Dose Of Metformin Research Articles

Impact Of High Dose Metformin Versus Teneligliptin as add together on to Metformin on Glycemic Control of T2DM Patients

Introduction: Hyperglycaemia and abnormalities in simple carbohydrate, fat and protein metabolism are the characteristic feature of the metabolic disorder, Diabetes Mellitus. Diabetes mellitus treatment is achieved by modifications in diet, sleep pattern, regular physical activity followed by addition of anti-hyperglycemic drugs like metformin if HbA1C levels stays more than 7.0%.Materials and Methods The study period was from April 2019 – September 2019. The total duration of study was 24 weeks. Total 160 patients were screened; among them 100 participants were selected as per the inclusion criteria. Out of 100 patients, only 91 patients have completed the study. Conclusion To conclude DPP-4 inhibitor Teneligliptin 20mg OD exemplifies to be a pertinent add-on to Metformin 500mg BD to enhance the glycaemic control and could be an operative and reliable medication preference in T2DM through decent patient acceptability.

Impact of High Dose Metformin Versus Teneligliptin as add together on to Metformin on Glycemic Control of T2DM Patients

Introduction: Hyperglycaemia and abnormalities in simple carbohydrate, fat and protein metabolism are the characteristic feature of the metabolic disorder, Diabetes Mellitus. Diabetes mellitus treatment is achieved by modifications in diet, sleep pattern, regular physical activity followed by addition of anti-hyperglycemic drugs like metformin if HbA1C levels stays more than 7.0%.Materials and Methods The study period was from April 2019 – September 2019. The total duration of study was 24 weeks. Total 160 patients were screened; among them 100 participants were selected as per the inclusion criteria. Out of 100 patients, only 91 patients have completed the study. Conclusion To conclude DPP-4 inhibitor Teneligliptin 20mg OD exemplifies to be a pertinent add-on to Metformin 500mg BD to enhance the glycaemic control and could be an operative and reliable medication preference in T2DM through decent patient acceptability.

P-427 Pregnancy outcomes following recurrent first-trimester miscarriage: a retrospective cohort study

Abstract Study question What are the subsequent pregnancy outcomes (livebirths, miscarriages or other adverse pregnancy outcomes) in a cohort of women with recurrent miscarriage (RM)? Summary answer The overall live birth rate in women with RM was 62% (466/748), falling to 44% in women aged >40 and 54% in women with infertility. What is known already RM affects approximately 1% of women of reproductive age. RM is recognized as a prognostic indicator for subsequent pregnancies and adverse pregnancy outcomes including ante-partum hemorrhage, diabetes, preterm birth, small for gestational age and perinatal death. While RM has known associations with advanced maternal age, obesity, diabetes, thyroid dysfunction and endometriosis, approximately 50% of women/couples will be left without an explanation for their pregnancy loss, even after completing investigations. Study design, size, duration A retrospective cohort study was undertaken to identify subsequent pregnancy outcomes in women with RM, where RM referral criteria are 3 consecutive first-trimester miscarriages. Women attending the pregnancy loss clinic at a tertiary university hospital in the Republic of Ireland over a 12-year period (2008 - 2020) with a confirmed diagnosis of primary or secondary first-trimester RM were eligible for inclusion. In total, 923 charts were identified for review against the eligibility criteria. Participants/materials, setting, methods Women with non-consecutive first trimester miscarriages or ectopic pregnancy were excluded. Epidemiological and clinical information was gathered from paper and electronic medical records. Data were analysed descriptively using SPSS (Version 27). Main results and the role of chance Of 748 women identified, 332(44%) had primary RM, 416(56%) had secondary RM. The median age was 36(range 19-47) years with 12% aged under 29 and 64% of women aged ≥35. 142(19%) had a history of infertility with 43(5.7%) attending for ART. 12% of women had anti-nuclear antibodies(89/742), 8% had abnormal thyroid function tests(60/742), 4.7% were heterozygous carriers of the Factor V Leiden gene mutation(35/737), 1.5% had positive anti-cardiolipin antibodies(11/733), 2% were carriers of a Prothrombin gene mutation(7/343) and 1% had elevated HbA1c levels(7/742). Fetal karyotype was recorded in 141 pregnancies, with 111 abnormal results(78%;111/141). Trisomy(T) 16 was most common(17/111; 15%) followed by T21 and T22(n = 14; 13%). Parental karyotyping of 697 sets of parents identified 28 balanced translocations(4%; 28/697). Prescribed pharmacological treatments included high dose folic acid(75%; n = 548/728), aspirin(96%; 696/726), progesterone (52%; 389/728), tinzaparin(24%; 175/727), prednisolone(4%; 28/726), metformin(2%; 12/727) and hydroxychloroquine(1%; 7/727). 573 women had a subsequent pregnancy (76.6%); 359(62%; 359/573) had a live birth, 190 had a miscarriage(33%) and 18(3%) had an adverse pregnancy outcome such as ectopic pregnancy, stillbirth or second-trimester miscarriage. Including successive pregnancies over the study period, the overall live birth rate was 62%(466/748), falling to 44% in women aged >40 and 54% in women with infertility. Limitations, reasons for caution This work covers a 12-year period, and while the RM clinic staffing is largely unchanged, some changes in management of RM patients has occurred in this time, reflecting up-to-date evidence and greater public awareness. Furthermore, the adoption of an electronic health chart in 2017 may have affected data availability. Wider implications of the findings Our findings confirm RM occurs more frequently in women aged >35. Aneuploidy remains a leading cause of miscarriage. Age is a prognostic indicator for livebirth after RM. These findings will facilitate counselling in this cohort. The substantial rates of prescribed medications and infertility in women with RM merit further exploration. Trial registration number N/A

