Antihyperglycemic Research Articles

Using Pharmacoepidemiology to Examine the Interplay of Sulfonylureas and Infection Risk in Patients With Diabetes Mellitus.

Sulfonylureas (SU) are commonly prescribed as oral hypoglycemic agents for the management of diabetes mellitus (DM). We postulated that SU possess antimicrobial properties due to their structural resemblance to the antimicrobial agent sulfamethoxazole. Using data from Taiwan's National Health Insurance Research Database, we enrolled patients diagnosed with DM between 2000 and 2013 and followed them for a three-year period. Patients who consistently used SU were categorized into the SU cohort, while those who had never used SU formed the non-sulfonylurea (non-SU) cohort. The primary study endpoints were diagnoses of pneumonia and urinary tract infections (UTIs). Within the database, we identified a total of 15,458,554 patients with DM, with 754,601 (4.88%) in the SU cohort and 2,244,436 (14.52%) in the non-SU cohort. After individual matching based on age, gender, index day, and propensity score of comorbidities, we included 663,056 patients in each cohort. The cumulative incidence of pneumonia and UTI was 29,239 (4.41%) and 60,733 (9.16%) in the SU cohort, respectively, and 24,599 (3.71%) and 56,554 (8.53%) in the non-SU cohort, respectively. Our findings indicated that the use of SU increased the risk of pneumonia (1.26-1.60 times) and UTI (1.13-1.22 times), while also potentially offsetting the protective effects of metformin. This pharmacoepidemiological study represents a concerted effort to assess latent drug properties that may have a significant impact on the clinical management of patients with DM.

Prevalence of cardiometabolic co-morbidities in patients with vs persons without chronic hepatitis B: The FitLiver cohort study.

Chronic hepatitis B (CHB) affects > 300 million people worldwide. The combination of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality. However, international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities. In studies investigating cardiometabolic co-morbidity in patients with CHB, inconsistent findings have been observed, and both lower and higher prevalence of cardiometabolic co-morbidities compared to the general population have been reported. It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities. To investigate the prevalence of cardiometabolic comorbidities in patients with CHB and matched non-CHB comparison group. We examined patients with CHB and age-, sex-, body mass index (BMI)-, and country-of-birth matched comparison group. Defining cardiometabolic co-morbidity: Obesity (BMI > 25 kg/m2/abnormal waist-to-hip ratio), metabolic dysfunction-associated steatotic liver disease (MASLD), hypercholesterolemia (total-cholesterol > 5 mmol/L/statin use), hypertension (systolic ≥ 135 mmHg/ diastolic ≥ 85 mmHg/antihypertensive medication) and type 2 diabetes (T2D) (2-hour oral glucose tolerance test glucose > 11.1 mmol/L/HbA1c > 48 mmol/mol/ antidiabetic medication). Physical activity was evaluated using maximal oxygen consumption (VO2max), activity monitors, and a questionnaire. We included 98 patients with CHB and 49 persons in the comparison group. The two groups were well-matched, showing no significant differences in age, sex, BMI, country-of-birth, education, or employment. Among patients with CHB, the following prevalence of cardiometabolic co-morbidity was found: 77% were obese, 45% had MASLD, 38% had hypercholesterolemia, 26% had hypertension, and 7% had T2D, which did not differ significantly from the comparison group, apart from lower prevalence of hemoglobin A1c (HbA1c) ≥ 48 mmol/L or known T2D. Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group, and the patients with CHB had a shorter self-assessed sitting time. The patients with CHB and the comparison group were well-matched and had a similar prevalence of cardiometabolic comorbidities. Furthermore, both groups had low levels of physical fitness.

