Oral Antidiabetic Agents Research Articles

High prevalence of comorbidities in older adult patients with type 2 diabetes: a cross-sectional survey

BackgroundDiabetes is a global health problem, and its incidence and complications increase with the duration of the disease and over time. This increase in complications in older patients can lead to disability and a lower quality of life. This study aimed to investigate the rate of diabetes control and complications in older adults.MethodThis was a cross-section of an ongoing cohort of patients with type 2 diabetes mellitus (T2DM) aged 65 years and older. The clinical and laboratory characteristics of older adult patients with T2DM in good and intermediate health conditions were collected between 2010 and 2022.ResultsA total of 2,770 older adult patients with T2DM were enrolled, including 1,530(55.3%) female and 1,240 (44.7%) male participants. Metabolic syndrome, hypertension, and coronary artery disease were the most common comorbidities, affecting 1,889 (71.4%), 1,495 (54.4%), and 786 (29.2%) patients, respectively. Albuminuria was present in 626 (22.6%) patients, while retinopathy was detected in 408 (14.7%) patients, including 6% with proliferative retinopathy. Most patients were treated with oral antidiabetic agents (88.9%), with metformin being the most prescribed medication (85.6%). Statins were prescribed to 71.8% of the patients. The most prescribed antihypertensive medications were angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, prescribed to 54% and 15% of patients, respectively. The hemoglobin A1c (HbA1c) goal (HbA1c < 7.5%) was achieved in 1,350 (56.4%) patients, and the low-density lipoprotein cholesterol (LDL-C) goal (LDL < 100) was achieved in 1,165 (45.6%) patients. Blood pressure control (BP < 140/90) was achieved in 1,755 (65.4%) patients. All three goals were achieved in 278 (10.3%) patients. There were no significant differences in clinical laboratory results and the patients’ characteristics based on gender.ConclusionThe rate of progression of complications in older adult patients is higher than the effectiveness of the treatment, indicating the need for increased social support for this age group.

In-silico Assessment of Polyherbal Oils as Anti-diabetic Therapeutics.

Diabetes mellitus (DM) is characterized by elevated blood glucose levels either due to insufficient insulin production, defective insulin action, or both. It affects nearly 537 million individuals worldwide. Pharmacological treatment involves the use of oral antidiabetic agents as mono or combination therapy that effectively aids in controlling hyperglycemia. Despite providing therapeutic benefits, these medications limit their use owing to adverse side effects. Certain natural products, including essential oils, have promising anti-diabetic properties. The present study explores the effectiveness of two polyherbal oils and their compound towards the treatment of DM based on an In-silico approach to drug investigations Methods: Compounds present in the polyherbal oil formulation were identified using GCMS/ MS analysis. Selected compounds undergo molecular docking with the receptor, and proteins play an important role in DM. The potential compounds showing higher interactions than the known inhibitors or inducers were evaluated using molecular dynamic simulations RMSD value. The compounds identified through GC-MS analysis possess anti-diabetic and antiinflammatory properties. With the aid of in silico prediction methods, compounds such as geraniol, cinnamaldehyde, anethole, caryophyllene, terpinyl acetate, cymene, linalool, menthol, Phenol,2-methoxy-3-(2-propenyl), and 2,6- octadienal,3,7-dimethyl were identified as strong binders of GLUT4 and insulin receptor proteins. Geraniol and Phenol,2-methoxy-3-(2-propenyl) interaction with GLUT4 were of particular importance owing to their conformational stability. Our data suggest an agonistic effect of compounds on target proteins aiding in enhanced insulin activity and could serve as a potential anti-diabetic agent.

