Metformin Group Research Articles

Effects of Letrozole And Metformin Versus Metformin alone on incretin in Iraqi patients with PCOS

I Background: The emergence of numerous novel therapeutic agents for managing T2DM has expanded the assortment of tailored therapies available for PCOS sick. One illustration of these is the incretin-based therapeutic agents. Patients and methods:The extanttrainingcomprised 75 sickthrough an age extent of 18 to less than 40 years. Patients were categorized into three groups: metformin group (positive control group) and they received metformin as 500 mg per-oral (bid); letrozole group who were treated using 2.5 mg per-oral (bid), and combination groups who received both agents with similar doses as above. Each group included 25 females. Informationalmost age and body mass index (BMI) stayed included in the study. Serum measurement of incretin (GLP-1) was done before treatment and 90 days after treatment using Enzyme-Linked Immunosorbent Assay. Results: There stayed no importantvariance in mean age (p = 0.981) betweentraining groups and means of age were 29.24 ± 6.10 years, 29.56 ± 5.50 years and 29.44± 5.83 years, respectively and the range of age was between 18 and 40 years. In addition, in this training, there stayed no importantalteration in mean BMI (p = 0.534) among study groups and means of BMI were 28.80 ±2.72 kg/m2, 27.53 ±1.95 kg/m2 and 27.07 ±1.99 kg/m2, respectively and the range of BMI was between 21.07 and 31.18 kg/m2. Serum incretin (GLP-1) level showed no significant variation among study groups, the mean levels were in the range of 10.87 -13.79 ng/ml and the range of values was from 9.56 -14.49 ng/ml. Changes in BMI are shown in. Metformin alone caused in more important weight decrease; nevertheless, adding of letrozole caused significant reduction in body mass index, letrozole alone also affect body weight significantly. It was observed that combined use of either drug resulted in more significant change of GLP-1 level at (p ≤ 0.001). Conclusion: Combined treatment with letrozole and metformin is safe and efficient in femalesby PCOS resultant in weight decrease, improved insulin

White Tea Consumption Alleviates Anthropometric and Metabolic Parameters in Obese Patients

Background and Objectives: Obesity and related disorders are an increasing global health problem. Achieving and maintaining long-term weight loss through lifestyle changes and/or pharmacological interventions have not met expectations. Dietary supplements and alternative treatments have also shown limited effectiveness in this regard. The consumption of green tea in general has been shown to benefit obese patients, with effects attributed to caffeine, catechins, polyphenols and other components. However, the potential of white tea to prevent and treat the negative effects of obesity has not been addressed so far. In this study, the effect of white tea (WT) consumption in obese individuals was anthropometrically and biochemically investigated. Materials and Methods: Based on anthropometric and biochemical assessments, the patients were assigned to the control, orlistat, metformin and WT groups. Patients were given a diet and exercise program and one of either orlistat, metformin or WT for 12 weeks. At the end of the 12th week, the anthropometric and biochemical measurements were reassessed. Results: Body weight, waist circumference and BMI parameters decreased significantly in all groups. TNF-α, IL-6, IL-1β and MMP-9 levels decreased significantly in the WT group. In addition, contrary to a significant elevation in HDL-C, the serum cholesterol, LDL-C and TG levels decreased significantly. Furthermore, leptin, ghrelin and asprosin levels decreased significantly. Serum glucose levels decreased significantly in all groups except for the control. In the WT group, while there was a significant decrease in the levels of serum PL MDA and 8-OHdG, the opposite was true for GSH. Conclusions: The oral consumption of WT, its availability and its potency in obesity treatment and prevention pave the way for further delineation of the mechanisms of actions of its bioactive compounds at the cellular and endocrinological levels.

Metformin Treatment Is Not Associated with Altered PD-L1 Expression in Diabetic Patients with Oral Squamous Cell Carcinoma.

