Combination Of Metformin Research Articles

Lactobacillus rhamnosus GG Combined with Metformin Alleviates Alcohol-Induced Liver Inflammation in Mice by Maintaining the Intestinal Barrier and Regulating Treg/Th1 Cells.

Disturbances of the intestinal barrier enabling bacterial translocation exacerbate alcoholic liver disease (ALD). Lactobacillus rhamnosus GG (LGG) has been shown to exert beneficial effects in gut dysbiosis and chronic liver disease. The current study assessed the combined effects of LGG and metformin, which play roles in anti-inflammatory and immunoregulatory processes, in alcohol-induced liver disease mice. A diet comprising 5% alcohol for 4 weeks was employed to develop an alcohol-induced liver injury model. Mice were orally administered LGG, metformin, or their combination on alternate days. Tight junction (TJ) proteins, gut microbiome composition, inflammatory cytokines, Jun N-terminal kinase (JNK), and p38 signals were assessed. When compared with treatment with LGG or metformin alone, combined LGG and metformin treatment substantially lowered the symptoms of inflammation, steatosis, and elevated liver enzymes caused by alcohol administration. Combination treatment significantly improved intestinal microecology, evidenced by the recovery of intestinal flora, TJ proteins, and intestinal villi. Combination treatment reduced hepatic inflammation by blocking p38 and JNK phosphorylation. The combination of LGG and metformin corrected immune-response dysregulation and improved ALD by enhancing the intestinal microbiome, restoring mucosal barrier integrity, modulating immune function, and decreasing liver injury. These results provide information for the development of intestinal microbiota-based preventive and therapeutic agents against ALD.

Dapagliflozin combined with metformin improves blood glucose, bone metabolism and bone mineral density in elderly patients with type 2 diabetes mellitus complicated with osteoporosis.

The incidence of type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP) (T2DM-OP) is growing. Dapagliflozin and metformin are commonly prescribed to manage glycemic levels in T2DM patients. We investigated the clinical efficacy of combining dapagliflozin with metformin in elderly patients with T2DM-OP. Totally 144 T2DM-OP patients were prospectively enrolled and allocated into two groups: the Metformin and Dapagliflozin + Metformin groups. Each group received treatment for 12 months. Fasting peripheral blood samples were collected before and after 12 months of treatment. Glycemic parameters and bone metabolic parameters were measured using oral glucose tolerance test, automatic biochemical analyzers, or liquid chromatography. Bone mineral density (BMD) changes at lumbar vertebrae (L1-4), femoral neck (FN) and total hip (TH) were assessed using dual-energy X-ray bone mineral densitometry. Pain severity was evaluated using the visual analog scale (VAS). The total effective rate, fracture incidence, and adverse reaction rate were also evaluated. After 12 months, both groups showed improvements in glycemic parameters, bone metabolic parameters, and BMD at L1-4, FN, and TH, and reductions in VAS scores. The Dapagliflozin + Metformin group exhibited more significant improvements. The overall effective rate was higher and fracture incidence, was lower in Dapagliflozin + Metformin group, with comparable rates of adverse reactions and safety profiles between the two groups. Taken together, treatment with a combination of dapagliflozin and metformin led to improvements in blood glucose levels, bone metabolism, and BMD in elderly patients with T2DM-OP, demonstrating superior efficacy and safety compared to metformin monotherapy.

Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.

Metabolic alterations are commonly associated with various cancers and are recognized as contributing factors to cancer progression, invasion, and metastasis. Drug repurposing, a strategy in drug discovery, utilizes existing knowledge to recommend established drugs for new indications based on clinical data or biological evidence. This approach is considered a less risky alternative to traditional drug development. Metformin, a biguanide, is a product of Galega officinalis (French lilac) primarily prescribed for managing type 2 diabetes, is recognized for its ability to reduce hepatic glucose production and enhance insulin sensitivity, particularly in peripheral tissues such as muscle. It also improves glucose uptake and utilization while decreasing intestinal glucose absorption. Statins, first isolated from the fungus Penicillium citrinum is another class of medication mainly used to lower cholesterol levels in individuals at risk for cardiovascular diseases, work by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is essential for cholesterol biosynthesis in the liver. Metformin is frequently used in conjunction with statins to investigate their potential synergistic effects. Combination of metformin and simvastatin has gathered much attention in cancer research because of its potential advantages for cancer prevention and treatment. In this review, we analyze the effects of metformin and simvastatin, both individually and in combination, on key cancer hallmarks, and how this combination affects the expression of biomolecules and associated signaling pathways. We also summarize preclinical research, including clinical trials, on the efficacy, safety, and potential applications of repurposing metformin and simvastatin for cancer therapy.