P-28 A CASE OF MODY TYPE 9 WITH C.89T>C MUTATION IN PAX4 GENE

Abstract Introduction Maturity-onset diabetes (MODY) is a rare type of diabetes mellitus (DM) with autosomal dominant inheritance that occurs at a young age, constituting 1-2% of all DM cases. Most MODY cases are misdiagnosed as type 1 or type 2 DM. MODY9 is a rare type caused by a mutation in the Paired box gene 4 (PAX4). We aimed to present a case that had been followed for eight years, initially diagnosed as type 1 DM, but later diagnosed with MODY type 9 after a PAX4 gene mutation was detected as a result of genetic analysis. Clinical Case A 23-year-old male patient had been followed up for eight years with a diagnosis of type 1 DM. In the evaluation, his body mass index was normal, fasting glucose level was 143 mg/dl, HbA1c was 9.5%, C peptide level was 607 pmol/L (370-1470 pmol/L), low-density lipoprotein was 112 mg/dl, and triglyceride was 60 mg/dl. He did not show signs of diabetic neuropathy or retinopathy and had no history of hospitalization due to diabetic ketoacidosis. His father also had DM. Because the patient was diagnosed at a young age, type 1 DM was accepted without checking insulin autoantibodies at the time of diagnosis, and intensive insulin therapy was started. Due to the patient's age, normal body mass index, normal C peptide level, family history and genetic evaluation was requested for monogenic diabetes diseases. As a result of the analysis performed in the patient's genetic laboratory, the C.89T>C missense variant in the PAX4 gene was detected. As a result of clinical findings and gene analysis, the patient was diagnosed with MODY type 9. Conclusion PAX4-MODY typically presents between ages 6 to 44 and is more common in men. The severity of diabetes may vary, with some patients experiencing diabetic ketoacidosis (DKA), impaired glucose tolerance, and potential complications such as renal or retinal issues, or end-stage renal failure. Treatment for MODY9 primarily involves a diabetic diet, physical activity, insulin therapy, and possibly oral hypoglycemic agents, tailored to the individual's disease progression.

Trailblazer Tepezza for thyroid

Dear Editor, Teprotumumab is a human monoclonal antibody that blocks the insulin-like growth factor-1 receptor (IGF- 1R). Approved by the Food and Drug Administration (FDA) on January 21st, 2020, under the brand name Tepezza, to be used as the treatment for Graves eye disease in adults based on its landmark success in the randomised double-blind clinical trials named OPTIC study. [1] A meta-analysis published in the International Journal of Clinical Practice in 2023 stated that at week 24 of treatment, Teprotumumab had been shown to significantly improve proptosis in 71.86% participants, diplopia in 73.65% of participants and decrease tissue inflammation, as measured by the clinical activity score to zero or one, thus improving the overall quality of life. [2] Even though the drug has adverse effects namely alopecia, fatigue and headache, the risk of these occurring was the same as the placebo group. Other potential side effects included nausea, dry skin and muscle spasms which were deemed mild.[3] One manageable side effect reported was hypoglycaemia, especially in individuals already diagnosed with diabetes, which could be corrected by adjusting their anti-diabetic medication. Importantly, this drug should be avoided in pregnancy due to its prospective teratogenic effects [2]. The promising statistics outweigh the risks associated with the drug and make teprotumumab a game-changer for thyroid eye disease patients. Pakistan has a 2% prevalence of hyperthyroidism, with a major (90%) contribution from Graves’ disease. [4] Although this 2% seems insignificant, yet it amounts up to 4.2 million people. Unfortunately, this drug has not reached Pakistan yet and we still resort to using conventional treatments namely lubricants and steroids despite their worrying side effects and contraindications in patients having other comorbid conditions which majority of the people of Pakistan suffer from such as diabetes, hypertension, osteoporosis and hepatic dysfunction. [5] The government should subsidize the use of this novel drug in TED patients by incentivizing its availability and training physicians to monitor the patients taking the infusions. The patients will need to be educated about the adverse profile and danger signs when to report their symptoms to the doctor. Teprotumumab is not just a treatment, it is a cure for most patients. Should we not switch from using the current harmful conventional drugs to the more contemporary ones with better outcomes?