Background: The anti-neoplastic activity of metformin is a subject of current debate. Preclinical data have suggested that metformin enhances PD-L1 anti-tumor effects in various cancer entities by decreasing insulin levels and inducing energetic stress. However, its impact on PD-L1 expression remains unclear in a clinical setting. Therefore, we aim to investigate the impact of metformin treatment in type 2 diabetes mellitus (DM) patients on PD-L1 expression in patients with oral squamous cell carcinoma (OSCC). Methods: We performed a retrospective analysis of patients with DM and OSCC treated at our tertiary referral center over a period of 12 years. The tumor proportion score (TPS), immune cell score (IC), and combined positive score (CPS) were used to quantify PD-L1 expression. PD-L1 expression of patients receiving metformin was compared to a control group without metformin prescription. Results: A total of 68 patients diagnosed with OSCC and DM were analyzed, with 24 receiving and 44 not receiving metformin therapy. No statistically significant differences were identified between the metformin and non-metformin groups for any of the scores (TPS: p = 0.818; IC: p = 0.748; CPS: p = 0.387). Conclusions: In contrast to previous studies, we could not find significant differences in PD-L1 expression between patients with and without metformin intake. Further research needs to shed light on the exact mechanism of metformin in different tumor entities. A comprehensive understanding of metformin's role in cancer therapy could provide valuable insights for potential use of metformin as an adjuvant treatment to immune checkpoint therapy.

Efficacy of drugs treatment in patients with endometrial hyperplasia with or without atypia: A systematic review and network meta-analysis.

Endometrial hyperplasia (EH) is a hyperplastic endometrial lesion with irregular gland size, increased glands, and increased glandular interstitial ratio. During follow-up, some EH progressed further to endometrial cancer. It is crucial to provide timely treatment for EH and improve the overall prognosis of EH patients. We searched the PubMed, ClinicalTrials.gov., and Embase databases for studies published from their inception to March 31, 2023. The methodological quality of each study was evaluated in accordance with the Cochrane Collaboration's tool for assessing the risk of bias. The RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis statistical analysis; and the relative risk and 95% confidence interval along with the mean difference and 95% confidence interval, were used as evaluation indexes. We included 21 randomized controlled trials involving a total of 2276 women with EH, 6 studies were of high quality, and 15 were of moderate quality. The blinding of subjects and intervention providers was identified as the main source of potential bias. Six interventions were addressed in the network meta-analysis: medroxyprogesterone acetate (MPA), plus metformin, norethisterone (NET), levonorgestrel-releasing intrauterine system (LNG-IUD), megestrol acetate, and other drugs. In the direct meta-analysis, we found the probability of endometrial complete regression (CR) in the LNG-IUD group to be significantly higher than those in the NET. In the network meta-analysis, we found the probability of CR in the NET group to be significantly lower than those in the MPA and plus metformin groups, the probability of CR in the LNG-IUD group to be significantly higher than those in the NET, the probability of CR in the other drugs group to be significantly higher than those in the LNG-IUD. The NET group had the lowest incidences of endometrial complete regression, plus metformin could have a better outcome. According to the 21 randomized controlled trials included in this study, MPA is the most effective for EH endometrial outcome when applied as a single agent, while the combination of metformin can achieve a more significant effect.

Maternal metformin administration during the pre-gestation period improves transient cerebral ischemia injury in male offspring rats

Purpose: It seems that maternal intervention, which may involve epigenetic mechanisms, can affect cerebral ischemia in offspring. Metformin consumption by the mother activates the AMP-activated protein kinase (AMPK) pathway. Metformin has also induced the AMPK and protected neurons in cerebral ischemia. This study investigates the effect of maternal metformin administration, which activates the AMPK pathway, on cerebral ischemia in offspring Methods: Animals were separated into four groups: sham, 2-vessels occlusion (2VO), Met+2VO, Met+compound c (CC)+2VO. Female rats were administrated with metformin at a dose of 200 mg.kg-1 body weight for 2 weeks prior to mating. After the final metformin injection, each female rat was paired with an intact adult male to allow for mating. Sixty-days old offspring underwent cerebral ischemia and then memory-related tests were done. Results: Current data revealed that the neurological deficits score was reduced Met+2VO group (P<0.001), and the memory increased (P<0.001) in comparison to the 2VO. The Bcl-2/Bax ratio declined in the metformin group (P<0.001) while the Brain-Derived Neurotropic Factor (BDNF), c-fos, p-AMPK/AMPK ratio and Histone H3K9 acetylation in the hippocampus augmented significantly compared to the 2VO group (P<0.001). Conclusion: These findings indicated that the metformin intervention via AMPK activation could improve the movement disability, enhance spatial memory, increase neural plasticity, and augment the bioenergetics state and histone acetylation in the hippocampus of the offspring.

Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3β/Snail Signaling Axis.

Chronic inflammation in the salivary glands (SG) often triggers epithelial-mesenchymal transition (EMT), leading to the loss of acinar function and promoting fibrosis. This study explores the role of Metformin in mitigating partial EMT in SG inflammation. In vitro, human salivary gland epithelial cells (hSGECs) were treated with lipopolysaccharide (LPS) and Metformin. EMT markers and the PI3K/Akt/GSK3β/Snail signaling axis were assessed using RNA-seq and Western blot analysis. In vivo, a Wharton's duct ligation rat model was employed to mimic chronic sialadenitis (CS). Nine Wistar rats were randomly divided into three groups: Control, Ligation and Ligation + Metformin groups, with three rats per group. After ductal ligation, the Ligation + Metformin group received 100mg/kg of Metformin via intragastric administration, while the Control and Ligation groups received an equivalent saline every 24h. Histological analysis, immunohistochemical and immunofluorescence staining were conducted to evaluate acinar morphology, EMT, and the PI3K/Akt/GSK3β/Snail signaling axis. The results showed that in CS tissues, atrophied acinar cells underwent partial EMT. In vitro, Metformin reversed LPS-induced EMT in hSGECs. RNA-seq and Western blot revealed that Metformin achieved this effect by targeting the PI3K/Akt/GSK3β/Snail signaling axis (P < 0.01). In ductal ligation models, Metformin treatment restored ligation-induced acinar damage and functional loss (P < 0.01). Further histological evidence supported that Metformin mitigated EMT by inhibiting inflammatory activation of PI3K/Akt/GSK3β/Snail signaling axis (P < 0.01). In conclusion, Metformin alleviates partial EMT in SG inflammation by targeting the PI3K/Akt/GSK3β/Snail signaling axis, highlighting its potential as a therapeutic strategy for SG inflammation.

Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats

BackgroundRecent studies have highlighted type 2 diabetes (T2DM) as a significant risk factor for the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This investigation aimed to assess electroacupuncture’s (EA) impact on liver morphology and function in T2DM rats, furnishing experimental substantiation for its potential to stall MAFLD progression in T2DM.MethodsT2DM rats were induced by a high-fat diet and a single intraperitoneal injection of streptozotocin, and then randomly assigned to five groups: the T2DM group, the electroacupuncture group, the metformin group, combination group of electroacupuncture and metformin, combination group of electroacupuncture and Compound C. The control group received a standard diet alongside intraperitoneal citric acid - sodium citrate solution injections. After a 6-week intervention, the effects of each group on fasting blood glucose, lipids, liver function, morphology, lipid droplet infiltration, and fibrosis were evaluated. Techniques including Western blotting, qPCR, immunohistochemistry, and immunofluorescence were employed to gauge the expression of key molecules in AMPK-associated glycolipid metabolism, insulin signaling, autophagy, and fibrosis pathways. Additionally, transmission electron microscopy facilitated the observation of liver autophagy, lipid droplets, and fibrosis.ResultsOur studies indicated that hyperglycemia, hyperlipidemia and IR promoted lipid accumulation, pathological and functional damage, and resulting in hepatic steatosis and fibrosis. Meanwhile, EA enhanced the activation of AMPK, which in turn improved glycolipid metabolism and autophagy through promoting the expression of PPARα/CPT1A and AMPK/mTOR pathway, inhibiting the expression of SREBP1c, PGC-1α/PCK2 and TGFβ1/Smad2/3 signaling pathway, ultimately exerting its effect on ameliorating hepatic steatosis and fibrosis in T2DM rats. The above effects of EA were consistent with metformin. The combination of EA and metformin had significant advantages in increasing hepatic AMPK expression, improving liver morphology, lipid droplet infiltration, fibrosis, and reducing serum ALT levels. In addition, the ameliorating effects of EA on the progression of MAFLD in T2DM rats were partly disrupted by Compound C, an inhibitor of AMPK.ConclusionsEA upregulated hepatic AMPK expression, curtailing gluconeogenesis and lipogenesis while boosting fatty acid oxidation and autophagy levels. Consequently, it mitigated blood glucose, lipids, and insulin resistance in T2DM rats, thus impeding liver steatosis and fibrosis progression and retarding MAFLD advancement.