Research Progress on the Combination of Semaglutide and Metformin in the Treatment of Obese PCOS

Research Progress on the Combination of Semaglutide and Metformin in the Treatment of Obese PCOS

Gastrointestinal symptoms in patients receiving imeglimin in combination with metformin: A post-hoc analysis of imeglimin clinical trial data.

An increased rate of gastrointestinal (GI) symptoms is reported in patients with type 2 diabetes receiving imeglimin plus metformin vs monotherapy or in combination with other antidiabetic drugs. This post-hoc analysis explored GI symptom incidence, risk factors for their occurrence, and the impact on therapeutic efficacy during imeglimin and metformin combination therapy. Data were derived from the 52-week, open-label, phase 3 TIMES-2 trial in Japanese type 2 diabetes patients. Patients in the imeglimin plus metformin group were divided into two subgroups based on the presence of GI symptoms and diarrhea, with efficacy and safety assessed. Factors associated with their occurrence were explored using multivariate logistic regression analysis. Of 64 patients analyzed, GI symptoms and diarrhea occurred in 40.6% (n = 26) and 17.2% (n = 11) of patients, respectively. Metformin dose and patient age did not significantly affect their incidence. Events occurred more frequently within the first 4 months of treatment. Approximately half resolved within 1 week, and most were mild. Type 2 diabetes duration <5 years was significantly associated with diarrhea (odds ratio = 5.979; P = 0.039). Significant hypoglycemic effects were observed from baseline, irrespective of GI symptoms or diarrhea. However, the degree of HbA1c improvement tended to be greater in patients with GI symptoms and diarrhea. Increased awareness regarding the potential for GI symptoms, including diarrhea, during imeglimin plus metformin combination therapy is warranted. This data will provide clinicians with useful information regarding symptomatic treatment when it occurs and help determine whether to continue treatment administration and is expected to improve patient adherence.

Positive impact of DPP-4 or SGLT2 inhibitors on mild cognitive impairment in type 2 diabetes patients on metformin therapy: A metabolomic mechanistic insight.

Mild cognitive impairment is increasingly recognized as a complication of type 2 diabetes (T2D). Although currently no disease-modifying treatments for cognitive disorders exist, interest surged in potential neuroprotective effects of newer anti-diabetic drugs. This study investigates the impact of newer anti-diabetic drug classes, dipeptidyl peptidase-4 (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) - on cognitive decline in T2D patients on metformin therapy. A prospective observational cohort study was conducted, with a follow-up duration of 6 months. The study compared the cognitive performance of T2D patients on metformin monotherapy to those on a combination of metformin with DPP-4i or SGLT2i, using the Montreal Cognitive Assessment Battery. A group of healthy volunteers served as a reference. At baseline, patients receiving combination therapy had a cognitive performance comparable to that of healthy volunteers, while those on metformin monotherapy scored lower. These differences persisted for patients who completed the follow-up, though there was no change within group. Baseline differences were independent of glycemic control, blood lipids, renal function, and serum inflammatory markers. Comprehensive metabolomics and lipidomics revealed that T2D patients on metformin monotherapy exhibited enriched purine, glutathione and sphingolipid metabolism, with alterations in xanthine, L-pyroglutamic acid, and several sphingomyelins. These changes suggest increased oxidative stress in T2D, mitigated in the combination therapy group, as evidenced by total serum antioxidant capacity. As such, we conclude that the combination of DPP-4i or SGLT2i with metformin positively impacts cognitive function in T2D patients by modulating metabolic pathways rather than improving glycemic control, peripheral diabetic complications, or systemic inflammation.