Metformin Promotes Axonal Regeneration and Functional Recovery in Diabetic Rat Model of Sciatic Nerve Transection Injury.

In our previous study, metformin was able to promote nerve regeneration after sciatic nerve crushing in rats under diabetic conditions. However, a crush injury also has a strong ability to spontaneously recover. Therefore, in our present study, a model of transection injury of the sciatic nerve in diabetic rats was utilized to detect whether metformin could still promote nerve regeneration. Diabetes was induced via an injection of 50 mg/kg of streptozotocin in rats. After transection injury of the sciatic nerve, the rats were randomly divided into a high-dose metformin group (500 mg/kg/d), mid-dose metformin group (200 mg/kg/d), low-dose metformin group (30 mg/kg/d) and control group (normal saline). The metformin or normal saline was intraperitoneally injected for 4 weeks. Then, behavioral, electrophysiological and morphometric analyses were performed. The results showed that metformin could significantly promote functional restoration and axonal regeneration of the sciatic nerve after transection injury under diabetic conditions. Furthermore, high doses and middle doses of metformin presented more of this ability than a low dose of metformin. In conclusion, metformin is able to accelerate sciatic nerve repair after transection injury under diabetic conditions, showing the therapeutic potential of metformin in the management of nerve injuries during diabetes mellitus.

Association of GLP1R Polymorphisms With the Incretin Response.

Polymorphisms in the gene encoding the glucagon-like peptide-1 receptor (GLP1R) are associated with type 2 diabetes but their effects on incretin levels remain unclear. We evaluated the physiologic and hormonal effects of GLP1R genotypes before and after interventions that influence glucose physiology. Pharmacogenetic study conducted at 3 academic centers in Boston, Massachusetts. A total of 868 antidiabetic drug-naïve participants with type 2 diabetes or at risk for developing diabetes. We analyzed 5 variants within GLP1R (rs761387, rs10305423, rs10305441, rs742762, and rs10305492) and recorded biochemical data during a 5-mg glipizide challenge and a 75-g oral glucose tolerance test (OGTT) following 4 doses of metformin 500 mg over 2 days. We used an additive mixed-effects model to evaluate the association of these variants with glucose, insulin, and incretin levels over multiple timepoints during the OGTT. During the OGTT, the G-risk allele at rs761387 was associated with higher total GLP-1 (2.61 pmol/L; 95% CI, 1.0.72-4.50), active GLP-1 (2.61 pmol/L; 95% CI, 0.04-5.18), and a trend toward higher glucose (3.63; 95% CI, -0.16 to 7.42 mg/dL) per allele but was not associated with insulin. During the glipizide challenge, the G allele was associated with higher insulin levels per allele (2.01 IU/mL; 95% CI, 0.26-3.76). The other variants were not associated with any of the outcomes tested. GLP1R variation is associated with differences in GLP-1 levels following an OGTT load despite no differences in insulin levels, highlighting altered incretin signaling as a potential mechanism by which GLP1R variation affects T2D risk.