Clinical and biochemical factors associated with amygdalar metabolic activity

We investigated clinical factors and biochemical markers associated with amygdalar metabolic activity evaluated by [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) in 346 subjects without a history of malignant neoplasms. Univariate regression analysis revealed significant relationships between amygdalar metabolic activity and fasting plasma glucose (FPG), glycated hemoglobin, coronary artery disease (CAD) history, aspirin use, oral hypoglycemic agents (OHAs) use, and asymmetric dimethylarginine (ADMA). In multiple stepwise regression analysis, FPG and CAD history were independently associated with amygdalar metabolic activity. Moreover, in 36 patients with type 2 diabetes mellitus (T2DM), additional OHAs treatment significantly improved glycemic and metabolic parameters, and decreased ADMA concentrations. Baseline and Δpigment epithelium-derived factor (PEDF), a marker of insulin resistance, was a significant associate with Δamygdalar metabolic activity. Our study demonstrates that FPG and CAD history were independently associated with amygdalar metabolic activity in subjects without a history of malignant neoplasms. In T2DM patients, PEDF might regulate amygdala metabolic activity.

The impact of diabetes and antidiabetics on uro-oncological disease outcomes: A single center experience.

To determine the impact of diabetes and antidiabetic medications on referral and pathological outcomes in uro-oncology cases. We report preliminary results from a single center study. We retrospectively collected data from 781 patients treated between 2018 and 2023 for radical prostatectomy (RP) for prostate cancer (PCa), radical cystectomy (RC) for bladder cancer (BCa), radical nephroureterectomy (RNU) for upper tract urothelial carcinoma, partial nephrectomy (PN) and radical nephrectomy (RN) for renal cell cancer (RCC). A total of 617 (79%) patients were non-diabetics and 164 (21%) were diabetics. Patient data were assessed for differences between diabetics and non-diabetics. All diabetic patients had a significantly higher BMI than non-diabetic patients (p<0.05 for PCa and p=0.006 for RC respectively). In diabetic patients with PCa, a lower proportion of ISUP grade 3 and 5 PCa was seen (p=0.047). In diabetic RCC patients on anti-diabetic medication, there was a significantly higher incidence of recurrence rates after RN (p=0.015). Penile cancer was diagnosed in diabetic patients at an older age (p=0.019). Significantly, higher BMI was observed for RP and RC in diabetic patients, as well as for RCC after RN. Diabetics showed a significantly higher occurrence of recurrence for RCC after RN.

Pharmacist-led deprescribing of cardiovascular and diabetes medication within a clinical medication review: the LeMON study (Less Medicines in Older Patients in the Netherlands), a cluster randomized controlled trial.

Deprescribing inappropriate cardiovascular and antidiabetic medication has been shown to be feasible and safe. Healthcare providers often perceive the deprescribing of cardiovascular and antidiabetic medication as a challenge and therefore it is still not widely implemented in daily practice. The aim was to assess whether training focused on conducting a deprescribing-oriented clinical medication review (CMR) results in a reduction of the inappropriate use of cardiovascular and antidiabetic medicines. A cluster randomized controlled trial involving 20 community pharmacists, who conducted a clinical medication review in 10 patients. The intervention group received training on deprescribing. Patients 70years or older with polypharmacy having a systolic blood pressure below 140mmHg and using antihypertensive medication and/or an HbA1c level below 54mmol/mol and using antidiabetic medication, were included. Follow-up took place within 4 weeks (T1) and after 3 months (T2). The primary outcome measure was the proportion of patients with one or more cardiovascular and antidiabetic medicine deprescribed within 3 months after the CMR (T2). A total of 71 patients in the intervention group and 69 patients in the control group were included. At T2, 32% of patients in the intervention group and 26% in the control group (OR 1.4, CI 0.65-2.82, p = 0.413) had one or more cardiovascular or antidiabetic medicines discontinued. Regarding any medication, these percentages were 51% and 36%, (OR 1.8, CI 0.92-3.56, p = 0.085) respectively. Increased awareness and ability of community pharmacists to deprescribe medication and use of general practitioners' data, led community pharmacists and general practitioners to successfully conduct a more deprescribing-focused CMR in daily practice. Further research is needed to assess the necessity of additional training to optimize the deprescribing of cardiovascular and antidiabetic medication. The study was registered at The Netherlands Trial Register (registration no: NL8082).