An antifibrotic compound that ameliorates hyperglycaemia and fat accumulation in cell and HFD mouse models.

Appropriate management of blood glucose levels and the prevention of complications are important in the treatment of diabetes. We have previously reported on a compound named HPH-15 that is not only antifibrotic but also AMP-activated protein kinase (AMPK)-activating. In this study, we evaluated whether HPH-15 is useful as a therapeutic medication for diabetes. We examined the effects of HPH-15 on AMPK activation, glucose uptake, fat accumulation and lactic acid production in L6-GLUT4, HepG2 and 3T3-L1 cells, as a model of muscle, liver and fat tissue, respectively. Additionally, we investigated the glucose-lowering, fat-accumulation-suppressing, antifibrotic and AMPK-activating effect of HPH-15 in mice fed a high-fat diet (HFD). HPH-15 at a concentration of 10 µmol/l increased AMPK activation, glucose uptake and membrane translocation of GLUT4 in each cell model to the same extent as metformin at 2 mmol/l. The production of lactic acid (which causes lactic acidosis) in HPH-15-treated cells was equal to or less than that observed in metformin-treated cells. In HFD-fed mice, HPH-15 lowered blood glucose from 11.1±0.3 mmol/l to 8.2±0.4 mmol/l (10 mg/kg) and 7.9±0.4 mmol/l (100 mg/kg) and improved insulin resistance. The HPH-15 (10 mg/kg) group showed the same level of AMPK activation as the metformin (300 mg/kg) group in all organs. The HPH-15-treated HFD-fed mice also showed suppression of fat accumulation and fibrosis in the liver and fat tissue; these effects were more significant than those obtained with metformin. Mice treated with high doses of HPH-15 also exhibited a 44% reduction in subcutaneous fat. HPH-15 activated AMPK at lower concentrations than metformin in vitro and in vivo and improved blood glucose levels and insulin resistance in vivo. In addition, HPH-15 was more effective than metformin at ameliorating fatty liver and adipocyte hypertrophy in HFD-fed mice. HPH-15 could be effective in preventing fatty liver, a common complication in diabetic individuals. Additionally, in contrast to metformin, high doses of HPH-15 reduced subcutaneous fat in HFD-fed mice. Presumably, HPH-15 has a stronger inhibitory effect on fat accumulation and fibrosis than metformin, accounting for the reduction of subcutaneous fat. Therefore, HPH-15 is potentially a glucose-lowering medication that can lower blood glucose, inhibit fat accumulation and ameliorate liver fibrosis.

Empagliflozin add‐on therapy is superior to metformin monotherapy in diabetic patients with NAFLD: An open‐label, single‐center, pilot clinical trial