Jiangtang Tongmai Prescription Reduced Diabetic Lung Injury Through SnoN and TGF-β1/Smads Signaling Pathway.

By establishing a rat diabetes model in rats with intervening treatment by Jiangtang Tongmai Prescription (JTTMP), this study explored the restorative pairing effect of JTTMP on diabetic lung injury. The model of type II diabetes model was used to establish the rat diabetes model, using a high-fat diet and streptozotocin (STZ) induction. Different doses of JTTMP and metformin were administered as a therapeutic to intervene, and blood was collected to assess the blood glucose level of each group of rats. HE (Hematoxylin and eosin (H&E) staining was performed to detect the morphological changes in rat lung tissue and enzyme-linked immunoassay ELISA was used to detect and quantify the expression of interleukin (IL)-6, TNF tumor necrosis factor-ɑa, and IL-1β in serum and the lung tissue of each group of rats. The level expression of TGF-β1 [transforming growth factor (TGF)-β1), SnoN (transcriptional co-repressor Ski-N terminal (SnoN)], Smad2, Smad3, Smad7, and other signaling pathway proteins were assessed by Western blot. In comparison with the normal control (NC) group, rats in the diabetes model (DM) group lost weight and showed significantly increased blood sugar levels. The levels of TGF-β1 and Smad2/3 were increased in the DM group but Smad7 decreased. After 8 weeks of JTTMP intervention, the level of TGF-β1 and Smad2/3 decreased but Smad7 increased, blood sugar decreased significantly and the expression of inflammatory factors in lung tissue decreased. Therefore, JTTMP may activate SnoN and the downstream TGF-β1/Smads signaling pathway to repair diabetic lung injury, which suggests its application has potential for future clinical treatment of diabetes with lung injury.

Chlorogenic acid improves anti-lipogenic activity of metformin by positive regulating of AMPK signaling in HepG2 cells.

Metformin improves lipid profile, however, combination therapy is developing to increase its effectiveness and reduce the deleterious effects of metformin. Chlorogenic acid (CGA) has exhibited lipid-lowering effects. This study aimed to investigate the combined effect of metformin and CGA on lipid accumulation, as well as to elucidate the engaged mechanism in HepG2 cells. To find the non-lethal doses of metformin and CGA, MTT assay was performed. High Glucose (HG) at 33 mM was used to induce lipogenesis in HepG2 cells. Following treatment with different concentrations of metformin and CGA, total lipid content (Oil Red O-staining), triglyceride level, the genes expression of SREBP-1c and FAS, and phosphorylation of AMPK and ACC were measured. Both Metformin and CGA decreased HG-induced lipid accumulation individually, by decreasing total lipid content and triglyceride level. The lowest effective doses of metformin and CGA were 0.25 mM and 5 μM, respectively, which significantly reduced SREBP-1c and FAS genes expression. The combination of these concentrations reinforced these effects. The phosphorylation of AMPK and ACC were more increased by metformin in combination with CGA than both individually. Our findings suggest that CGA synergistically enhances metformin lipid reducing action via the regulating of involved factors in fatty acid synthesis. Therefore, co-administration of metformin with CGA may have further medical value in treating lipid metabolism disorders.