Recent advances in pancreatic α-cell transdifferentiation for diabetes therapy

As the global prevalence of diabetes mellitus rises, traditional treatments like insulin therapy and oral hypoglycemic agents often fail to achieve optimal glycemic control, leading to severe complications. Recent research has focused on replenishing pancreatic β-cells through the transdifferentiation of α-cells, offering a promising therapeutic avenue. This review explores the molecular mechanisms underlying α-cell to β-cell transdifferentiation, emphasizing key transcription factors such as Dnmt1, Arx, Pdx1, MafA, and Nkx6.1. The potential clinical applications, especially in type 1 and type 2 diabetes characterized by significant β-cell dysfunction, are addressed. Challenges, including low transdifferentiation efficiency, cell stability, and safety concerns, are also included. Future research directions include optimizing molecular pathways, enhancing transdifferentiation efficiency, and ensuring the long-term stability of β-cell identity. Overall, the ability to convert α-cells into β-cells represents a transformative strategy for diabetes treatment, offering hope for more effective and sustainable therapies for patients with severe β-cell loss.

An update on ocular effects of anti-diabetic medications.

The global increase in the prevalence of type 2 diabetes has led to the development and implementation of new classes of anti-diabetic medications, introducing advanced therapeutic options for the management of the disease. These new medications, though primarily designed to regulate blood glucose levels, also have applications in weight management, potentially transforming the current approaches to diabetes treatment. Newer medications, however, have ophthalmic side effects with controversies in trials and real-life data. We conducted a comprehensive assessment of the ocular benefits and adverse effects of both traditional and newer-generation anti-diabetic drugs. Our primary focus is on how these newer medications affect the stage of diabetic retinopathy. Additionally, we explore the associations between these medications and other ocular conditions, including age-related macular degeneration, glaucoma, orbital conditions, and diseases impacting the ocular surface. Furthermore, we provide contextual background by discussing the ocular effects of traditional anti-diabetic drugs.

Prospective role of lupeol from Pterocarpus santalinus leaf against diabetes: An in vitro, in silico, and in vivo investigation.

Diabetes mellitus (DM) can be treated with various medications. However, individuals in underdeveloped countries may face challenges in using these treatments due to side effects and high costs. Anti-diabetic medications can inhibit enzymes, such as α-amylase, which is responsible for breaking down carbohydrates. In this investigation, 16 phytoconstituents were identified from Pterocarpus santalinus leaf extract through GC-MS analysis, and their significant antioxidant activities were noted. Among these, the pure compound lupeol demonstrated α-amylase inhibition activity of 86.13±1.27% (IC50=58.50±0.83μg/mL) in vitro. Additionally, lupeol showed the highest binding affinity in silico using PyRx and CB-Dock, with values of -9.5 and -9.3kcal/mol, respectively. The in silico analysis also indicated that lupeol possesses acceptable ADMET properties, suggesting its potential as an anti-diabetic drug. A molecular dynamics simulation lasting 500 ns was conducted to evaluate hydrogen bonds, RMSF, RMSD, Rg, and SASA, confirming the stability and integrity of the docking scenarios. In STZ-induced diabetic mice, lupeol significantly reduced blood glucose levels by 70.82% from day 0 to day 28. Furthermore, lupeol markedly decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while improving high-density lipoprotein cholesterol (HDL-C) levels in these mice. The antidiabetic effect of lupeol was further validated through histological examinations of the pancreas, heart, kidney, and liver of treated mice, alongside correlation analysis, CAP, and ANOSIM tests. Based on the findings from the in vitro, in silico, and in vivo investigations, this study concludes that lupeol may have potential anti-diabetic effects through the inhibition of the α-amylase enzyme.

Tacrolimus and diabetic rodent models.