SITAGLIPTIN AMELIORATES ATORVASTATIN INDUCED HEPATOTOXICITY IN RATS

Atorvastatin (ATOR) is the most widely used statin for the treatment of hypercholesterolemia, which is the most common cause of severe liver injury. Sitagliptin is a selective dipeptidyl peptidase-4 inhibitor (DPP4-I) used clinically as oral anti-diabetic agent. This study aimed to identify the effect of sitagliptin (SITA) pretreatment against Atorvastatin (ATOR) induced hepatotoxicity in albino rats. Twenty-five rats were divided into five groups (5 rats in each); normal control, ATOR, SITA and two sitagliptin groups, which pretreated with sitagliptin 10 and 20 mg/kg/day in combination with ATOR 20mg /kg / day for eight consecutive days prior to ATOR. The results revealed that ATOR induced noticeable hepatic injury in the form of moderate Hepatoportal + sinusoidal congestion, all Zonal changes, moderate Cloudy swelling + hydropic degeneration, moderate Fatty change and mild Apoptosis. Biochemical analysis exposed a significant rise in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in ATOR group. Increased Proinflammatory TNF-alpha, Oxidative stress MDA and depressed antioxidant system of GSH were evident in ATOR group. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological changes induced by ATOR. In conclusion, sitagliptin ameliorated the hepatotoxicity induced by atorvastatin. This effect was probably based through suppression of inflammatory, oxidative stress and apoptotic processes. Sitagliptin might exert beneficial effect on diabetic hepatic disorders which mandate further clinical research.

Antidiabetic and Antihyperlipidemic Activity of Ethanolic Extract of Mentha viridis in Alloxan Induced Diabetic Rats

This research was designed to examine the phytochemicals of Mentha viridis (M. viridis) ethanolic extract and the antidiabetic and antihyperlipidemic activities in alloxan-induced animal models. Diabetes was induced chemically by administering a unit dose of alloxan at 120 mg/kg BW. After alloxan induction, hyperglycemic rats were dealt with ethanolic extract of leaf and whole plant, metformin, and a mixture of leaf extract with metformin and whole plant extract with metformin for two weeks. Ethanolic extract of leaf and whole plant, metformin, and a combination of both leaf and whole plant extract with metformin therapies reduced glucose levels in the blood compared with the diabetic negative control group after two weeks of treatment. However, among the therapies, the ethanolic leaf extract and the combination of whole plant extracts with metformin were found to be the most effective (p&amp;lt;0.05), with reductions of 62.82% and 72.89%, respectively. After diabetes induction, the serum level of TG (triglycerides), TC (total cholesterol), LDL-C (low-density lipoprotein-cholesterol) escalated notably (p&amp;lt;0.05), and HDL-C (high-density lipoprotein-cholesterol) level decreased remarkably (p&amp;lt;0.05) in hyperglycemic rats as opposed to healthy normal rats. Ethanolic leaf extract and a combination of whole plant extract with metformin significantly minimized the elevated extent of TG and LDL-C. They surged HDL-C, but the TC level was reduced by whole plant extract only after two weeks of treatment. The standard procedures were used to identify the phytochemical compounds of the medicinal plant M. viridis. The phytochemical compounds such as alkaloids, resins, tannins, phenols, flavonoids, steroids, and terpenoids appeared in the ethanolic leaf extract of M. viridis. The findings suggest that M. viridis might provide better glycemic control and hypolipidemic effect in diabetic rats when administered alone or combined with oral antidiabetic agents. Incorporating M. viridis extract with metformin in improving hyperglycemic and hyperlipidemic conditions in diabetic rats proves that M. viridis has a synergistic effect, which could enhance the antidiabetic activity of oral hypoglycemic agents.

NOVOS ANTIDIABÉTICOS E PERSPECTIVAS NO MANEJO DA HIPERGLICEMIA CRÔNICA

The management of type 2 diabetes mellitus (T2DM) has evolved with the emergence of new oral and subcutaneous antidiabetic agents, which aim not only at glycemic control but also at the prevention of systemic complications. This study reviews the effects of new classes of hypoglycemic agents, such as SGLT-2 inhibitors, GLP-1 agonists, and insulin analogs, on chronic hyperglycemia control and complication prevention. An integrative literature review was conducted using the PubMed database, with articles published between 2019 and 2024, selected using the search key: ‘novel antidiabetic drugs’ OR ‘SGLT-2 inhibitors’ AND ‘chronic hyperglycemia’. Clinical trials and systematic reviews with full text in English were included. SGLT-2 inhibitors were found to be effective in reducing cardiovascular and renal events, along with a significant improvement in glycemic control. GLP-1 agonists and new combination therapies also demonstrated reductions in HbA1c levels and improvements in therisk profile for complications such as cardiovascular disease, diabetic nephropathy, and retinopathy. The inclusion of new devices, such as smart pens, has also contributed to individualized patient management. The introduction of new antidiabetic agents, with innovative mechanisms of action, has brought a significant advancement in the treatment of T2DM patients, aiding in complication prevention and optimizing glycemic control. The continued evolution of these therapies promises new perspectives in disease management.