Abstract 502: The association of metformin dose and cancer survival in older adults with advanced cancer: SEER-Medicare analysis

Abstract Cancer and type 2 diabetes (T2DM) are common diseases that have serious health consequences. T2DM is known to increase the risk for the development of many of the most common cancers. Metformin, one of the most commonly used drugs to treat T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on OS in patients with advanced cancer. We examined the relationship between metformin dose and OS in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. Methods: We used a retrospective study design with cox proportional hazards regression analysis of the 2007-2016 of the Surveillance Epidemiology and End Results-Medicare dataset. Results: A total of 7,725 patients with T2DM and a least one targeted cancer was included in the analysis. Of those patients, 38.5% had been prescribed metformin. Patients who used metformin had significantly better OS in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69-0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; p < 0.001). The OS between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93-1.08; p=0.90). Conclusions: Metformin use, regardless of dose, increases OS in older adults with advanced cancer. Additionally, OS was not significantly different across race or ethnicity. Citation Format: Lisa Scarton, Ara Jo, Zhigang Xie, LaToya J. O’Neal, Juan M. Pena, Thomas J. George, Jiang Bian. The association of metformin dose and cancer survival in older adults with advanced cancer: SEER-Medicare analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 502.

Effect of Vitamin B12 supplementation on the Diabetic Peripheral Neuropathy- a Review

Neuropathic pain is the unpleasant sensation due to lesion of nerves. It is common in patients with diabetes as fluctuations in blood glucose take a toll on the nervous system. Furthermore, high doses of metformin for the long duration in patients, with type 2 diabetes are found to interfere with the normal metabolism of the vitamin B12 in body that leads to its deficiency. Vitamin B12 is a water soluble vitamin found in our body responsible for the methylation, thus has a role in the myelin sheath and DNA synthesis. Deficiency of vitamin B12 has debilitating effect on the nerves which results in neuropathy. Various studies have been carried out to study whether Vitamin B12 has an effect on the nervous regeneration or can its use improve the diabetic or metformin induced neuropathy? In this paper, up-to-date evidence for effect of vitamin b12 supplementation on diabetic peripheral neuropathy has been studied and evaluated.

The effect of in vitro exposure to certain metformin doses on the motility of human spermatozoa

Metformin is an anti-hyperglycemic medication used to treat type 2 diabetes mellitus. Regardless of its anti-diabetic effect, metformin has a non-genomic action and it could be a beneficial additive to treat the sperm which considered as transcriptionally dormant cell and also a molecule that could rapidly adjust the metabolism of spermatozoa to adapt it to the surrounding environment. Sixty-four normozoospermic semen sample included in the study. Each sample incubated for 30 minutes with metformin (2.5 and 0.5 µM) and SFA was conducted to each sample. There was a significant decrease in total motility (progressive and nonprogressive) in samples incubated with both concentrations compared with the neat samples. While the samples incubated with 0.5 µM shows a lower motility compared with 2.5 µM. Metformin significantly reduced total motility of fresh spermatozoa at both concentrations.

Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain

Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Nevertheless, whether curcumin can exert synergistic analgesia with metformin is still unknown. In the present study, the nature of curcumin-metformin anti-inflammatory interaction was evaluated in in vitro using lipopolysaccharide-induced RAW 264.7 macrophage and BV-2 microglia cells. In both macrophage and microglia, curcumin effectively potentiates the anti-inflammatory effects of metformin, indicating potential synergistic effects in both peripheral and central pathways of pain. The nature of the interaction between curcumin and metformin was further recapitulated using a mouse model of formalin-induced pain. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED50 doses significantly reduced the dose required to produce a 50% effect compared to the theoretically required dose in phase II of the formalin test with a combination index value of 0.24. Besides, the synergistic interaction does not appear to involve severe CNS side effects indicated by no motor alterations, no alterations in short-term and long-term locomotive behaviors, and the general well-being of mice. Our findings suggest that curcumin exerts synergistic anti-inflammation with metformin with no potential CNS adverse effects.