AbstractBackgroundThe prevalence of non‐alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, inflammation, and advanced fibrosis, is high among type‐2 diabetes mellitus (T2DM) patients. Empagliflozin (EMPA), a sodium‐glucose cotransporter‐2 inhibitor, has been well established to improve glycemic status in T2DM. However, evidence of the desirable effects of EMPA, when added to the standard treatment in diabetics with coexisting NAFLD, has yet to be determined.ObjectiveThe main objective of the current study is to explore the benefits of EMPA on hepatic fat content in patients with T2DM and NAFLD, who received metformin (MET) monotherapy.MethodsIn this open‐label clinical trial study, 60 patients with T2DM and NAFLD were assigned to either the MET + EMPA or MET group in an up‐titrated manner for 24 weeks. Anthropometric characteristics, blood glucose indices, lipid profile, liver enzymes, and steatosis grades were measured at baseline and 24 weeks after the intervention.ResultsThe results showed that in patients with a mean age of 53.26 ± 7.64 who received MET+ EMPA, all the parameters had a greater decrease than the MET group. In addition, the reduction of FBS, BS, HbA1C, TG, and ALT had a statistically significant difference between the two groups after 24 weeks follow‐up (p &lt; 0.05). Notably, in the MET+ EMPA group, there was a substantial improvement in steatosis grades based on the fibroscan and ultrasound modality results.ConclusionThe EMPA add‐on therapeutic schedule in uncontrolled T2DM patients with NAFLD significantly ameliorated steatosis stages, liver function, anthropometric features, and biochemical parameters.

Neonatal Outcomes in Patients with Gestational Diabetes Mellitus Treated with Metformin: A Retrospective Study in Saudi Arabia.

Gestational diabetes mellitus (GDM) is a common endocrine disease that can occur during pregnancy, increasing the risk of fetal morbidity and mortality. Metformin is a commonly used therapeutic approach for managing GDM. However, there is controversy regarding the effects of metformin on fetal outcomes during pregnancy. This study aimed to evaluate the safety of metformin in relation to neonatal complications, compared to treatment with insulin and/or specialized diets. This was a retrospective study that included pregnant women who were diagnosed with GDM and treated with specialized diets, metformin, or insulin. Data were collected from patients' electronic medical records and analyzed to evaluate the risk of neonatal outcomes in the metformin group compared to the others. The study included 234 women with GDM. There was no difference between the metformin and insulin groups in terms of the rates of neonatal outcomes, while neonatal hypoglycemia, neonatal hyperbilirubinemia, large for gestational age, and respiratory distress were higher in the metformin group when compared to the diet group. Metformin slightly increased the risk of a lower APGAR score compared to diet alone. Metformin was found to be a safe therapy for the fetus when used to manage GDM, compared to insulin therapy. More randomized studies are needed to confirm these findings in the Saudi population.

Metformin and small for gestational age babies: findings of a randomised placebo-controlled clinical trial of metformin in gestational diabetes (EMERGE).

Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes because of suboptimal glucose management and glucose control and excessive weight gain. Metformin can offset these factors but is associated with small for gestational age (SGA) infants. We sought to identify risk factors for SGA infants, including the effect of metformin exposure on SGA status. In this prespecified secondary analysis of the EMERGE trial, which evaluated the effectiveness of metformin vs placebo in treating GDM and found reduced gestational weight gain and longer time to insulin initiation with metformin use, we included women with a live-born infant and known infant birthweight and gestational age at delivery. We compared the numbers of SGA infants in both groups and explored baseline predictive factors to help identify those at highest risk of delivering an SGA infant. Baseline maternal characteristics were similar between SGA and non-SGA pregnancies. On multivariable-adjusted regression, no baseline maternal variables were associated with SGA status. Mothers of SGA infants were more likely to develop pre-eclampsia or gestational hypertension (18.2% vs 2.0%, p=0.001; 22.7% vs 5.4%, p=0.005, respectively); after multivariable adjustment, pre-eclampsia was positively associated with SGA status). Among SGA pregnancies, important perinatal outcomes including preterm birth, Caesarean delivery and neonatal care unit admission did not differ between the metformin and placebo groups (20.0% vs 14.3%, p=1.00; 50.0% vs 28.6%, p=0.25; 13.3% vs 42.9%, p=0.27, respectively). Pre-eclampsia was strongly associated with SGA infants. Metformin-exposed SGA infants did not display a more severe SGA phenotype than infants treated with placebo. Clinical Trials.gov NCT02980276; EudraCT number: 2016-001644-19.