Influence of Adding Empagliflozin to Conventional Anti-diabetic Therapy on Quality of Life Scale for Type 2 Diabetic Patients

To evaluate the efficacy of empagliflozin on the quality of life (QoL) and glycemic index in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with conventional oral anti-diabetic agents (OADs). A pre-post study involved forty T2DM patients who were on a combination of three OADs (glimepiride + metformin + vildagliptin) with glycated hemoglobin A1c (HbA1c) 7.0% - 12.0%. All patients received empagliflozin (10 mg/day) as add-on therapy for 16 weeks. Adding empagliflozin showed significant reduction in postprandial plasma glucose (PPG), (HbA1c), body mass index (BMI) and index of central obesity (ICO) (p&lt;0.001). Significant improvements have been shown in the Quality of Life in Iraqi type 2 diabetic patients (QOLSID) scores post-intervention (p&lt;0.001). Besides, good QoL was reported in patients with lower BMI and among those who had DM for duration less than 10 years. The outcome of this study showed that empagliflozin as add-on to oral antidiabetic triple therapy in poorly controlled T2DM has achieved a better weight management, well glycaemic control and enhanced QoL through the therapy, and was well tolerated among the study sample. Keywords: Empagliflozin, Glycemic index, Quality of life, SGLT2 inhibitors, Type 2 DM.

Glucagon-Like Peptide-1 Receptor Agonists are Not Associated with an Increased Risk of Progressing to Vision-Threatening Diabetic Retinopathy

ABSTRACT Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. Methods A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. Results A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92–1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95–1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58–1.12, p = 0.20). Conclusion We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR.

Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds

In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both in vitro and in vivo assays. The tested compounds 7a-7j demonstrated In vitro inhibitory potential against α-glucosidase, as indicated by their IC50 values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC50 value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for in vivo evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both in vitro and in vivo, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the α-glucosidase enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.

The Analysis Study of Effects of Oral Antidiabetic Drugs on Tuberculosis Risk and Treatment Outcomes : A Comprehensive Systematic Review

Background: Diabetes mellitus triples the risk of infection, leading to poor clinical outcomes. Hyperglycemia suppresses immune responses, affecting TB and diabetes patients. Modulation of host cell responses and targeting pathogens could improve treatment outcomes and reduce drug resistance. Methods: Following PRISMA 2020 guidelines, this systematic review focused exclusively on full-text articles published in English between 2014 and 2024. Result: The study conducted a comprehensive review of over 600 publications sourced from reputable databases, including ScienceDirect, SagePub, and PubMed. Following an initial screening, eight publications were identified as warranting more in-depth analysis. Consequently, a thorough review of these selected studies was performed to ensure a detailed and rigorous evaluation. Conclusion: Metformin, an oral antidiabetic (OAD) agent, is associated with reduced incidence and mortality from active tuberculosis in patients with diabetes. In contrast, saxagliptin, another oral antidiabetic drug, is linked to an increased risk of active tuberculosis. The continuing examination of the association between metformin and tuberculosis risk highlights the need for further research to better elucidate and validate these associations.

Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice.