A prospective, multicentre study evaluating safety and efficacy of a fixed dose combination of Remogliflozin etabonate, Vildagliptin, and Metformin in Indian patients with type 2 diabetes mellitus (Triad-RMV)

AimsThe ICMR INDIAB-17 study revealed a diabetes prevalence of 11.4% in India, emphasizing the need for effective treatment for glycemic control. A Phase IV study was conducted to evaluate the safety and efficacy of a Fixed Dose Combination (FDC) of Remogliflozin, Metformin and Vildagliptin (RMV) in Type 2 Diabetes Mellitus (T2DM) patients uncontrolled on Metformin plus SGLT2 inhibitor or Metformin plus DPP4 inhibitor dual therapy.MethodsA total of 215 patients (mean age: 46.4 years; 64% male, 36% female) were enrolled across multiple centers in India. The study population included patients with a baseline HbA1c ≥ 8% at the time of screening. The primary objective was to assess safety based on treatment-emergent adverse events (TEAEs), while the secondary. aim was to evaluate effectiveness in terms of glycemic (HbA1c, fasting plasma glucose, postprandial glucose) and extra-glycemic measures (renal and lipid parameters). Statistical analysis was conducted using paired t-tests and the Wilcoxon signed-rank test for within-group comparisons, and the Bonferroni correction was applied to adjust for multiple comparisons. Effectiveness was evaluated at baseline, week 12, and week 24.ResultsThe study demonstrated statistically significant reductions in mean HbA1c levels from baseline to both week 12 and week 24 (p < 0.00001). At 24, weeks, 45.1% of patients achieved target HbA1c levels of ≤ 7%. Significant reduction was also observed in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels. Renal parameters remained stable or improved, and lipid profile parameters, including LDL-C and triglycerides, showed favorable changes. Adverse events of special interest, including hypoglycemia and urinary tract infections, were reported in 4.7% of patients, with no serious adverse event recorded.ConclusionsThe twice daily triple FDC of RMV was well tolerated, safe and effective in patients with Type 2 Diabetes Mellitus uncontrolled on dual drug therapy of Metformin plus SGLT2i or Metformin plus DPP4i. The treatment led to significant improvements in glycemic control and other metabolic parameters over 24 weeks, without compromising renal function or causing serious adverse events.Trial registrationCTRI, CTRI/2022/05/042581. Registered 17 May 2022, https//ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=68,757&EncHid=36127.16500&modid=1&compid=19.

Real-world safety of dapagliflozin plus metformin in patients of type 2 diabetes mellitus in China: Post-hoc analysis of the DONATE study.

DONATE (NCT03156985) is a large-scale real-world study investigating the safety of dapagliflozin in Chinese type 2 diabetes mellitus (T2DM) patients. This post-hoc analysis aims to further evaluate the real-world safety of dapagliflozin plus metformin. Safety outcomes were assessed in patients receiving concomitant dapagliflozin and metformin, with or without other antidiabetics. The safety of dapagliflozin-based dual-therapies and dapagliflozin and metformin-based triple-therapies were also analysed. Among the 2,990 patients in DONATE, 2,165 (72.4 %) received concomitant metformin. Among these 2,165 patients, 780 (36.0 %) experienced ≥ 1 adverse event (AE), 129 (6.0 %) experienced serious AE (SAE), and 96 (4.4 %) experienced AE leading to dapagliflozin discontinuation. The most common AEs were upper respiratory tract infection (4.0 %), urinary tract infection (UTI, 2.1 %) and constipation (1.5 %). The most common AEs of special interest of dapagliflozin were UTI (2.3 %), genital tract infection (1.5 %) and hypoglycaemia (1.1 %). In the dapagliflozin and metformin dual-therapy subgroup, the incidences of AE, SAE and AE leading to dapagliflozin discontinuation were 26.7 %, 2.5 %, and 1.9 %, respectively, numerically lower than that of the total population and most other dual-therapy subgroups. These patients also had numerically improved metabolic outcomes than baseline. Dapagliflozin and metformin combination therapy is well-tolerated in real-world Chinese T2DM patients.