Deficiency of Vitamin B12 in Type 2 Diabetic Patients Receiving Metformin Therapy at HMC Hospital Peshawar

Background: Diabetes mellitus is on the rise at an alarming rate, and it has now become a global issue. Type 2 Diabetic Mellitus is a disease characterized by disturbances in glucose, protein, and fat metabolism. Diabetes has been increasingly common in recent decades, causing significant socioeconomic burden, particularly in poorer countries.
 Objective: To investigate the prevalence of vitamin B12 deficiency in Type 2 diabetes patients taking metformin.
 Methodology: This study was conducted on T2 diabetic patients in the Diabetic Department of Diabetes and Endocrinology HMC Hospital, Peshawar, for a year (10 February 2019 to 12 March 2020). The demographic data of the recruited patients was obtained after they gave their informed written consent. Patients inquired about their metformin use history, dosage, and duration of type 2 diabetes mellitus. A 5cc venous blood sample was taken from the arm and kept at 4 degrees Celsius. Vitamin B12 levels were measured using enzyme-linked immunoassay assays after serum was withdrawn. ELISA was used to determine the Vitamin B12 level in serums.
 Results: A total of 149 people were enrolled in this trial. The patients' average age was 55 years. In this study, there were 67 (38.8%) males and 82 (55.2%) females. The individuals had a 5.12-year history of diabetes mellitus. The average HbA1c level was 8.280.32. The individuals that were included have taken metformin for at least 4.8 years. There were 25 (22.6%) patients using 1000-1500 mg metformin daily, 76 (46.4%) receiving 1500-2000 mg metformin daily, and 48 (40.7%) taking greater than 2000 mg metformin daily. There were 44 patients with a normal BMI, 80 patients who were overweight, and 25 patients who were obese. The average B12 level in the blood was 223pg/ml. Vitamin B12 deficiency was found in 96 (49.1%) of the patients. There was no vitamin B12 deficiency in 53 (45.4%) of the patients.
 Recommendations: It is strongly advised based on the findings of this study that Serum cobalamin levels should be measured in Type II diabetes patients who are taking metformin, and patients should be given R.D.A (Recommended Dietary Allowance) multivitamins to avoid sequaela of cobalamin deficiency.

467-P: The Relationship between Diabetic Peripheral Neuropathy and Metformin Treatment in Type 2 Diabetes Mellitus

Background: Metformin is the first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM) . However, the use of metformin may lead to neuropathy by affecting the absorption of vitamin B12. Our objective was to explore the association between the application of metformin and diabetic peripheral neuropathy (DPN) . Methods: The multicenter randomized cross-sectional study was conducted in 13 hospitals in Beijing from October 2015 to April 2016. T2DM Patients were divided into confirmed DPN group, suspected DPN group and non-DPN group by the five physical examinations (Ankle reflex, acupuncture pain, temperature, vibration, and pressure) . Non-parametric Mann-Whitney test was used for the comparison between non-normally distributed variables between two groups. Chi-square test was used for the comparison of categorical variables. The risk factors of DPN in T2DM Patients were assessed using logistic regression. Results: Compared with patients without metformin, patients taking metformin were more likely to suffer from DPN and suspected DPN (P < 0.0for both) . Similar results were obtained after stratifying the data based on age, BMI, and HbA1c. It was shown that the application of metformin was a risk factor for DPN (OR = 5.06, 95%Cl: 3.90-6.56; P < 0.001) and suspected DPN (OR = 3.58, 95%Cl: 2.78-4.62; P < 0.001) in T2DM patients after the adjustment for age, BMI and HbA1c. In addition, prolonged application of metformin, increased cumulative and single doses would also be associated with the risk of DPN (P < 0.0for all) . Conclusion: The application of metformin was observed relate to DPN in T2DM patients. The vitamin B12 concentration and peripheral nerve function of T2DM patients with the application of metformin should be monitored. Disclosure Q.Pan: None. J.Luo: None. L.Guo: None. Funding National Key R&D Program of China (2020YFC2009006)

Short-term exposure to a clinical dose of metformin increases skeletal muscle mitochondrial H2O2 emission and production in healthy, older adults: A randomized controlled trial.

Metformin is the most commonly prescribed medication to treat diabetes. Emerging evidence suggests that metformin could have off target effects that might help promote healthy muscle aging, but these effects have not been thoroughly studied in glucose tolerant older individuals. The purpose of this study was to investigate the short-term effects of metformin consumption on skeletal muscle mitochondrial bioenergetics in healthy older adults. We obtained muscle biopsy samples from 16 healthy older adults previously naïve to metformin and treated with metformin (METF; 3F, 5M), or placebo (CON; 3F, 5M), for two weeks using a randomized and blinded study design. Samples were analyzed using high-resolution respirometry, immunofluorescence, and immunoblotting to assess muscle mitochondrial bioenergetics, satellite cell (SC) content, and associated protein markers. We found that metformin treatment did not alter maximal mitochondrial respiration rates in muscle compared to CON. In contrast, mitochondrial H2O2 emission and production were elevated in muscle samples from METF versus CON (METF emission: 2.59±0.72 SE Fold, P=0.04; METF production: 2.29±0.53 SE Fold, P=0.02). Furthermore, the change in H2O2 emission was positively correlated with the change in type 1 myofiber SC content and this was biased in METF participants (Pooled: R2=0.5816, P=0.0006; METF: R2=0.674, P=0.0125). These findings suggest that acute exposure to metformin does not impact mitochondrial respiration in aged, glucose-tolerant muscle, but rather, influences mitochondrial-free radical and SC dynamics. NCT03107884, clinicaltrials.gov.

Vitamin B12 Deficiency and Clinical Neuropathy with Metformin Use in Type 2 Diabetes.

Introduction: Type 2 diabetes (T2DM), which is more prevalent (more than 90% of all diabetes cases) and the main driver of the diabetes epidemic, now affects 5.9% of the world’s adult population, with almost 80% of the total in developing countries. At present, 537 million adults (20–79 years) are living with diabetes—1 in 10. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. In India, reports show that 69.2 million people are living with diabetes (8.7%) as per 2015 data. Long-term metformin treatment is a known pharmacological cause of vitamin B12 (Vit B12) deficiency, as was evident within the first 10–12 years after it started to be used. Methods: This was a cross-sectional study conducted in the Postgraduate Department of Medicine in one of the tertiary hospitals in Kashmir. A total of 1600 consecutive patients with T2DM were taken for the study. Out of which 700 patients met the inclusion criteria. These 700 patients were divided into two groups: those taking metformin, and those who were not on metformin. Cumulative metformin doses were recorded in patients taking metformin, using history of dose and duration of treatment. Serum Vit B12 levels were taken for all patients. Based on the results of Vit B12 levels, patients were classified into normal levels (20 pmol/L), possible B12 deficiency (150–220 pmol/l), and definite deficiency (<150 pmol/L). Results: Our results depicted that patients on prolonged metformin therapy showed an increase in Vit B12 deficiency by 11.16%. The prevalence of clinical neuropathy in the metformin-exposed group was 45%, whereas, a prevalence of 31.8% was found in the non-metformin group. The mean age of patients with neuropathy was higher than those without neuropathy (59.01 ± 7.14 vs. 49.95 ± 7.47) (p-value < 0.514, statistically insignificant). Conclusions: In our study, we found that metformin use is associated with Vit B12 deficiency, which is dependent upon the cumulative dose of metformin. Importantly, prolonged metformin use is also associated with an increase in the prevalence of clinical neuropathy.

Focal adhesion kinase–related pathways may be suppressed by metformin in vascular smooth muscle cells in high glucose conditions

IntroductionCardiovascular diseases are known as one of the important causes of death in patients with diabetes mellitus. Metformin is used as an oral medication for reducing blood sugar. In this study, the effects of metformin were investigated on the FAK gene expression levels, pFAK protein values, cell viability and migration rate of VSMCs in high glucose conditions.Materials and methodsThe FAK gene expression levels and pFAK protein values were evaluated in VSMCs treated with different doses of metformin (1, 5 and 7 mM), based on cell viability using RT‐qPCR, western blotting and MTT techniques. The cellular migration was evaluated by scratch assay.ResultsThe FAK gene expression levels reduced significantly in metformin‐treated VSMCs at 24 h and 48 h periods (p < .0008 and p < .0001, respectively). The pFAK protein values reduced significantly at 24 h (5 mM and 7 mM metformin doses) and 48 h periods (p < .001). In agreement with pFAK protein values, cellular migration reduced significantly at 24 h and 48 h periods (p < .001).ConclusionThe results showed that metformin may suppress the proliferation and migration of VSMCs via FAK‐related pathways and may retard the progression of vessel stenosis in diabetes.