Imeglimin is a recently approved oral antidiabetic agent that improves insulin resistance, and promotes insulin secretion from pancreatic β-cells. Here, we investigated the effects of imeglimin on glucagon secretion from pancreatic α-cells. Experiments were carried out in high-fat, high-sucrose diet-fed mice. The effects of imeglimin were examined using insulin and glucose tolerance tests, glucose clamp studies, and measurements of glucagon secretion from isolated islets. Glucagon was measured using both the standard and the sequential protocol of Mercodia sandwich enzyme-linked immunosorbent assay; the latter eliminates cross-reactivities with other proglucagon-derived peptides. Plasma glucagon, insulin and glucagon-like peptide-1 levels were increased by imeglimin administration in high-fat, high-sucrose diet-fed mice. Glucose clamp experiments showed that the glucagon increase was not caused by reduced blood glucose levels. After both single and long-term administration of imeglimin, glucagon secretions were significantly enhanced during glucose tolerance tests. Milder enhancement was observed when using the sequential protocol. Long-term administration of imeglimin did not alter α-cell mass. Intraperitoneal imeglimin administration did not affect glucagon secretion, despite significantly decreased blood glucose levels. Imeglimin did not enhance glucagon secretion from isolated islets. Imeglimin administration improved fatty liver by suppressing de novo lipogenesis through decreasing sterol regulatory element binding protein-1c and carbohydrate response element binding protein and their target genes, while enhancing fatty acid oxidation through increasing carnitine palmitoyltransferase I. Overall, the present results showed that imeglimin enhances glucagon secretion through an indirect mechanism. Our findings also showed that glucagon secretion promoted by imeglimin could contribute to improvement of fatty liver through suppressing de novo lipogenesis and enhancing fatty acid oxidation.

Adverse Effects of Gliptins in Type 2 Diabetics in Morocco.

Gliptins are a relatively recent class of oral antidiabetic agents used in the treatment of type 2 diabetes. The aim of this study is to identify the adverse effects of gliptins in patients with type 2 diabetes, compare the tolerability of these drugs with data from the literature, and determine patients' behavior in the face of these adverse effects with a view to optimizing their management. Our study is cross-sectional, descriptive, and analytical, involving 100 patients aged over 20 years, followed at the Endocrinology Department of the Military Hospital Mohammed V. The average age of the patients was 63 years, with a sex ratio F/H of 1.13. The median age of diabetes in the patients was 13 years, with an average blood glucose level of 1.64 and an average hemoglobin A1c of 8.26. The comorbidities were 30% cardiovascular disease, 25% hypertension, and 14% dyslipidemia, and 30% of patients had no comorbidities. Forth-six percent of patients reported adverse events and 54% did not report any adverse event. Twenty-eight percent of the adverse events were gastrointestinal, 18% skin disorders, 14% urinary tract infections, 12% hypoglycemia, 12% nervous system disorders, 8% airway infections, and 8% general disorders. This study shows that gliptins remain a safe option as the side effects seem fairly well tolerated by patients. Adverse events may impact patient compliance and pose a problem of adherence to treatment. Thus, it would be advantageous to develop therapeutic education for diabetic patients to detect and manage adverse effects.

Gender Differences in the Clinical Profile of Sodium-Glucose Cotransporter-2 Inhibitor-Related Urinary Tract Infections.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a novel class of oral antidiabetic agents with proven cardiovascular and mortality benefits. By promoting glucosuria, SGLT2Is increase the risk of genital and urinary tract infections (UTIs), which remain uncomplicated in most cases. Comparative studies detailing the gender differences in the clinical profile of SGLT2I-related UTIs (SUTIs) are lacking. Hence, this study was designed to investigate the gender-related differences in the clinical profile of SUTIs. Methodology This prospective study enrolled 100 consecutive diabetes mellitus patients with UTI symptoms who were on SGLT2Is. In addition to collecting clinical details, patients were subjected to the following investigations: complete blood counts, urea, creatine, liver function, lipid components, urine analysis, urine culture, and ultrasonography. Results Females (n = 80) outnumbered males (n = 20). Although females were younger than males (53.68 ± 10.26 vs. 63.30 ± 10.75 years, p = 0.003), body mass index (29.84 ± 7.22 vs. 24.62 ± 3.10 kg/m2, p = 0.008) and waist circumference (103.01 ± 14.49 vs. 93.75 ± 4.50 cm, p = 0.109) were higher in females. About 22.5% of females had undergone hysterectomy. The mean duration of diabetes mellitus was longer in males (10.64 ± 6.74 vs. 7.78 ± 4.75 years), whereas the median duration of SGLT2I use (4 (interquartile range (IQR) = 1-12) vs. 3 (IQR = 2-4) months) and mean HbA1c levels were not different between the two groups. A greater proportion of males were complicated by retinopathy (55% vs. 15%) and proteinuria (65% vs. 17.5%), while neuropathy (85% vs. 71.25%) rates were similar. Overall, 35% of males had complicated UTIs (renal abscess, pyelonephritis, prostatic abscess) compared to only 3.75% of females (p = 0.001). Conclusions The majority of SUTIs are uncomplicated in females whereas in males one-third are complicated infections. Although females with SUTI had a higher prevalence of obesity and dyslipidemia, males had a longer duration of diabetes mellitus and higher retinopathy prevalence. Extreme caution should be exercised in patients at risk for SUTI before prescribing SGLT2I.

Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus

AimsDipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM.MethodsPubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0.ResultsEleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, − 0.70, 95% CI − 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, − 4.50 pg/mL, 95% CI − 4.68 to − 4.32, P < 0.00001) when compared to placebo, and a comparable effect was demonstrated on TNF-alpha (WMD, 0.10 pg/mL, 95% CI − 0.11 to 0.30, P = 0.35) in comparison with active agents. Estimate was stable according to the sensitivity test. Subgroup analysis revealed that heterogeneity might not correlate with baseline glycated hemoglobin (HbA1c), age or treatment duration.ConclusionsA significant effect of DPP-4i on TNF-alpha levels was present in T2DM when compared to placebo. Administration of DPP-4i produced no significant effect on TNF-alpha in comparison with active comparators. Further studies with large samples should be performed to illustrate the impact of DPP-4i on TNF-alpha levels in T2DM.Trial registration International Prospective Register for Systematic Review (PROSPERO) number: CRD42020185479

Insulin-induced Lipohypertrophy in a Patient with Type 2 Diabetes

Abstract Lipohypertrophy (LH) is a common side effect of insulin treatment in patients with diabetes, characterized by soft, benign nodules in the subcutaneous tissue. This case report describes the management of insulin-induced LH in a 66-year-old male with type 2 diabetes. The patient had been on a combination of oral antidiabetic agents (ODAs) and biphasic human insulin for 5 years, experiencing the symptoms of numbness, leg swelling, fatigue, and frequent hypoglycemic episodes. Upon examination, LH with skin pigmentation was observed at the insulin injection sites on both calves. The patient’s laboratory investigations revealed poor glycemic control with high glycated hemoglobin percentage. To address the condition, the patient was advised to change the injection site, use proper site rotation, and change the insulin needle daily. The insulin therapy was modified by switching to biphasic premixed analog insulin injected 5 min before meals using the insulin pen. In addition, ODAs were adjusted for better glycemic control. Following these interventions, the patient reported improved glucose levels and stable kidney function. This case report emphasizes the importance of early detection and appropriate management of insulin-induced LH through patient education and insulin therapy adjustments. Health-care providers should remain vigilant for LH and educate patients on proper injection practices to optimize diabetes management and prevent complications.

Vildagliptin-Associated Bullous Pemphigoid: A Case Report

Objective: Bullous pemphigoid is a rare autoimmune skin disorder characterized by blistering, urticarial lesions, which are sometimes associated with adverse drug reactions. Vildagliptin is an oral anti-diabetic agent that selectively inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme Materials and Methods: A 75-year-old female with a known case of type 2 Diabetes Mellitus, hypertension, and hypothyroidism for the last 10 years presented with pruriginous tense bullous skin lesions over her both palms and soles. There was no mucosal involvement. Further interrogation revealed that she started taking Vildagliptin 5 days ago which was prescribed due to high levels of post-prandial blood sugar level despite already intake of Glimepiride-4 mg and Metformin-3 gm. Results: Vildagliptin was immediately advised to be stopped. She was treated with antihistamines, steroids, and conservative management which led to remission of the blisters Conclusion: Vildagliptin is the probable causative drug for developing bullous pemphigoid skin lesion which shows temporal association in this case as other concomitant drugs has no direct correlation. Therefore physicians must be aware of this rare life-threatening side effect of this medicine and advice patients to visit the hospital even the slightest cutaneous manifestation. Bullous pemphigoid can result in fatal life-threatening conditions if not treated early.