Probiotics Combined with Metformin Improves Sperm Parameters in Obese Male Mice through Modulation of Intestinal Microbiota Equilibrium.

The decline in sperm parameters among obese males has attracted significant scholarly interest. The intestinal microbiota plays a crucial role in obesity, and investigating the intestinal-reproductive axis may offer a novel molecular approach to addressing the decline in male sperm parameters caused by obesity. To clarify whether probiotics, either alone or in conjunction with metformin, can enhance sperm parameters in obese male mice and assess the underlying mechanisms involved.6-week-old male mice were constructed as obese models. Probiotics and metformin were used as intervention conditions. Changes in inflammatory factors and ROS content were detected by ELISA, morphological changes in testicular and colon tissues were observed by H&E staining, changes in intestinal microbiota abundance were detected by 16SrRNA gene sequencing, and changes in metabolites such as blood glucose, blood lipids, and lipopolysaccharide were detected by biochemical testing to investigate the mechanism of probiotics, metformin, and their combination to ameliorate reproductive impairment in obese male mice. Our results revealed that high-fat diet would result in reduced testicular spermatogenic tubule hierarchy, decreased spermatogenic cell counts, decreased sperm concentration and motility, and altered abundance of intestinal microbiota, whereas the combination of probiotics and metformin could restore high-fat-mediated pathophysiological alterations thereby ameliorating spermatogenic disorders in mice.The combination of probiotics and metformin can attenuate inflammation and oxidative stress, while enhancing androgen production to improve testicular spermatogenic function by re-construction intestinal microbiota equilibrium in HFD mice.

The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease.

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) were often coexistent conditions driven by insulin resistance and systemic inflammation. Effective management strategies that address both metabolic disorders were urgently needed. This study investigates the effect of combining semaglutide, a glucagon-like peptide-1 receptor agonist, with metformin on liver inflammation and pancreatic beta-cell function in patients with T2DM and NAFLD. This retrospective study analyzed 261 patients with T2DM and NAFLD treated at our institution from January 2021 to December 2023. Patients were divided into two groups: 127 received metformin alone (M group), and 134 received a combination of semaglutide and metformin (SAM group). Liver inflammation and fibrosis were assessed using alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GTP), and the FIB-4 index. Pancreatic beta-cell function and insulin sensitivity were evaluated using the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo). Post-treatment, the SAM group showed significantly greater improvements in liver inflammation markers (ALT: 23.59±5.67U/L in SAM vs. 25.56±5.46U/L in M; AST: 18.97±3.94U/L in SAM vs. 20.15±3.95U/L in M), reduced fibrosis (FIB-4 index: 1.05±0.44 in SAM vs. 1.16±0.51 in M), and enhanced beta-cell function (Matsuda index: 5.18±1.09 in SAM vs. 4.84±1.15 in M; DIo: 0.18±0.06 in SAM vs. 0.16±0.05 in M). Glycemic control, as indicated by reduced HbA1c, was also superior in the SAM group. The combination of semaglutide and metformin significantly improves liver inflammation, fibrosis, and beta-cell function in patients with T2DM and NAFLD compared to metformin alone.

A Phase III, Double-Blind, Randomized, Multicenter, Clinical Trial to Evaluate the Efficacy and Safety of a Fixed-Dose Combination of Metformin Hydrochloride and Myo-Inositol Compared to Metformin in Patients With Polycystic Ovary Syndrome.