Impact of metformin, statin, aspirin and insulin on the prognosis of uHCC patients receiving first line Lenvatinib or Atezolizumab plus Bevacizumab

Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1–3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1–3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0–2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1–2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.

Hepatoprotective Role of Aqueous Extract of Kasni Seeds in Alloxan-Induced Diabetic Mice

Background: Diabetes mellitus (DM) is a prevalent metabolic disorder characterized by chronic hyperglycemia, leading to various systemic complications, including liver damage. Traditional antidiabetic drugs are often associated with adverse effects, prompting interest in safer, natural alternatives like Kasni (Cichorium intybus) seeds, known for their hepatoprotective properties.Objective: This study aimed to evaluate the hepatoprotective effects of Kasni seed aqueous extract in alloxan-induced diabetic mice.Methods: Thirty-two male albino mice were divided into three groups: control, metformin-treated, and Kasni-treated. Diabetes was induced using alloxan monohydrate (150 mg/kg). The Kasni-treated group received 400 mg/kg of Kasni extract orally for 28 days. Blood glucose levels were monitored, and liver tissues were analyzed histologically to assess hepatocyte arrangement, central vein morphology, sinusoidal inflammation, and fatty globule presence.Results: The Kasni-treated group showed a significant reduction in blood glucose levels (140.2 ± 8.7 mg/dL) compared to the metformin group (180.4 ± 10.5 mg/dL) (p &lt; 0.05). Histological analysis revealed restored hepatocyte arrangement, reduced fatty globules, and normalized central vein morphology in the Kasni-treated group.Conclusion: Kasni seed aqueous extract exhibits significant hepatoprotective effects in alloxan-induced diabetic mice, suggesting its potential as a natural therapeutic agent for managing liver complications in diabetes.

The effects of spirulina (Arthrospira platensis) supplementation on serum fasting blood glucose, lipid parameters, and oxidative stress markers in male rats with type 2 diabetes

Background. Some studies have shown that Spirulina has biological properties exerting beneficial effects on human health. This study aimed to evaluate the effects of Spirulina supplementation on serum glucose, lipid parameters, and oxidative stress markers in male rats with streptozotocin/nicotinamide–induced T2DM. Methods. In this experimental study, rats with diabetes were divided into six groups: healthy control, diabetic control, diabetic-metformin, diabetic-Spirulina 100 mg/dL, diabetic-Spirulina 200 mg/dL, and healthy control-Spirulina 200 mg/d. At the end of the study (28 days), the blood samples were collected, and the fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined. Results. Significant reductions (P&lt;0.001) were found in serum level of FBG in Metformin and Spirulina 100 mg/kg compared with diabetic control group. The groups were different regarding the serum levels of HDL-C post-intervention. ANOVA analysis also showed significant differences between the Spirulina 100 mg/kg or Metformin group and diabetic control group regarding the serum level of MDA (P&lt;0.05). Conclusion. Spirulina at a dose of 100 mg/kg may have contributed to controlling the fasting blood glucose and oxidative stress. Practical Implications. Our study results suggested that Spirulina, as a promising agent, at lower doses may have been considered as a functional food for the management of diabetes mellitus.

Role of oral hypoglycaemic drugs in preventing complication in non-alcoholic fatty liver disease with type 2 diabetes mellitus.