Tacrolimus (TAC) is an immunosuppressant widely utilized in organ transplantation. One of its primary adverse effects is glucose metabolism disorder, which significantly increases the risk of diabetes. Investigating the molecular mechanisms underlying TAC-induced diabetes is essential for developing effective prevention and treatment strategies for these adverse effects. In addition, TAC can induce cost-effective, non-obese animal models of diabetes, where the metabolic parameter changes closely resemble those observed during the onset and progression of type 2 diabetes (T2DM), post-transplantation diabetes mellitus (PTDM), and associated complications. This review, based on articles indexed in PubMed up to August 19, 2024, identified 48 studies focusing on TAC-induced diabetic rodent models and 22 studies exploring the effects of TAC on diabetic or obese rodent models. These studies were systematically summarized based on TAC dosage, route of administration, duration of administration, and glucose metabolism indices used for evaluation. Additionally, the impact of TAC dose reduction or discontinuation on glucose metabolism was assessed, along with pharmacological agents that modulate TAC-induced diabetes, including anti-diabetic medications, anti-inflammatory and antioxidant compounds, biologics, and antibiotics. Key signaling pathways implicated in TAC-induced diabetes include CaN/NFAT, PI3K/AKT/mTOR, and TGF-β/Smad, all of which impair islet β-cell function, thereby contributing to diabetes development. This review provides a concise summary of the characteristics of relevant murine models, offering valuable guidance for selecting appropriate and economical animal models for future research.

Critical Appraisal of Pharmaceutical Therapy in Diabetic Cardiomyopathy-Challenges and Prospectives.

Diabetes mellitus (DM) is a multifaceted disorder with a pandemic spread and a remarkable burden of cardiovascular mortality and morbidity. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development of cardiac dysfunction, which is accompanied by heart failure (HF) symptoms in the absence of obvious reasons like ischemic heart disease, hypertension, or valvulopathies. Several pathophysiological mechanisms have been proposed, including metabolic disorders (e.g., glycation products), oxidative stress, low-grade inflammation, mitochondrial dysfunction, etc., which should guide the development of new therapeutic strategies. Up to now, HF treatment has not differed between patients with and without diabetes, which limits the expected benefits despite the high cardiovascular risk in the former group. However, DBCM patients may require different management, which prioritize anti-diabetic medications or testing other novel therapies. This review aims to appraise the challenges and prospectives of the individualized pharmaceutical therapy for DBCM.

Comparing demographic/clinical characteristics, health care resource utilization, and costs among patients with type 2 diabetes and established atherosclerotic cardiovascular disease with and without the use of cardioprotective medications.

Type 2 diabetes (T2D) causes increased health care resource utilization (HCRU) and costs in the United States. People with T2D are more likely to have atherosclerotic cardiovascular disease (ASCVD), which is associated with significant morbidity and mortality. Medical associations recommend cardioprotective antidiabetic medications, including sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs), to reduce the risk of cardiovascular events in patients with T2D with established, or a high risk of, ASCVD, but not all eligible patients receive these medications. To describe demographic/clinical characteristics and antidiabetic medication prescription patterns and compare HCRU and costs among patients with T2D and ASCVD with or without SGLT2i and/or GLP-1 RA use. We conducted a retrospective cohort study using the Merative MarketScan database of longitudinal US health care claims data with patients enrolled from July 1, 2014, to December 31, 2022. Patients with T2D and ASCVD receiving SGLT2is and/or GLP-1 RAs (case cohort) were compared with patients with T2D and ASCVD not receiving SGLT2is and/or GLP-1 RAs (control cohort) during a 12-month baseline period pre-index and a 12-month follow-up period post-index. The index date was SGLT2i/GLP-1 RA prescription for the case cohort and random health care visit for the control cohort. Baseline patient characteristics are reported before propensity score matching (PSM); HCRU and medical costs are reported after PSM. Before PSM, each cohort included 3,386 patients; after PSM, each cohort included 2,351 patients. Patients in the case cohort were significantly more likely to experience myocardial infarction (case, 26.2%; control, 21.5%; P < 0.001) or peripheral artery disease (case, 28.6%; control, 26.1%; P < 0.024) during the baseline period. Patients in the case cohort had significantly lower baseline Charlson Comorbidity Index scores than patients in the control cohort (case, 1.8; control, 2.1; P < 0.001). Patients in the case cohort had significantly fewer all-cause inpatient visits per patient (case, 0.4; control, 0.6; P < 0.001) and all-cause emergency department visits per patient (case, 0.9; control, 1.0; P = 0.024). Patients in the case cohort had significantly lower all-cause inpatient costs (case, $13,977; control, $22,056; P < 0.001), other all-cause outpatient costs (case, $16,504; control, $24,739; P < 0.001), and all-cause total medical costs including pharmacy costs (case, $51,143; control, $58,648; P = 0.01) in the 12-month follow-up period. Patients with T2D and ASCVD receiving SGLT2is and/or GLP-1 RAs within 12 months of ASCVD diagnosis may benefit from lower HCRU and costs.