Background Polycystic ovary syndrome (PCOS) poses a significant health concern among reproductive-aged women and is characterized by ovarian dysfunction, hyperandrogenism, and insulin resistance. This study aims to assess the efficacy and safety of metformin and myo-inositol combination therapy compared to metformin monotherapy in patients with PCOS. Materials and methods This was a phase III, double-blind, randomized controlled clinical trial. A total of 196 patients with PCOS were randomized in a 1:1 ratio to receive either a fixed-dose combination of metformin hydrochloride 500 mg and myo-inositol 600 mg (Met-Myo) or metformin 500 mg alone (Met) twice daily for 24 weeks. The primary study endpoints were improvement in insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR) at week 24 and improvement in menstrual cycle disturbances at 12 and 24 weeks. Results The Met-Myo combination demonstrated a significantly superior response with 63 (75%) patients showing improvement in HOMA-IR compared to 54 (60.67%) in the Met group (p = 0.049) at week 24. The improvement in the number of patients with heavy menstrual blood flow (>80 mL) was significantly greater in the Met-Myo group (four patients, 4.76%) compared to the Met group (six patients, 6.74%) at week 24 (p = 0.029). Improvement in the percentage of patients with normal menstrual frequency and infrequent menstruation from baseline to week 24 was significantly greater in the Met-Myo group compared to the Met group (p = 0.049). Safety assessments revealed a low and comparable incidence of mild adverse events. Conclusion Metformin-myo-inositol combination therapy is superior to metformin monotherapy in addressing menstrual irregularities and improving insulin resistance in PCOS patients, thereby providing a promising avenue for optimizing the management of PCOS.

Study on the mechanism on Yi-guan-jian decoction alleviating cognitive dysfunction in type 2 diabetes mellitus.

Yi-guan-jian decoction (YGJ) is a traditional Chinese medicine prescription commonly used for treating syndromes associated with Yin deficiency in the liver and kidney, as well as Qi-obstructed in liver. YGJ has shown potential alleviating cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the precise mechanisms are not yet fully understood. This study aims to reveal the mechanism by which YGJ alleviates cognitive dysfunction in T2DM. Various doses of YGJ were administered to T2DM rats with cognitive dysfunction for 8 weeks. The positive control group received a combination of metformin and memantine. Cognitive function was assessed in T2DM rats using the Morris water maze test during treatment. Changes in gut microbiota and bile acids in the intestine were evaluated, and their interactions analyzed. Additionally, this study also evaluated the expressions of inflammatory markers (IL-1β,TNF-α, IL-16, IL-18 and CRP protein), Tau protein, neurotransmitter (5-HT and GABA), and bile acid receptor (FXR, PXR, VDR, and TGR5). YGJ significantly alleviated insulin resistance and hyperlipidemia, reduce the levels of inflammatory factors in serum and hippocampus, and decreased mortality in T2DM rats. The Morris water maze test indicated that YGJ reduced the escape latency and increased platform crossing frequency, thereby improving cognitive function in T2DM rats. Furthermore, YGJ regulated the abundance of microorganisms associated with bile acid metabolism, including Romboutsia, Bacteroides, Turicibacter, Blautia, and Ruminococcus, thus regulating bile acid metabolism in T2DM rats. Additionally, YGJ also regulated bile acid metabolism by regulating intestinal FXR, PXR, VDR and TRG5 receptors. YGJ can alleviate glucose homeostasis, insulin sensitivity, lipid metabolism, neuroinflammation, cognitive function, as well as remodel intestinal flora and BA composition in CDT2DM rats, which is a potential complementary and alternative therapy for the prevention and treatment of CDT2DM. These effects may be associated that YGJ regulates the structure of intestinal flora and BA metabolism, and inhibits intestinal BA receptors FXR, PXR, TGR5, and VDR.

Effectiveness and Safety of Metformin, Teneligliptin, and Glimepiride Combination Therapy in Type 2 Diabetes: A Quasi Experimental Clinical Trial.