To determine the prevalence of non-alcoholic fatty liver disease, and the effect of oral hypoglycaemic drugs and lifestyle modifications in reducing fatty liver changes and liver enzymes in these patients. The comparative, observational study was conducted at the Department of Pharmacology, Sohail University, Karachi, from October 2022 to October 2023, and comprised patients of either gender having elevated liver enzymes and ultrasound finding of fatty liver changes along with raised glycated haemoglobin, transaminases, total cholesterol and triglycerides. The participants were prescribed oral hypoglycaemic agents by endocrinologists. Those given empaglifazolin + metformin were in group A, empaglifazolin + linglaptin in group B, sitaglaptin + metformin in group C, metformin alone in group D and sitaglaptin alone in group E. Lifestyle modifications were advised in all the treatment groups, while control group F was only advised lifestyle modifications. The intervention lasted 3 months. Investigations included B-mode ultrasound liver, liver enzymes and glycated haemoglobin, which were done at baseline and after the intervention. Data was analysed using SPSS 25. Of 200 patients, 40 were males and 160 were females in ratio of 1:4. The overall mean age was 48±16 years. There were 154(77%) patients who had non-alcoholic fatty liver disease with type 2 diabetes mellitus, while 46(23%) had only fatty liver changes. There were 50(25%) patients in group A, 30(15%) in group B, 30(15%) in group C, 40(20%) in group D, 10(5%) in group E and 40(20%) in group F. Post-intervention improvement was noted in 48(24%) patients, with 20(41.7%) of them being in group A. The prevalence of non-alcoholic fatty liver disease with type 2 diabetes was high. Combination of empagliflozin + metformin along with lifestyle modifications was highly effective in reducing fatty changes and the level of liver enzymes.

Effect of Metformin on Peripheral Nerve Morphology in Type 2 Diabetes: A Cross-Sectional Observational Study.

Diabetic peripheral neuropathy (DPN) affects around 50% of the 500 million people with type 2 diabetes worldwide and is considered disabling and irreversible. The present study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes. 69 type 2 diabetes participants receiving metformin were recruited and underwent clinical assessment, peripheral nerve ultrasound, nerve conduction studies and axonal excitability studies. 318 participants who were not on metformin were also concurrently screened, and 69 were selected as disease controls and matched to the metformin participants for age, sex, diabetes duration, BMI, HbA1c and use of other diabetes therapies. Medical record data over the previous 20 years were analysed for previous metformin use. Mean tibial nerve cross-sectional area (CSA) was lower in the metformin group (metformin 14.1 ∓ 0.7 mm2, non-metformin 16.2 ∓ 0.9mm2, p=0.038), accompanied by reduction in neuropathy symptom severity (p=0.021). Axonal excitability studies demonstrated superior axonal function in the metformin group and mathematical modelling demonstrated that these improvements were mediated by changes in nodal Na+ and K+ conductances. Metformin treatment is associated with superior nerve structure, clinical and neurophysiological measures. Treatment with metformin may be neuroprotective in DPN.

Neonatal outcomes of gestational diabetes mellitus (GDM) mothers: A cross-sectional study comparing medical nutritional therapy, metformin, and insulin treatments at a tertiary care centre

Gestational Diabetes Mellitus (GDM) poses a rising global health challenge, affecting 10-14.3% of pregnant women. This study aimed to investigate and compare neonatal outcomes among mothers with GDM treated with Medical Nutritional Therapy (MNT), metformin, and insulin at a tertiary care center. Understanding the impact of these treatments on neonatal outcomes is crucial for optimal care.Conducted at a tertiary care center in Chennai, India, this cross-sectional study included 160 GDM mothers identified through medical records from December 2021 to December 2023. Inclusion criteria covered women aged 18 and above, experiencing singleton pregnancies, diagnosed with GDM, and maintaining regular follow-up. Data analysis included birth weight, Apgar scores, neonatal hypoglycemia, and preterm birth rates. Multinomial logistic regression determined adjusted odds ratios.The study analyzed the distribution of perinatal factors among 160 neonates, revealing that 41.3% were delivered vaginally, while 58.8% were through cesarean section. The majority were preterm, with 118 being appropriate for gestational age.Neonatal Intensive Care Unit (ICU) admission was noted in 34.4% of cases, while 62.7% did not. Neonatal hypoglycemia was observed in 36.3% of cases, and seizures were present in 19.4%. Apgar scores were low in 23.8% of cases.A multinomial logistic analysis found that the Metformin, Insulin, and Metformin + Insulin groups had significantly higher odds of having a Cesarean section compared to the diet-only group. However, the Metformin group had lower odds of preterm birth, NICU admission, neonatal hypoglycemia, seizures, and AGA. The Metformin group had higher odds of LGA and Apgar score &amp;#60;7 at both the 1st and 5th minutes. No significant differences were found in the odds of preterm birth, NICU admission, or seizures between the diet-only and Metformin groups.This pioneering South Indian study of 160 neonates born to GDM mothers compared different treatment options. Metformin, alone or with insulin, showed comparable neonatal outcomes to insulin. Caution in GDM deliveries is recommended for optimal well-being. The study emphasizes the need for further research considering maternal outcomes as potential confounders to comprehensively understand GDM treatments and neonatal outcomes.

