eastern China were analyzed to calculate QoL scores for different treatment groups. Multivariate linear regression was then used to assess variations in overall QoL and specific dimensions among patients on OADs, insulin, and combined therapy. OADs were most commonly used (70.36%), followed by combined (19.47%) and insulin therapy (10.17%). Patients on OADs reported the highest overall QoL, with reduced physical discomfort, improved psychological well-being, enhanced treatment satisfaction, and fewer medication side effects. Conversely, those on combined therapy had the lowest overall QoL, primarily due to increased physical discomfort. Insulin users had moderately positive overall QoL but lower psychological well-being and treatment satisfaction, along with more adverse reactions. Disparities in QoL and its dimensions exist among rural T2D patients based on treatment regimens. Healthcare providers should prioritize support systems and interventions to help patients manage side effects of insulin and combined therapy, thereby improving their QoL.

Real-world effectiveness of iGlarLixi in individuals with T2D sub-optimally controlled on oral anti-diabetic drugs with or without basal insulin in daily practice in Saudi Arabia (EMPOWER study)

IntroductionThe prevalence of type 2 diabetes mellitus (T2DM) has increased in Saudi Arabia over recent decades, with current estimates showing that 19% of adults have T2DM. There is a need to confirm the clinical outcomes and safety of iGlarLixi in the routine clinical practice setting. MethodsA multicenter retrospective non-comparative study was conducted on 224 people with T2DM on Oral anti-diabetics (OADs) or in combination with basal insulin who initiated treatment with iGlarLixi in Saudi Arabia. Data of at least 180 days (± 30 days) before and after initiating iGlarLixi were retrieved. ResultsMean HbA1c significantly decreased after iGlarLixi start, with a mean reduction of 1.6% at six months. The mean reduction in the FPG was −38.8 (95% CI -46.5 to −31.1, p < 0.001). The weight dropped from 86.17 kg to 83.33 kg after 6 months post-iGlarLixi initiation [mean reduction = −2.86, P < 0.001]. The incidence of reported hypoglycemia, symptomatic documented and/or severe cases, decreased from 0.513 (95% CI 0.33 to 0.76) per person-year at baseline to 0.002 (95% CI 0.001 to 0.011) six months after iGlarLixi. ConclusioniGlarLixi is effective and well tolerated for improved glycemic control in patients with advanced therapy from OADs or insulin in Saudi Arabia.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Effectiveness and Safety of the Intermittently Scanned Continuous Glucose Monitoring System FreeStyle Libre 2 in Patients with Type 2 Diabetes Treated with Basal Insulin or Oral Antidiabetic Drugs: An Observational, Retrospective Real-World Study

Intermittently Scanned Continuous Glucose Monitoring (isCGM) devices are increasingly being used in patients with type 2 diabetes mellitus (T2DM) on insulin therapy for their benefits regarding disease management. Evidence of isCGM use in patients with T2DM on basal or non-insulin therapy is lacking. This study aimed at assessing the efficacy and safety of isCGM in this population. This was an observational, retrospective, real-world study enrolling patients with T2DM who were starting the use of isCGM. Data from medical records (i.e., demographics, clinical characteristics, laboratory assessments, and isCGM metrics) were collected over three time periods (baseline, 3 and 6 months). The endpoints were glycated haemoglobin (HbA1c) changes and changes in isCGM metrics as defined by the International Consensus from baseline to 3 months and 6 months. Overall, 132 patients were included (69.5% male; mean age 68.2 ± 11.0 years; mean disease duration 19.0 ± 9.4 years; 79.7% on basal insulin ±non-insulin therapy; mean baseline HbA1c 8.1% ± 1.3%). The estimated mean change in HbA1c was statistically significant at three (−0.4 ± 1.0%; p = 0.003) and six months (−0.6 ± 1.3%; p &lt; 0.0001). In conclusion, isCGM proved to be effective and safe in improving glycaemic control in patients with T2DM on basal insulin or non-insulin therapy.