Type 2 Diabetes Mellitus (T2DM) accounts for more than 95% of all diabetes cases and is a leading cause of disability and death. This study aimed to evaluate the effectiveness and safety of a combination therapy involving metformin, teneligliptin, and glimepiride in patients diagnosed with T2DM. The present quasi-experimental clinical trial involved 300 adult T2DM patients. They were divided into three groups: Group 1 (Metformin; n=100), Group 2 (Metformin + Teneligliptin; n=100), and Group 3 (Metformin + Teneligliptin +; n=100). Along with demographic data, we collected information on HbA1c, FBS, and PPBS levels, as well as fasting insulin, CPeptide, HOMA-IR, QUICKI-IR, and lipid, renal, and hepatic profiles at baseline and after 3, 6, and 12 months. Data analysis was performed using SPSS 21.0 software. A total of 300 patients participated in the study. At the end of 12 months, triple-drug therapy achieved significant glycemic control (HbA1c: 6.56±0.50%; P<0.0001) and reduced FBS (7.6±1.41 mg/dl; P<0.0001), PPBS (9.39±2.14 mg/dl; P<0.0001), and fasting insulin (11.26±2.5 IU; P<0.0001), C-peptide (2.01±2.29 ng/ml; P<0.0001), and insulin resistance by HOMA-IR (3.74±0.7; P<0.0001). Favorable lipid profiles (P<0.0001) were noted versus other groups. Despite renal and hepatic profile variations, values remained within the normal range. The combination of teneligliptin with metformin and glimepiride in T2DM patients demonstrated significant improvements in glycaemic control, reduced insulin resistance, and positive effects on lipid, renal, and hepatic profiles. Importantly, the therapy did not result in serious adverse drug reactions, such as hypoglycemia. We need more RCTs to substantiate these findings.

Suppression of colorectal cancer growth: Interplay between curcumin and metformin through DMT1 downregulation and ROS-mediated pathways.

The rising incidence of colorectal cancer (CRC) poses significant healthcare challenges. This study explored the therapeutic potential of combined curcumin (CUR) and metformin (MET) treatment in CRC models. Our findings indicate that the combination treatment (COMB) effectively downregulates the expression of divalent metal transporter-1 (DMT-1), leading to a reduction in cell proliferation aligned with suppression of the pAKT/mTOR/Cyclin D1 signaling pathway. The COMB increased reactive oxygen species (ROS) production, triggering activation of the NRF2/KEAP1 pathway. This pathway elicits an antioxidant response to manage oxidative stress in CRC cell lines. Interestingly, the response of NRF2 varied between CT26 and HCT116 cells. Moreover, our study highlights the induction of apoptosis and autophagy, as evidenced by upregulations in Bax/Bcl-2 ratios and autophagy-related protein expressions. Notably, the COMB promoted lipid peroxidation and downregulated xCT levels, suggesting the induction of ferroptosis. Ferroptosis has been shown to activate autophagy, which helps eliminate cells potentially damaged by the increased oxidative stress. Furthermore, the COMB effectively diminished the migratory ability of CRC cells. In vivo experiments using CRC-bearing mouse models, the results confirmed the anti-tumor efficacy of the COMB, leading to substantial inhibition of tumor growth without inducing general toxicity. In conclusion, our study suggests that combining CUR with MET holds promise as a potential option for CRC treatment, with critical mechanisms likely involving ROS elevation, autophagy, and ferroptosis.

Red, green, and blue model assessment and AQbD approach to HPTLC method for concomitant analysis of metformin, pioglitazone, and teneligliptin

BackgroundThe CDSCO of India has authorized a combination of metformin hydrochloride, teneligliptin hydrochloride, and pioglitazone hydrochloride for the treatment of insulin-independent diabetes. For the purpose of estimating metformin, teneligliptin, and pioglitazone combinations as well as individual commercial formulations, there are a plethora of publicly accessible chromatographic techniques. More importantly, the development of these chromatographic procedures has included the use of chemical solvents that are dangerous to both animals and the environment.ObjectivesHowever, to date, there has been no documented chromatographic technique that can concomitantly estimate various commercial formulations of drugs under study employing a uniform chromatographic condition and environmentally friendly solvents. In order to concomitantly estimate drugs under study utilizing unified chromatographic conditions, a green HPTLC method was developed.MethodThe AQbD approach was used to carry out the method development. To determine the most important method parameters and response variables, the analytical risk assessment was conducted using the risk priority number ranking and screening approach. Critical method parameters and response variables were modeled using the response surface modeling approach, which relies on the central composite design. Optimal ranges for the intended method operable design region were determined, and control strategy was framed. The chromatographic separation was carried out on preparative TLC plate precoated with silica gel G-60 F254 using 1.0%W/V ammonium acetate in ethanol: water: triethylamine (6.5:0.4:0.6, V/V) as mobile phase. The detection of the anti-diabetic drugs under study was carried out at 267 nm wavelength.ResultsThe linearity of metformin, teneligliptin, and pioglitazone was found to be 5000–25000 ng/band, 200–1000 ng/band, and 150–750 ng/band, respectively. The %RSD for robustness and precision study was found to be less than 2.0%. The %recovery of method was found to be 98–102%. The assay results were shown to be in compliance with respective labeled claims of anti-diabetic medications when the suggested method was used for concurrent analysis of several formulations and combinations of drugs under study.ConclusionThe suggested technique was evaluated utilizing red–green–blue model scoring tools. The suggested technique was determined to be precise, accurate, rapid, cost-effective, and easy to apply for the estimation of drugs under study.