Retrospective Observational Study on Assessing Sitagliptin and Dapagliflozin as a Fixed-Dose Combination in the Indian Population With Type 2 Diabetes Mellitus: The SIDAXA Study.

Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the cardiovascular advantages ofsodium-glucose transport protein 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors in T2DM. This investigation delves into the synergistic effects of the fixed-dose combination (FDC) of sitagliptin and dapagliflozin, offering insights into its safety and efficacy for the Indian population. Methods This real-world, retrospective, observational study spanned 328 cases across 111 Indian centres, evaluating the safety, efficacy, and clinical utilization of the sitagliptin and dapagliflozin FDC in T2DM patients after obtaining ethical approval. Assessments at baseline, week four, and week 12 encompassed hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PPBG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight change. The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 29.0.1.0(171) (IBM Corp., Armonk, NY, USA) with a significance level p<0.05. Results Study participants [mean age: 51.14±5.55 years, 77.74% (n=255) males, 22.26% (n=73) females] exhibited prevalent risk factors like sedentary lifestyle (n=167, 50.91%) and smoking (n=147, 44.82%). Comorbidities included hypertension (n=235, 71.65%) and dyslipidaemia (n=139, 42.38%). Metformin (n=282, 85.98%) and sulfonylurea (n=134, 40.85%) were commonly prescribed concomitant oral antidiabetic agents (OADs). FDC administration significantly reduced HbA1c by 1.05 ± 0.83% (p < 0.0001) at week 12. FPG and PPBG showed significant reductions of 22.98 ± 22.23 mg/dL (p < 0.0001), 165.50 ± 37.02 mg/dL and 40.94 ± 36.04 mg/dL (p < 0.0001) at four weeks respectively. By week 12, significant reductions were noted in SBP (14.61±13.98mmHg reduction, p-value <0.0001), DBP (7.80±8.45mmHg reduction, p-value <0.0001), and LDL-C levels (18.14±23.95 mg/dL reduction, p-value <0.0001). In patients with established cardiovascular disease, there was reduction in HbA1c levels by 1.02 ± 0.63% after 12 weeks, with FPG decreasing by 54.52 ± 32.67 mg/dL and PPBG decreasing by 88.73 ± 44.90 mg/dL. Treatment-emergent adverse events included headache, changes in micturition, genital mycotic infection, and nausea and diarrhoea which were mild, transient, and necessitated no treatment discontinuation. Conclusion The FDC of sitagliptin and dapagliflozin significantly improved glycaemic control and lipid profiles in T2DM patients, particularly those with coronary artery disease. It demonstrated a favourable safety profile in the Indian population, signifying its potential as an effective and well-tolerated therapeutic option in patients with established cardiovascular disease.

Comprehension of Long-Term Medications in Patient with Type 2 Diabetes Mellitus: A Kap Study

OBJECTIVES The study aimed to assess the comprehension of long-term medications in patients with Type 2 diabetes mellitus. METHODOLOGY A descriptive cross-sectional study was conducted in Khyber Teaching Hospital Peshawar, Pakistan, a region with potentially low literacy rates that could affect health outcomes. After acquiring approval from the Institutional Ethical Review Board, the study utilized an appropriately designed and validated questionnaire to collect data from 305 willing participants. The questionnaire assessed demographic information, comorbid conditions, and comprehension of long-term medications. RESULTSThe mean age of the patients was 58.52 ± 10.3 years, with a mean HbA1c of 9.15 ± 2.1%. Regarding T2DM treatment, 55.1% used oral anti-diabetic agents, 34.4% used insulin, and 10.2% used both. The complications were diabetic retinopathy (40.7%), chronic kidney disease (28.9%), diabetic foot ulcers (24.9%), cerebrovascular disease (16.7%), and cardiovascular disease (16.6%). Over 50% had T2DM for more than five years. Regarding affordability and access to healthcare, 8.2% couldn't afford medications, 44.9% occasionally missed medicines due to cost, and 74.4% had easy access to healthcare. Comorbidities included hypertension (47.5%) and dyslipidemia (12.8%). CONCLUSION Medication comprehension is crucial for T2DM patients’ health outcomes. Tailored interventions can improve glycemic control and reduce complications risk.