Effects of Rosa damascena on reproductive improvement, metabolic parameters, liver function and insulin-like growth factor-1 gene expression in estradiol valerate induced polycystic ovarian syndrome in Wistar rats

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. MethodsAdult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. ResultsCompared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (p < 0.001). ConclusionRD extract seems to have the potential therapeutic effect of alleviating PCOS complications, and IGF-1 signaling may be involved in the beneficial effects of RD on PCOS.

Metformin-associated Lactic Acidosis with Hypoglycemia during the COVID-19 Pandemic

Metformin-associated lactic acidosis (MALA) is an extremely rare but life-threatening adverse effect of metformin treatment. The lifestyle changes associated with the coronavirus disease 2019 (COVID-19) pandemic may increase the potential risk of MALA development in patients with diabetes. We herein report a 64-year-old Japanese man taking a small dose of metformin who presented with MALA accompanied by hypoglycemia secondary to increased alcohol consumption triggered by lifestyle changes during the pandemic. Physicians should prescribe metformin judiciously to prevent MALA development and pay close attention to lifestyle changes in patients at risk for MALA during the COVID-19 pandemic.

Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity.

BackgroundThere are currently relatively few effective pharmacological treatments for obesity, and existing ones may be associated with limiting side-effects. In the search for novel anti-obesity agents, drugs that modify central serotonergic systems have historically proven to be effective in promoting weight loss. Psilocin, which is rapidly metabolized from psilocybin, is an agonist at multiple serotonin receptors. In the present study we assessed the effects of psilocybin and a positive control (metformin) on changes in body weight in a rat model of obesity.MethodsFive groups of adult male rats were pre-conditioned with a cafeteria diet until obese (>600 g) and then treated with either psilocybin (0.1, 1, or 5 mg/kg, i.p.), metformin (300 mg/kg, p.o.) or vehicle control. Treatments were for 27 consecutive weekdays, and body weights and high calorie food intake were recorded daily. Fasting glucose levels were recorded after 11 days of treatment. At the end of treatment rats completed a glucose tolerance test, and multiple fat pads were dissected out to assess adiposity.ResultsThe medium dose psilocybin group had to be terminated from the study prematurely. Both the low and high dose psilocybin groups caused a significant decrease in changes in body weight compared to controls. The metformin group produced a greater decrease in change in body weight than either psilocybin groups or controls. Both high dose psilocybin and metformin decreased consumption of the high calorie diet, and exhibited decreased central adiposity.ConclusionPsilocybin demonstrated modest but significant effects on weight gain. Further study is recommended.

The effect of metformin on vitamin B12 level in pediatric patients.

PurposeMetformin is a common medication for patients with hyperglycemia. In adults, one well-documented side effect of metformin is vitamin B12 deficiency. However, this side effect has rarely been studied in pediatric patients. This study examined the changes of vitamin B12 level in pediatric patients being treated with metformin.MethodsData were collected from pediatric patients (n=151) with at least 3 months of consecutive metformin intake. The effects of dose of metformin on the mean vitamin B12 level were investigated at 6, 12, 24, and 36 months. The effect of compliance of metformin intake on vitamin B12 level also was studied.ResultsThere was no significant decrease in mean vitamin B12 level at 6, 12, 24, or 36 months in patients treated with metformin. Mean vitamin B12 decrease was only noticeable (P<0.05) in patients taking a high dose of metformin with good compliance. Despite this change, the mean vitamin B12 remained well within the normal reference range. Furthermore, of the 151 patients studied, only 1 demonstrated vitamin B12 deficiency after 12 months of treatment. However, his B12 level was normal at 24 and 36 months without any vitamin B12 supplements.ConclusionsOur findings suggest that metformin treatment in children does not cause vitamin B12 deficiency; however, the effect of long-term consistent high-dose treatment on vitamin B12 level remains unknown.