Safety assessment of the SGLT2 inhibitors empagliflozin, dapagliflozin and canagliflozin during pregnancy: An ex vivo human placenta perfusion and in vitro study

Although uncontrolled hyperglycaemia during pregnancy can cause complications for both the mother and her offspring, pharmacological treatment options for gestational and type 2 diabetes in pregnancy are still limited. Empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) are three sodium glucose co-transporter 2 (SGLT2) inhibitors, a newer group of oral antidiabetics that are well established in the treatment of type 2 diabetes mellitus in non-pregnant patients. To date, no data regarding their placental transfer and safety in pregnant women are available. We performed ex vivo human placental perfusions (n = 4, term placentas, creatinine and antipyrine as connectivity controls) to evaluate the transplacental transfer of EMPA, DAPA and CANA across the placental barrier and assessed their influence on the secretion of two placental peptide hormones, leptin and β-human chorionic gonadotropin (β-hCG). We discovered that all three SGLT2 inhibitors cross the placental barrier and attained maximal foetal to maternal concentration ratios of 0.38 ± 0.09 (EMPA), 0.67 ± 0.05 (DAPA) and 0.62 ± 0.05 (CANA) within the tested 360 min. A moderate but statistically significant decrease in placental leptin – but not β-hCG – secretion was observed during perfusions with SGLT2 inhibitors, which was confirmed in experiments performed with human placental BeWo cells. SGLT2 inhibitors are able to cross the human placental barrier and seem to interfere with placental leptin production. These observations should be considered in the ongoing discussion on the optimal treatment for gestational diabetes and type 2 diabetes mellitus in pregnancy.

EFFECTS OF METFORMIN ON TNF-α RELEASE IN LIPOPOLYSACCHARIDE-INDUCED MONOCYTES IN RATS

Inflammation which is a response of immune system was demonstrated in many disorders such as atherosclerosis, hypertension, diabetes, cancer and rheumatoid arthritis. Metformin, an oral antidiabetic drug, has anti-inflammatory effect apart from blood glucose regulatory effect. However, the mechanism of its anti-inflammatory effect is not clearly understood. In this study, the effect of metformin on the release of cytokines (TNF-α and IL-6) from LPS stimulated rat mononuclear blood cells was investigated. Blood samples (5ml) were taken from healthy, male, 8-12 weeks old rats (n=5, 200-250g) through cardiac puncture under general anesthesia into sterile EDTA containing tubes. Monocytes were separated by centrifugation and were resuspended in RPMI 1640 media (3.3±0.2x105 /ml). Cells were then incubated with metformin (2.5 µM, 25 µM, 250 µM) for 2,5 hours followed by addition of LPS (100 ng/ml, 1µg/ml) for further 5 hours. After centrifugation, the supernatant was taken and TNF-α level was measured by ELISA. There was no statistically significant change in the amounts of TNF-α in the LPS + metformin groups compared to the 100 ng/ml LPS group (p&gt;0.05). In LPS+metformin groups, compared to 1 µg/ml LPS, 2.5 µM and 250 µM metformin significantly increased TNF-α levels (p0.05). The amount of IL-6 was not within measurable range in this study. In summary, metformin increased the amount of released TNF-α rather than decreased in our study.

Insulin Icodec: A Silver Lining to the Diabetic Cloud

Adequate glycaemic control is the sole way to circumvent the microvascular and macrovascular complications of diabetes mellitus. Currently, available treatment options include oral hypoglycaemic agents and insulin. Oral antidiabetic drugs are often limited in their efficacy to reduce HbA1c beyond 1-2%. It is insulin alone that can reduce HbA1c exceptionally and keep it near normal. The benchmark route of insulin administration is subcutaneous injections. However, subcutaneous insulin administration accompanies issues like pain at injection site, needle phobia, lipodystrophy, peripheral hyperinsulinemia and consequently medication non-adherence. To overcome this hurdle there has been ongoing research for basal longer acting insulins. However, these basal insulins necessitate at least one daily injection. If somehow, a basal insulin could be injected just once a week, it is logical to anticipate that this would augment medication compliance, enhance patients’ quality of life, granted that it involves minimal risk of hypoglycaemia. Insulin icodec is a novel once-a week, subcutaneously administered insulin for the treatment of diabetes mellitus. Pre-clinical as well as clinical data from all six ONWARDS trials have met their primary endpoints. If approved, insulin icodec would be the first and only once-weekly basal insulin option for individuals with diabetes, filling the lacunae created by currently available basal insulins.International Journal of Human and Health Sciences Vol. 08 No. 01 Jan’24 Page: 15-21

Effectiveness and Safety of Initiation and Titration of Insulin Glargine 300 U/mL in Insulin-Naive Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetic Drug Treatment in Turkey: The EASE Study

Effectiveness and Safety of Initiation and Titration of Insulin Glargine 300 U/mL in Insulin-Naive Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetic Drug Treatment in Turkey: The EASE Study

De-indexed estimated glomerular filtration rates for the dosing of oral antidiabetic drugs in patients with chronic kidney disease.