Case Series on Implementation of Continuous Glucose Monitoring for Better Glycemic Control without Long-acting Insulin

In our case series, we are describing 6 patients with uncontrolled, complicated type 2 Diabetes Mellitus (Type 2-DM). Although they were self-monitoring their blood glucose (SMBG) at least 4 times a day, they continued to have suboptimal glucose control. Continuous glucose monitoring (CGM) was started at our Internal medicine residency primary care clinic. The patients were educated on diet, lifestyle changes, and how to adjust their insulin regimen according to their blood glucose results from the CGM as the standard of care. They were called every two weeks by the representative of our CGM team to monitor and answer any queries regarding insulin adjustment, blood glucose monitoring, diet, physical activity, or lifestyle. The CGM team included Internal medicine and transitional year medical residents and a board-certified endocrinologist who was a member of our clinic. Moreover, the patients were seen at the clinic once every month by a member of the CGM team. Long and rapid-acting Insulins were started to achieve optimal glucose control initially. Eventually, Insulin dosage was gradually reduced, and the patients we described were started on alternate agents like oral antidiabetic agents with or without injectable glucagon-like peptide GLP-1 receptor agonists. The five-hour postprandial C-peptide was checked after discontinuation of insulin in all of our patients and was normal. Within a few months of CGM initiation, there was a significant improvement in the patients’ glucose control which was maintained after stopping the Insulin. Some patients were also able to lose weight. We concluded that CGM could be initiated safely in an internal medicine residency clinic not only at specialized endocrine clinics in a project that was managed primarily by internal medicine and transitional year residents under the supervision of a member of the clinic who was board certified in endocrinologists. We also demonstrated the introduction of CGM instead of SMBG in patients with Type 2-DM helped them to achieve better glycemic control with insulin, overcome glucose toxicity, and eventually stop the insulin and maintain excellent glucose control only with oral antidiabetic agents with or without injectable GLP 1 receptor agonist.

Toxicometabolomics-based cardiotoxicity evaluation of Thiazolidinedione exposure in human-derived cardiomyocytes

IntroductionThiazolidinediones (TZDs), represented by pioglitazone and rosiglitazone, are a class of cost-effective oral antidiabetic agents posing a marginal hypoglycaemia risk. Nevertheless, observations of heart failure have hindered the clinical use of both therapies.ObjectiveSince the mechanism of TZD-induced heart failure remains largely uncharacterised, this study aimed to explore the as-yet-unidentified mechanisms underpinning TZD cardiotoxicity using a toxicometabolomics approach.MethodsThe present investigation included an untargeted liquid chromatography–mass spectrometry-based toxicometabolomics pipeline, followed by multivariate statistics and pathway analyses to elucidate the mechanism(s)of TZD-induced cardiotoxicity using AC16 human cardiomyocytes as a model, and to identify the prognostic features associated with such effects.ResultsAcute administration of either TZD agent resulted in a significant modulation in carnitine content, reflecting potential disruption of the mitochondrial carnitine shuttle. Furthermore, perturbations were noted in purine metabolism and amino acid fingerprints, strongly conveying aberrations in cardiac energetics associated with TZD usage. Analysis of our findings also highlighted alterations in polyamine (spermine and spermidine) and amino acid (L-tyrosine and valine) metabolism, known modulators of cardiac hypertrophy, suggesting a potential link to TZD cardiotoxicity that necessitates further research. In addition, this comprehensive study identified two groupings – (i) valine and creatine, and (ii) L-tryptophan and L-methionine – that were significantly enriched in the above-mentioned mechanisms, emerging as potential fingerprint biomarkers for pioglitazone and rosiglitazone cardiotoxicity, respectively.ConclusionThese findings demonstrate the utility of toxicometabolomics in elaborating on mechanisms of drug toxicity and identifying potential biomarkers, thus encouraging its application in the toxicological sciences. (245 words)

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.