Metformin treatment improves depressive symptoms associated with type 2 diabetes: A 24-week longitudinal study

ObjectiveMetformin is a medication that is widely used for lowering blood sugar in patients with type 2 diabetes. Metformin was shown to have significant antidepressant effects; however, it is not clear whether metformin treatment improves outcomes in patients with type 2 diabetes who have concomitant depressive symptoms. MethodsA total of 475 patients with type 2 diabetes mellitus with depressive symptoms were included in this study and divided into metformin and nonmetformin groups according to whether they were taking metformin. The DASS-21 was used to assess patients' depression and anxiety scores before and after a 24-week intervention. In addition, general information about whether the patients had developed complications from diabetes and whether they had been diagnosed with other diseases was assessed. Results(1) After 24 weeks, anxiety and depression scores were significantly lower in the metformin group than in the nonmetformin group. (2) The prevalence of depressive symptoms was significantly greater in female type 2 diabetic patients than in male patients (OR = 2.039, 95 % CI = 1.160–3.568). (3) People with type 2 diabetes who develop complications from diabetes (OR = 1.794, 95 % CI = 1.015–3.171) and those diagnosed with other conditions are more likely to experience depressive symptoms. ConclusionMetformin has an ameliorative effect on type 2 diabetes. However, women, those with diabetes complications, and those with type 2 diabetes who are also diagnosed with other conditions are more likely to experience depressive symptoms.

Metformin versus Metformin Plus Statin Effect on Lipid Profile in Type 2 Diabetic Patients

Metformin is commonly used drug for type 2 diabetes and may also impact lipid profiles. Statins are often combined with metformin to manage dyslipidemia, but their comparative efficacy on lipid profiles is not well established. This study aimed to compares the effects of metformin alone versus metformin with statins on lipid profiles and to investigate the impact of different metformin doses on these profiles. A cross-sectional study was conducted at Aljabal Alakdar Diabetic Clinic in East Libya from July to December 2023, involving 200 adults with type 2 diabetes. Participants were divided into Group A (metformin only) and Group B (metformin plus statin). Inclusion criteria were adults aged 18-75 years, on metformin for at least 3 months, with recent lipid profile data, and who provided informed consent. Exclusion criteria were additional lipid-lowering drugs or any medications known to affect lipid profiles, type 1 diabetes, severe comorbidities, and pregnancy. Data were analyzed using SPSS version 27 with MANOVA, and significance was set at p &lt; 0.005. The mean age was 58.62 years, mean diabetes duration was 11.43 years, with 47.5% males and 52.5% females. Mean HbA1c was 7.98%, mean urea was 36.5 mg/dL, and mean creatinine was 0.95 mg/dL. Lipid profile parameters included mean LDL cholesterol at 89.09 mg/dL, HDL cholesterol at 47.71 mg/dL, total cholesterol at 175.6 mg/dL, and triglycerides at 169.4 mg/dL. The key lipid parameters showed a significant difference (p &lt; 0.000) between groups, with the metformin-only group exhibiting lower LDL, HDL, triglycerides, and total cholesterol compared to the metformin plus statin group. Our study found that metformin alone achieved better lipid control than metformin combined with statins, with a 1g dose showing notable antihyperlipidemic effects.

β-cell function and long-term glycemic control in patients newly diagnosed with type 2 diabetes with moderate hyperglycemia after a 6-month course of basal insulin therapy

AimsTo evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia. MethodsPatients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the β-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months. ResultsWe randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was − 2.06 ± 1.37 %, −0.43 ± 0.32 %, and − 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy. ConclusionA 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion.