Combination Of Metformin Research Articles

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.

Correction of the clinical course of non-alcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes

Background. The relevance of finding optimal methods to treat patients with a comorbid non-alcoholic steatohepatitis (NASH) that developed against the background of type 2 diabetes mellitus (T2DM) is due to the fact that these diseases have a number of common cause-and-effect mechanisms, and if diabetic kidney disease (DKD) develops, also mutual burden mechanisms. The purpose of the study was to find out the possible influence of a combination of metformin, rosuvastatin, essential phospholipids and quercetin on the clinical course of non-alcoholic steatohepatitis, diabetic kidney disease, type 2 diabetes mellitus, as well as on the state of the blood lipids, parameters of carbohydrate metabolism compensation, the degree of insulin resistance, which are factors for the progression of NASH and diabetic kidney disease. Materials and methods. Studies were conducted on the dynamics of treatment in 60 patients with NASH, T2DM and DKD stage I–III: 48 (80.0 %) of them had mild NASH, and 12 (20.0 %) had moderate NASH. A comorbid disease in 100 % of patients was moderate type 2 diabetes: 15 (25.0 %) people were diagnosed with diabetes in the stage of compensation, 45 (75.0 %) had subcompensated disease. Results. The positive effect of quercetin was noted by us in relation to the content of low-density lipoprotein cholesterol in the blood that was increased by 1.8 times (p &lt; 0.05) before the treatment: a decrease after it was 1.7 times (p &lt; 0.05) in group 2 and 1.3 times (p &lt; 0.05) in group 1. Comprehensive therapy with the inclusion of quercetin contributed to a probable increase in anti-atherogenic high-density lipoprotein (by 1.3 times, p &lt; 0.05) with the normalization of the indicator after the treatment, while traditional therapy in this contingent did not lead to any probable changes. Conclusions. The combination therapy for type 2 diabetes mellitus and NASH with the addition of quercetin contributed to the elimination of the main clinical and laboratory symptoms of NASH exacerbation, a probable reduction in the liver inflammation (a decrease in markers of cytolysis, mesenchymal inflammation), reversal of hepatic steatosis due to the optimization of cholesterol and triacylglycerols in the blood, a probable increase in high-density lipoproteins, normalization of glycemia, reduction of insulinemia, a decrease in the degree of insulin resistance. The effectiveness of treatment for DKD was also increased: the rate of proteinuria and the degree of hypercreatinemia decreased, and the glomerular filtration rate increased.

The synergistic anti-Warburg efficacy of temozolomide, metformin and epigallocatechin gallate in glioblastoma

An important hallmark of glioblastoma aggressiveness is its altered metabolism of glucose. This metabolic shift wherein the tumor cells employ aerobic glycolysis regardless of oxygen availability via reprogramming of mitochondrial oxidative phosphorylation is known as the Warburg effect. Previous literatures have linked this metabolic reprograming to tumor progression and glioblastoma cell proliferation making it a key target for targeted drug therapy. Based on this lacuna, the current study aimed to explore the therapeutic efficacy of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in attenuating Warburg effect and glucose uptake in glioblastoma both in vitro and in vivo. Our results showed that the triple-drug combination had significantly reduced glucose uptake and reversed the Warburg effect in glioblastoma cells and in the glioma-induced xenograft rat model. Thus, the triple-drug combination would serve as an effective therapeutic regime to hamper glioblastoma progression via altering glucose metabolism and improving the overall prognosis in patient setting.

Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines.

Ovarian cancer (OC) remains one of the leading causes of cancer-related mortality among women. Targeting the insulin-like growth factor 1 (IGF-1) signaling pathway has emerged as a promising therapeutic strategy. Linsitinib, an IGF-1 receptor (IGF-1R) inhibitor, has shown potential in disrupting this pathway. Additionally, metformin, commonly used in the treatment of type 2 diabetes, has been studied for its anti-cancer properties due to its ability to inhibit metabolic pathways that intersect with IGF-1 signaling, making it a candidate for combination therapy in cancer treatments. This study explores the anti-cancer effects of linsitinib and metformin on OVCAR3 cells by the suppression of the IGF-1 signaling pathway by siRNA-mediated IGF-1 gene silencing. The goal is to evaluate their efficacy as therapeutic agents and to emphasize the critical role of this pathway in OC cell proliferation. Cellular viability was evaluated by resazurin-based assay, and apoptosis was assessed by flux cytometry. The results of this study indicate that the combination of linsitinib and metformin exhibits an antagonistic effect (obtained by SynergyFinder 2.0 Software), reducing their anti-neoplastic efficacy in OC cell lines. Statistical analyses were performed using ordinary one-way or two-way ANOVA, followed by Tukey's or Šídák's multiple comparison tests. While linsitinib shows promise as a therapeutic option for OC, further research is needed to identify agents that could synergize with it to enhance its therapeutic efficacy, like the combination with standard chemotherapy in OC (carboplatin and paclitaxel).