Introduction: Adjusting drug dose levels based on equations that standardize the estimated glomerular filtration rate (eGFR) to a body surface area (BSA) of 1.73m2 can pose challenges, especially for patients with extremely high or low body mass index (BMI). The objective of the present study of patients with CKD and diabetes was to assess the impact of deindexing creatinine-based equations on estimates of kidney function and on the frequency of inappropriate prescriptions of oral antidiabetic drugs (OADs). Methods: The prospective CKD-REIN cohort is comprised of patients with eGFR <60mL/min/1.73m2. The inclusion criteria for this study were the use of OADs and the availability of data on weight, height and serum creatinine. We compared data for three BMI subgroups (group 1 <30kg/m2; group 2 30-34.9kg/m2; group 3 ≥35kg/m2). Inappropriate prescriptions (contraindicated or over-dosed drugs) were assessed with regard to the summary of product characteristics and the patient's kidney function estimated with the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the 2021 CKD-EPI equation, the Modification of Diet in Renal Disease (MDRD) equation, the European Kidney Function Consortium (EKFC) equation, their deindexed estimates, and the Cockcroft-Gault (CG) formula. The impact of deindexing the equations was evaluated by assessing 1) the difference between the indexed and deindexed eGFRs, and 2) the difference in the proportion of patients with at least one inappropriate OAD prescription between the indexed and deindexed estimates. Results: At baseline, 694 patients were receiving OADs. The median BMI was 30.7kg/m2, the mean BSA was 1.98m2, and 90% of patients had a BSA >1.73m2. Deindexing the kidney function estimates led to higher eGFRs, especially in BMI group 3. The proportion of patients with at least one inappropriate prescription differed greatly when comparing indexed and deindexed estimates. The magnitude of the difference increased with the BMI: when comparing BMI group 1 with BMI group 3, the difference was respectively -4% and -10% between deindexed 2021 CKD-EPI and indexed CKD-EPI. Metformin and sitagliptin were the most frequent inappropriately prescribed OADs. Conclusion: We highlight significant differences between the BSA-indexed and deindexed versions of equations used to estimate kidney function, emphasizing the importance of using deindexed estimates to adjust drug dose levels - especially in patients with an extreme BMI.

Association Between Fear of Hypoglycemia and Treatment Satisfaction Among Patients With Diabetes Mellitus

Background: Treatment satisfaction is one of the main factors of assessing care quality in patients with chronic diseases. Some factors may influence treatment satisfaction and improve or impair clinical outcomes. This study aimed to determine the relationship between fear of hypoglycemia and satisfaction with treatment in patients with type 2 diabetes treated with oral antidiabetic drugs. Methods: This cross-sectional study was carried out in one of the hospitals of Qazvin Province, Iran, in 2021. The research sample was 390 patients with type 2 diabetes who used oral antidiabetic drugs, selected through convenience sampling. The data were collected using the hypoglycemic fear survey (HFS) and the diabetes medication satisfaction (DiabMedSat) questionnaire. Then, the obtained data were analyzed using the independent t-test, one-way analysis of variance, and multiple linear regression in SPSS software, version 26. Statistical significance was set at P&lt;0.05. Results: Patients’ Mean±SD age was 53.4±11.49 years, and most (57.4%) were female. Treatment satisfaction score was lower in females (β=-0.12, P&lt;0.007) and patients with diabetes complications (β=-0.138, P&lt;0.005). Patients with college education had higher treatment satisfaction (β=0.173, P&lt;0.001). Patients with very severe (β=-0.29, P&lt;0.001) or severe hypoglycemia (β=-0.157, P&lt;0.034) experienced lower treatment satisfaction than those with mild hypoglycemia. Low treatment satisfaction scores were associated with fear of hypoglycemia (β=-0.39, P&lt;0.001). Conclusion: In this study, fear of hypoglycemia was associated with a decreased level of satisfaction with treatment. As a consequence, patients with type 2 diabetes must be assessed for hypoglycemia fears and their adverse effects. Also, to prevent complications caused by not taking antihyperglycemic drugs, nursing managers and clinical nurses are recommended to prepare appropriate programs to implement psychological interventions to reduce the fear of hypoglycemia.