Comparative effects of metformin and varying intensities of exercise on miR-133a expression in diabetic rats: Insights from machine learning analysis

This study investigated the effects of metformin, high-intensity interval training (HIIT), and moderate-intensity continuous training (MCT) on miR-133a expression in a diabetic rat model. miR-133a, a microRNA associated with skeletal muscle insulin resistance, served as a key indicator of treatment efficacy. Diabetic rats exhibited elevated miR-133a levels compared to healthy controls. Both HIIT and MCT, alone and in combination with metformin, significantly reduced miR-133a expression. Importantly, the combination of HIIT and metformin demonstrated the most potent effect, reducing miR-133a levels more than other treatments. We used the CatBoost algorithm to develop a predictive model for miR-133a expression based on metabolic parameters. The model accurately predicted miR-133a levels using body weight, blood glucose, insulin levels, and cholesterol metrics. The findings suggest a potential clinical strategy combining metformin and exercise, with miR-133a potentially serving as a biomarker for personalized diabetes management.

Analysis of factors related to venous thrombosis after ankle fracture combined with type 2 diabetes mellitus applying tourniquet surgery.

The objective was to study the risk factors of venous thrombosis after ankle fracture with type 2 diabetes mellitus surgery using a tourniquet and to assess the effect of ischemic preconditioning and metformin combination therapy in preventing thrombosis. One hundred eighty patients with ankle fractures combined with type 2 diabetes mellitus treated with lower extremity tourniquet surgery between January 2020 and December 2023 were analyzed. Based on postoperative color Doppler ultrasound of both lower extremities, the patients were divided into thrombus-positive and negative groups. Multifactorial logistic regression analysis was utilized to determine the high-risk factors for venous thrombosis and construct a prediction model. There were 64 cases in the positive group and 116 cases in the negative group. The differences between the 2 groups in gender, age, fracture site, preoperative glycosylated hemoglobin, thromboelastography parameters, duration of surgery, D-dimer level at 1-week postoperatively, and thromboelastography K, α, and MA values were not statistically significant (P > .05); however, there was no statistically significant difference in the preoperative D-dimer level, tourniquet duration, bleeding volume, thromboelastography R-value at 1-week postoperatively, and ischemic preconditioning in combination with metformin treatment patient There was a significant difference in the proportion (P < .05). Multifactorial logistic regression analysis showed that preoperative high D-dimer, prolonged tourniquet application, massive bleeding, and increased thromboelastography R-value at 1-week postoperatively were independent risk factors, and ischemic preconditioning combined with metformin was a protective factor. Preoperative high D-dimer, prolonged tourniquet application, massive bleeding, and increased thromboelastography R-value at 1-week postoperatively were independent risk factors for postoperative venous thrombosis in patients with ankle fracture with type 2 diabetes mellitus and ischemic preconditioning combined with metformin treatment was a protective measure, and the prediction model is valuable in guiding clinical thrombosis risk assessment.