Real-World Treatment Patterns Among US Patients With Type 2 Diabetes Mellitus Initiating Treatment With Once Weekly Semaglutide for Diabetes.

Injectable once weekly semaglutide for diabetes (OW sema) is a medication approved in 2017 for the treatment of patients with type 2 diabetes (T2DM). In clinical trials, OW sema has been shown to be effective at helping patients achieve glycemic targets. However, more data are needed to understand how patients who initiate treatment with OW sema are treated in the real world and to aid prescribers in making treatment decisions. This study characterized noninsulin antidiabetic medication use patterns among US patients with T2DM initiating treatment with OW sema. In this retrospective, claims-based study, patients (15,588) were included if they had at least 1 claim for OW sema between January 1, 2018 and December 31, 2019, were at least 18 years old, were continuously enrolled in the health plan, and had at least 1 claim indicating a diagnosis of T2DM. All patients had at least 1 line of therapy (LOT) that started on the date of the first fill for OW sema. Data related to pre-index date demographics and clinical characteristics were collected, as were data on patient regimens and LOTs. The length of the LOT was calculated, and the top 10 noninsulin treatment regimens were reported in each LOT. In the first LOT, OW sema monotherapy was the most common regimen. More than one third (36.5%) of patients had 1 LOT until the end of follow-up and most patients who had a second (52.1%) or third (72.0%) LOT continued it to the end of the study. Among the top 10 regimens, 42.2% of patients with a second LOT and 45.8% of patients with a third LOT had an LOT that included OW sema. This study describes medication regimens within the first year of OW sema use. Among patients initiating OW sema, monotherapy was the most common regimen. These results provide insight into real-world usage patterns of this medication.

The prevalence and risk factors among people with diabetes mellitus in a selected rural community of kerala

The recent statistics of India in 2023 suggest a prevalence of 10.1 crores of diabetes in the community, with three in four adults with diabetes living in low- and middle-income countries, and half of them are unaware of their condition. This study aims to assess the prevalence of diabetes mellitus among people in a selected rural community and to identify the risk factors among people with diabetes mellitus.A quantitative research approach with a descriptive, cross-sectional study design was adopted. The participants were 824 adults, males, and females, aged above 21 years, and selected using a convenience sampling method. Data was collected from two selected wards of Athirampuzha panchayat, Kottayam, Kerala. Data were collected from a larger survey conducted in this area. The tool used was a structured questionnaire with three parts: a socio-demographic tool, lifestyle-related factors, and a specific part for collecting diabetes-related information. The results indicated that nearly 15.90% of the population had diabetes mellitus (n=131), and majority were above above 50 years. A majority of the diabetes-affected people were females (n 69, 52.67%), married (n= 104, 79.39%), unemployed (n =76, 58.02%), homemakers (n=72, 54.96%), and belonged to nuclear families (n=81, 61.83%). Most of them have been diagnosed with diabetes mellitus for the past 5-10 years and are on treatment with oral hypoglycemic agents (n=107, 81.68%). About 32% of them had familial risk factors (n=42). Among the comorbid conditions, 41.98% (n= 55) had hypertension. A majority of the participants were having a BMI above normal (51.15%, n-= 67, BMI=25.0 -29.9) and were following sedentary lifestyle habits (n=113, 86.26%). : The study highlight the importance of targeting the lifestyle risk factors for preventing diabetes mellitus in the community at an early stage.