Фиксированная комбинация метформина и ситаглиптина: аддитивность эффектов для успешного управления гликемией и сердечно-сосудистыми рисками у пациентов с сахарным диабетом 2 типа

Various classes of drugs are used for the treatment of type 2 diabetes mellitus, both in monotherapy and in combination. In elderly patients, people at high risk of hypoglycaemia and at the onset of the disease it is recommended to prescribe a combination of metformin and dipeptidyl peptidase 4 inhibitors (glyptins). This article reviews the mechanisms of hypoglycaemic action of drugs, pleiotropic effects of metformin and sitagliptin, and the efficacy of the combination of these drugs against type 2 diabetes mellitus, lipid metabolism disorders and oxidative stress.

The combination of metformin and high glucose increased longevity of Caenorhabditis elegans a DAF-16/FOXO-independent manner: cancer/diabetic model via C. elegans.

Sedentary lifestyles and diets with high glycemic indexes are considered to be contributing factors to the development of obesity, type 2 diabetes in humans. Metformin, a biguanide medication commonly used to treat type 2 diabetes, has been observed to be associated with longevity; however, the molecular mechanisms underlying this observation are still unknown. The effects of metformin and high glucose, which have important roles in aging-related disease such as diabetes and cancer, were studied in lin-35 worms because they are associated with cancer-associated pRb function in mammals and have a tumour suppressor property. According to our results, the negative effect of high glucose on egg production of lin-35 worms was greater than that of N2 worms. High glucose shortened lifespan and increased body length and width in individuals of both strains. Metformin treatment alone extended the lifespan of N2 and lin-35 worms by reducing fertilization efficiency. However, when metformin was administered in the presence of high glucose, the lifespan of lin-35 worms was clearly longer compared to N2 worms. Additionally, we conclude that glucose and metformin in lin35 worms can extend life expectancy through a DAF-16/FOXO-independent mechanism. Furthermore, the results of this study will provide a new perspective on extending mammalian lifespan through the model organism C. elegans.

Gestational diabetes and pregnancy outcome in Kurdish, Somali and general population in Finland

Abstract Gestational diabetes (GDM) increases the risk of type II diabetes and cardiovascular morbidity later in life but GDM incidence in women from different cultural backgrounds varies. This study aims to examine treatment of GDM and pregnancy outcomes in Somali, Kurdish and general population women. Patient data of 312 Kurdish, 254 Somali and 508 general population women was collected from Turku University Hospital records from 2008 to 2019. The general population was selected by randomization with matching year, BMI, age, and parity. Singleton deliveries after 34th gestational week with no prior diabetes mellitus were included. Descriptive and comparison analyses (SPSS, version 29.0) were used to identify associations between ethnic background and pregnancy outcomes in women with GDM. The incidence of GDM was 22 % (CI 95 % 17-27) in Somali, 36 % (CI 95 % 31-42) in Kurdish, and 16 % (CI 95 % 13-19) in the general population women. Kurdish women had medication for GDM more often (43 % CI 95 % 34-53) than the Somali (22 % CI 95 % 11-33) and general population women (18 % CI 95 % 9-26). Metformin was more commonly used among Kurdish (30 % CI 95 % 22-39) compared to the general population (12 % CI 95 % 4-18) and Somali women (13 % CI 95 % 4-22). There was no difference in insulin or combined metformin and insulin treatment between the groups. In GDM group, vaginal deliveries were more common in general population (89 % CI % 81-95) than in Somali women (67 % CI % 64-81). Induction of labour (indication GDM or other) and instrumental vaginal delivery rates were similar between the groups. Newborns of all Somali women had a lower weight (SD -0.3 CI 95 % -0.7 - -0.2) compared to the general population (SD 0 CI 95 % -0.1 - 0.3). The prevalence of GDM was increased and dietary treatment decreased in Kurdish women compared to the general population in Finland. In the future, the treatment of GDM should be adjusted to better optimize the care for different cultural background women. Key messages • Kurdish women have increased incidence of GDM and less dietary treatment compared to the general population with similar risk factors. The pregnancy outcomes remain good in all groups. • With Somali women, the birth weight of the child is lower despite GDM status. This might direct clinicians to underestimate the effect of GDM when considering individual treatment.

Combination therapy of systemic and local metformin improves imiquimod-induced psoriasis-like lesions with type 2 diabetes: the role of AMPK/KGF/STAT3 axis.

Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO). We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM. Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod. Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression. Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects.

Effects of metformin and curcumin in women with polycystic ovary syndrome: A factorial clinical trial

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder in women, associated with dyslipidemia, insulin resistance, and hormonal imbalances. Metformin and curcumin have shown promise in improving these metabolic and hormonal parameters individually, but their combined effects in PCOS remain unclear. MethodsWe conducted a randomized, double-blind, placebo-controlled, 12-week factorial trial involving 200 women with PCOS. Participants were randomly assigned in a 1:1:1:1 ratio to receive metformin (500-mg/8 h) + placebo, nanocurcumin soft gel capsule (80-mg/8 h) + placebo, metformin (500-mg/8 h) + nanocurcumin (80-mg/8 h), or double placebo. Lipid profiles, glucose metabolism markers, hormonal parameters, body weight, and body mass index (BMI) were assessed at baseline and week 12. ResultsThe combination of metformin and curcumin demonstrated significant improvements in lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI compared to individual agents or placebo. Greater reductions in low-density lipoproteins (LDL) cholesterol, total cholesterol (TC), and triglyceride (TG) levels were observed with the combination therapy, along with increased high-density lipoproteins (HDL) cholesterol. Additionally, the combination therapy significantly improved markers of glucose metabolism and showed synergistic effects in reducing body weight and BMI. Reductions in testosterone and improvements in Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) levels were also observed with combination therapy. ConclusionThe combination of metformin and curcumin demonstrates superior efficacy in improving lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI in women with PCOS compared to individual agents or placebo. This highlights the potential synergistic effects of combining these agents for the management of PCOS.

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial

ObjectiveTo evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with...

Metformin in Overcoming Enzalutamide Resistance in Castration-Resistant Prostate Cancer.

Androgen deprivation is the standard treatment for prostate cancer (PCa) patients. However, the disease eventually progresses as castration-resistant PCa (CRPC). Enzalutamide, an AR inhibitor, is a typical drug to treating CRPC and due to continuous reliance on the drug, can lead to Enzalutamide-resistance (ENZ-r). This highlights the necessity for developing novel therapeutic targets to combat the gain of resistance. Metformin has been recently investigated for its potential anti-tumorigenic effects in many cancer types. In this study, we used enzalutamide and metformin in combination to explore the possible rescued efficacy of enzalutamide in the treatment of ENZ-r CRPC. We first tested the effects of this combination treatment on cell viability, drug synergy, and cell proliferation in ENZ-r CRPC cell lines. After combination treatment, we observed a decrease in cell proliferation and viability as well as a synergistic effect of both enzalutamide and metformin in vitro Following these results, we sought to explore how combination treatment effected mitochondrial fitness utilizing mitochondrial stress test analysis and mitochondrial membrane potential (MMP) shifts due to metformin's action in inhibiting Complex I of oxidative phosphorylation. We employed 2 different strategies of in vivo testing using 22Rv1 and LuCaP35CR xenograft models. Finally, RNA sequencing revealed a potential link in the downregulation of Ras/MAPK signaling following combination treatment. Significance Statement Increasing evidence suggests that oxidative phosphorylation might play a critical role in the development of resistance to cancer therapy. We showed that targeting oxidative phosphorylation with metformin can enhance the efficacy of enzalutamide in castration-resistant prostate cancer in vitro.