Improving Adherence and Reducing Health Care Costs Through Blister-Packaging: An Economic Model for a Commercially Insured Health Plan.

To model the potential clinical and economic impact of blister-packaging medications for chronic conditions on medication adherence and healthcare costs in a commercially insured population. A health economic model was developed to evaluate the potential impact of blister-packaging chronic medications for a commercially insured population. The chronic medication classes assessed were renin-angiotensin-system (RAS) antagonists, statins, non-insulin oral antidiabetics, and direct oral anticoagulants (DOACs). The model was designed to reflect the perspective of a hypothetical commercially insured health plan with 100,000 members, over a one-year time horizon. Literature-based or best available epidemiologic references were used to inform the number of patients utilizing each medication class, the impact of blister-packaging on the number of patients who become adherent, as well as the impact of medication adherence in a commercially insured population on healthcare costs for each medication class assessed. Impact on costs was measured in total net healthcare costs, as well as being stratified by medical costs and medication costs. Following the blister-packaging intervention, there were an additional 591 patients adherent to RAS antagonists, 1196 patients adherent to statins, 169 patients adherent to oral antidiabetics, and 25 patients adherent to DOACs. While pharmacy costs increased, these costs were more than offset by the reduction in medical costs. Overall, the increase in patients adherent to therapy due to blister-packaging led to a reduction in total healthcare costs of $879,312 for RAS antagonists (-$0.73 per-member per-month (PMPM)), $343,322 for statins (-$0.29 PMPM), $78,917 for oral antidiabetics (-$0.07 PMPM), and $120,793 for DOACs (-$0.10 PMPM). Blister-packaging chronic medications in a commercially insured population has the potential to reduce healthcare costs. Future research is needed to confirm these findings in real-world settings and to fully understand the clinical and economic implications of blister-packaging chronic medications.

Retrospective cohort evaluation study in terms of cardiovascular and metabolic diseases in chronic hepatitis B patients.

Chronic hepatitis B (CHB) and nucleotide analogues [entecavir (ETV) and tenofovir disoproxil fumarate (TDF)] used in its treatment have been shown to affect metabolic parameters in many studies. In this study, we aimed to investigate the effects of metabolic events associated with CHB and nucleotide analogues (NAs) used in CHB treatment on ischemic heart diseases (IHD) and cardiovascular diseases (CVD). This retrospective study was conducted between June 2022 and January 2024 with a total of 241 patients diagnosed with non-cirrhotic CHB in the gastroenterology outpatient clinic, 96 of whom did not receive hepatitis B treatment, 110 of whom received TDF, and 35 of whom received ETV treatment. Patients were evaluated in terms of metabolic, CVD, and hepatology depending on whether they received antiviral treatment or not. In our study, the triglyceride-glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) were calculated in patients to evaluate potential risk factors for CVD. Again, while the total cholesterol-to-HDL-C ratio (TC/HDL-C), which is associated with CVD\IHD, was evaluated, the '4-factor fibrosis index' (FIB-4) score, which is a non-invasive indicator of liver fibrosis, was also evaluated. Diabetes mellitus (DM), fasting blood sugar (FBS), oral antidiabetic drug (OAD) usage rate, and insulin usage rate were high in patients receiving ETV treatment. The TyG index of patients receiving ETV was higher than patients in the other group (p = 0.035; p<0.05). It was determined that the probability of detecting ETV treatment in patients with a TG/HDL-C ratio of ≥1.82 cut-off value was 4.250 times higher. The odds ratio for TG/HDL-C measurements was 4.250 (95% CI: 1.384-13.054). FIB-4 score, which is a non-invasive indicator of liver fibrosis, was found to be higher in patients receiving ETV than in other groups. In patients with CHB, a relationship was observed between markers used to predict CVD risk, such as the TyG index and TG/HDL-C ratio. The group with high levels of these two markers and a high potential for developing CVD was patients receiving ETV treatment. In this first study in the literature showing the relationship between CHB and CVD, we found that the relative risk of CVD was increased in patients using ETV.

Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances.

The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications. In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin-producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations. This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Green and High Throughput Assay Using 96-Microwell Base to Determine Metformin Hydrochloride in the Tablet Dosage Form.