Sodium-Glucose Cotransporter 2 Inhibitors and Changes in Epicardial Adipose Tissue: A Systematic Literature Review And Meta-Analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk. This systematic review and meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on EAT. We performed a literature search for studies assessing the changes in epicardial adipose tissue volume/thickness before and after treatment with an SGLT2 inhibitor. We excluded reviews, editorials, case reports/case series, experimental studies, and studies that did not use SGLT2 inhibitors as the intervention. The main outcome of interest was the change in EAT volume/thickness at follow-up. The literature search yielded 72 results. After the application of the exclusion criteria, a total of 11 studies were selected for data extraction and inclusion in the meta-analysis. A mean of 6.57ml decreased EAT volume, and EAT thickness was reduced by a mean of 1.55mm. We detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness compared to the control group (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial betweenstudy heterogeneity (I2: 94%, p<0.001). Results remained robust even after the exclusion of any single study. Subgroup analysis revealed a significantly greater effect size in randomized studies. Funnel plot inspection and Egger's regression test did not indicate the presence of publication bias Conclusion: This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure outcomes.

Effects of antidiabetic agents on lipid metabolism of skeletal muscle: A narrative review.

Metabolic syndrome-related diseases frequently involve disturbances in skeletal muscle lipid metabolism. The accumulation of lipid metabolites, lipid-induced mitochondrial stress in skeletal muscle cells, as well as the inflammation of adjacent adipose tissue, are associated with the development of insulin resistance and metabolic dysfunction. Consequently, when antidiabetic medications are used to treat various chronic conditions related to hyperglycaemia, the impact on skeletal muscle lipid metabolism should not be overlooked. However, current research has predominantly focused on muscle mass rather than skeletal muscle lipid metabolism and its interplay with glucose metabolism. In this review, we summarised the latest research on the effects of antidiabetic drugs and certain natural compounds with antidiabetic activity on skeletal muscle lipid metabolism, focusing on data from preclinical to clinical studies. Given the widespread use of antidiabetic drugs, a better understanding of their effects on skeletal muscle lipid metabolism merits further attention in future research.

Exploring the Therapeutic Efficacy of Ethanolic Extract of Benincasa hispida in Alloxan Induced Diabetic Rats

Since the dawn of civilization, humans have used herbal medicine to treat medical ailments. This study seeks to evaluate the efficacy of Benincasa hispida as an anti-diabetic agent and its impact on lipid profiles. We assessed the efficacy of the anti-diabetes medication using the alloxan-induced diabetic model. Only the 900 mg/kg dosage exhibited statistically significant antidiabetic effects (p &lt; 0.05) when compared to the 300 and 600 mg/kg dosages. Notwithstanding a slight reduction in these parameters, no groups demonstrated statistically significant results regarding HDL, LDL, and total cholesterol. The triglyceride value of 97.70 ± 7.50* yielded statistically significant results (p &lt; 0.05). Conversely, SGPT and SGOT exhibited no statistically significant effects at dosages of 300, 600, or 900 mg/kg. Group 5 exhibited statistically significant results (p &lt; 0.05) in the kidney function test in case of urea, with a value of 93.24 ± 9.23* after the administration of an extract at a dose of 600 mg/kg. No statistically significant results were seen in any groups concerning creatinine levels.

Safety and efficacy of dapagliflozin versus empagliflozin as add-on therapy in type 2 diabetes mellitus management