Analytical Techniques for the Determination of Metformin and its Combinations with Oral Antidiabetic Agents in Pharmaceutical Dosage Forms: Combinations with Sulphonylurea Antidiabetic Drugs

The sulfonylurea class of antidiabetic agents includes a range of closely related compounds, allowing for similar analytical approaches when combined with metformin. This article provides a comprehensive review of published methods for determining sulfonylureas and metformin combinations in bulk and pharmaceutical preparations. Various techniques such as high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC), capillary zone electrophoresis (CZE), and spectrophotometric methods have been widely used for these compounds, yielding reliable results. Additionally, the article discusses the number of citations for each method and its specific purpose, offering critical commentary. Keywords: metformin; sulphonylureas; combination; determination; analytical techniques

Effectiveness of metformin in combination with intranasal insulin for the treatment of metabolic and hormonal disturbances in adult male rats with metabolic syndrome induced by impaired breastfeeding

BACKGROUND: Limiting or temporally stopping breastfeeding can lead to the development of metabolic syndrome in adulthood, which requires the development of approaches for its prevention and correction. One such approach is treatment with metformin or intranasal insulin. Since the targets of these agents differ and may complement each other, it has been suggested that their combined use could be effective. AIM: To study the effect of a four-week co-administration of metformin (orally, 120 mg/kg/day) and intranasal insulin (1.2 IU/kg/day) in male rats with metabolic syndrome, induced by breastfeeding disruption on postnatal days 19–21, on their metabolic and hormonal parameters. MATERIALS AND METHODS: The study treatment was compared with monotherapy using the same drugs. RESULTS: It was found that adult male rats with disrupted breastfeeding developed obesity, dyslipidemia, hyperleptinemia, impaired glucose tolerance, and a reduction in the number of β-cells and the area of pancreatic islets, which are characteristic of metabolic syndrome. Long-term treatment with metformin and its combination with intranasal insulin partially or fully normalized body weight, abdominal fat, and metabolic and hormonal parameters, with the restorative effect of combination treatment on such parameters as body weight, fat mass, glucose tolerance, and blood glycated hemoglobin levels being more pronounced than with metformin alone. CONCLUSIONS: The results of the study support the use of a combination of metformin and intranasal insulin to normalize metabolic and hormonal parameters in metabolic syndrome induced by breastfeeding disruption in early days of life.

Combined metformin and simvastatin therapy inhibits SREBP2 maturation and alters energy metabolism in glioma

This study aims to explore the inhibitory effects of combined metformin and simvastatin therapy on the malignant progression of glioma. The research specifically examines how the maturation of SREBP2 as a transcription factor affects the expression of GLUT1 and GLUT6 in glioma cells. Additionally, it investigates the impact of this combination therapy on the biological functions and energy metabolism of glioma cells. To assess the functions of GLUT1/6, sh-GLUT1/6 plasmids were employed. The study determined the half-maximal inhibitory concentrations (IC50) of metformin and simvastatin using the CCK-8 assay. Subsequently, the effects of these drugs on glioma metabolism, proliferation, and apoptosis were explored in vitro and in vivo, using drug concentrations significantly lower than their respective IC50 values. The impact of drug treatment on GLUT1/6 and SREBP2 expression levels was also evaluated. The study elucidated the significant impact of GLUT1/6 on glioma cell functions, resulting in decreased glucose uptake. Moreover, it unveiled the regulatory role of SREBP2 in GLUT1 and GLUT6 transcription, alongside revealing differential expression of SREBP2 precursor and mature forms within gliomas. Following combined drug therapy, GLUT1/6 expression decreased, while the precursor form of SREBP2 increased, and mature SREBP2 reduced. This dual-drug treatment effectively modulated glioma cell energy metabolism. Subsequent in vivo experiments affirmed the augmented anti-tumor efficacy of combined drug therapy. Specifically, the synergistic action of metformin and simvastatin reshaped glioma metabolism, curbed malignant proliferation, promoted apoptosis, and demonstrated superior anti-tumor effects both in vitro and in vivo compared to individual administration of metformin or simvastatin. Importantly, the combination therapy achieved these effects at lower doses, rendering it a safer treatment option.