Metformin (MET) is an oral antidiabetic drug widely used as the primary treatment for type 2 diabetes mellitus (T2DM). While various spectrophotometric assays exist for determining MET in pharmaceutical formulations, they often have limited throughput for quality control purposes. This study describes the validation of a 96-microwell plate spectrophotometer method using charge-transfer complexes (CTCs) with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for the quality control and detected of MET. This reaction was carried out in 96-microwell plates, and the absorbance of the colored complexes of CLA and DDQ were measured at 530 nm and 460 nm, respectively, using an absorbance microplate reader. This study aims to identify and quantify the use of a 96-microwell plate spectrophotometer analytical technique for assessing complicated formulations. The method was successfully used for the quantification of MET in the tablet dosage form. The results showed good correlation coefficients (0.996 and 0.997) with CLA and DDQ, respectively. The present method showed high precision with RSD % not exceeding 2.17%. The accuracy of the method was obtained by recovery percentage, with percentage values less than ±5%. The Analytical Greenness Metric (AGREE) was used to evaluate greenness of the assays. The result show that the microwell assay method is greenness and suitable for handling large samples on a daily used with high throughput analysis. The use of the 96-microwell-plate method is superior to the existing method in terms of simplicity of the procedure, the low economic cost, and its consumption of low amounts of reagents and organic ethanol solvent, making it an environmentally friendly method. Therefore, these advantages make them suitable and rapid alternatives method to current methods for routine metformin analysis in quality control laboratories.

Prescription pattern of oral anti-diabetic drugs in Indian clinical practice

Prescription pattern of oral anti-diabetic drugs in Indian clinical practice

The Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Atrial Electromechanical Conduction Time.

This study aims to explore the impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, a newer class of oral antidiabetic drugs, on atrial electromechanical delay (EMD) in patients with type 2 diabetes mellitus (DM). This is particularly relevant given the significantly higher incidence of atrial fibrillation (AF) in diabetic patients compared to the general population. Atrial electromechanical delay is recognized as an important factor influencing the development of atrial fibrillation. This study included 30 type 2 DM patients (53.3% female, mean age 60.07 ± 10.03 years), initiating treatment with SGLT-2 inhibitors. The patients were assessed using echocardiography at baseline and again at 6 months, focusing on basic echocardiographic parameters and atrial electromechanical delay times (EMD) measured via tissue Doppler imaging. No significant changes were observed in intra-atrial EMD times. However, significant reductions were noted in interatrial EMD times, decreasing from 15.13 ± 5.87 ms to 13.20 ± 6.12 ms (P = 0.029). Statistically significant shortening occurred in lateral pulmonary acceleration (PA) times (from 58.73 ± 6.41 ms to 54.37 ± 6.97 ms, P < 0.001), septal PA times (from 50.90 ± 6.02 ms to 48.23 ± 5), and tricuspid PA times (from 43.60 ± 6.28 ms to 41.30 ± 5.60 ms, P = 0.003). Additionally, there was a significant reduction in the E/e' ratio from 8.13 ± 4.0 to 6.50 ± 2.37 (P = 0.003). SGLT-2 inhibitors might positively influence atrial electromechanical conduction, reducing DM-related functional impairments and the risk of arrhythmias, particularly AF.

A novel class of oral, non-immunosuppressive, beta cell-targeting, TXNIP-inhibiting T1D drugs is emerging.

Diabetes treatment options have improved dramatically over the last 100 years, however, close to 2 million individuals in the U.S. alone live with type 1 diabetes (T1D) and are still dependent on multiple daily insulin injections and/or continuous insulin infusion with a pump to stay alive and no oral medications are available. After decades of focusing on immunosuppressive/immunomodulatory approaches for T1D, it has now become apparent that at least after disease onset, this by itself may not be sufficient, and in order to be effective, therapies need to also address beta cell health. This Perspective article discusses the emergence of such a beta cell-targeting, novel class of oral T1D drugs targeting thioredoxin-interacting protein (TXNIP) and some very recent advances in this field that start to address this unmet medical need. It thereby focuses on repurposing of the antihypertensive drug, verapamil found to non-specifically inhibit TXNIP and on TIX100, a new chemical entity specifically developed as an oral anti-diabetic drug to inhibit TXNIP. Both have shown striking anti-diabetic effects in preclinical studies. Verapamil has also proven to be beneficial in adults and children with recent onset T1D, while TIX100 has just been cleared by the U.S. Food and Drug Administration (FDA) to proceed to clinical trials. Taken together, we propose that such non-immunosuppressive, adjunctive therapies to insulin, alone or in combination with immune modulatory approaches, are critical in order to achieve effective and durable disease-modifying treatments for T1D.