Objectives: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are drugs used as the oral hypoglycaemic that have a significant effect in lowering blood glucose, glycated haemoglobin (HbA1c), weight and blood pressure in patients of type 2 diabetes mellitus (T2DM). SGLT-2 inhibitors, such as empagliflozin and dapagliflozin, are used in addition to diet and exercise to help persons with T2DM improve their glucose control. The drugs are combined with other antidiabetic medications or used as monotherapy. Materials and Methods: The aim of this study was to evaluate the efficacy and the safety of the drug dapagliflozin against empagliflozin in individuals with T2DM as an add-on treatment. The study is carried out in a Tertiary Care Hospital in Coimbatore using a prospective observational research design. T2DM patients with a HbA1c level of &gt;7% are included in the study. Patient information was collected by patient interviews and from the patient file. Participants in the study are categorised into two groups: one group consists of patients taking oral dapagliflozin in doses of 5 mg or 10 mg alongside other oral hypoglycemic agents (OHAs), while the other group comprises patients taking oral empagliflozin in doses of 10 mg or 20 mg alongside other OHAs. The endpoints were to assess the safety and effectiveness of each SGLT-2 inhibitor by monitoring changes in the diabetic profile, body weight, body mass index (BMI), blood pressure and cardiovascular risk. Results: The study included 100 patients, with 56 males and 44 females. Most participants were aged 51–60 years. In both treatment groups, A and B, significant reductions in body weight Group A: 3.14 kg and Group B: 2.29 kg and BMI Group A: 0.65 kg/m2 and Group B: 0.84 kg/m2 were observed after 6 months of treatment follow-up. Both groups experienced decreases in HbA1c levels from baseline to 6 months of treatment. The mean differences in HbA1c were 0.36% in Group A and 0.55% in Group B; empagliflozin led to a more significant reduction in HbA1c (0.19%) compared to dapagliflozin. Significant reductions were noted in fasting blood sugar (FBS) and postprandial blood sugar (PPBS) levels in both groups. Both dapagliflozin and empagliflozin were associated with reductions in systolic blood pressure (SBP) after 6 months of therapy. Dapagliflozin showed a greater reduction in SBP of 10.26 mmHg compared to 4.2 mmHg with empagliflozin. In addition, dapagliflozin increases diastolic blood pressure (DBP) by 2.25 mmHg, while empagliflozin reduces DBP by 3.61 mmHg. While both groups experienced reductions in SBP, only the group using empagliflozin showed a significant reduction in DBP. The Framingham risk score showed significant reductions in mean differences observed in both groups after 6 months of treatment, with a mean difference of 1.08% in Group A and 2.17% in Group B. However, the score is not statistically different between the groups. Both drugs exhibited equal effects on the prevention of cardiovascular risk. Both drugs exhibited a similar safety profile, with mild-to-moderate adverse events reported, including urinary tract infections (Group A: 18% and Group B: 12%) and hypoglycaemia (Group A: 24% and Group B: 20%) during the study period. Conclusion: SGLT-2 inhibitors dapagliflozin and empagliflozin have favourable efficacy and safety in the management of T2DM; both drugs show equal effects on HbA1c, FBS, PPBS, body weight and BMI. Empagliflozin led to a more significant reduction in HbA1c compared to dapagliflozin. In both hypertensive and non-hypertensive patients, dapagliflozin exhibited greater systolic blood pressure reduction compared to empagliflozin, whereas empagliflozin exhibited greater reduction in diastolic blood pressure compared to dapagliflozin; in contrast, dapagliflozin has shown to increase DBP. Further investigation is required to explore the blood pressure effects of SGLT-2 inhibitors in a large population. In addition, these drugs decreased cardiovascular risk. Both medications exhibited fewer instances of hypoglycaemic episodes and urinary tract infections.

Influence of Ageing on the Pharmacodynamics and Pharmacokinetics of Chronically Administered Medicines in Geriatric Patients: A Review.

As people age, the efficiency of various regulatory processes that ensure proper communication between cells and organs tends to decline. This deterioration can lead to difficulties in maintaining homeostasis during physiological stress. This includes but is not limited to cognitive impairments, functional difficulties, and issues related to caregivers which contribute significantly to medication errors and non-adherence. These factors can lead to higher morbidity, extended hospital stays, reduced quality of life, and even mortality. The decrease in homeostatic capacity varies among individuals, contributing to the greater variability observed in geriatric populations. Significant pharmacokinetic and pharmacodynamic alterations accompany ageing. Pharmacokinetic changes include decreased renal and hepatic clearance and an increased volume of distribution for lipid-soluble drugs, which prolong their elimination half-life. Pharmacodynamic changes typically involve increased sensitivity to various drug classes, such as anticoagulants, antidiabetic and psychotropic medications. This review examines the primary age-related physiological changes in geriatrics and their impact on the pharmacokinetics and pharmacodynamics of medications.