Effect of Metformin on Testosterone Levels in Male Patients With Type 2 Diabetes Mellitus Treated With Insulin

AimTo explore the chronic effects of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).MethodsThis is a secondary analysis of a real-world study evaluating the efficacy and safety of premixed insulin treatment in patients with T2DM via 3-month intermittent flash glucose monitoring. Male patients aged 18-60 who were using metformin during the 3-month study period were included as the metformin group. The control group included males without metformin therapy by propensity score matching analysis with age as a covariate. Testosterone levels were measured at baseline and after 3-month treatment.ResultsAfter 3-month treatment, the control group had higher levels of total testosterone, free and bioavailable testosterone than those at baseline (P<0.05). Compared with the control group, the change of total (-0.82 ± 0.59 vs. 0.99 ± 0.59 nmol/L) and bioavailable (-0.13 ± 0.16 vs. 0.36 ± 0.16 nmol/L) testosterone levels in the metformin group significantly decreased (P=0.036 and 0.029, respectively). In Glycated Albumin (GA) improved subgroup, the TT, FT, and Bio-T levels in the control subgroup were higher than their baseline levels (P < 0.05). Compared with the metformin subgroup, TT level in the control subgroup also increased significantly (P=0.044). In GA unimproved subgroup, the change of TT level in the metformin subgroup was significantly lower than that in the control subgroup (P=0.040).ConclusionIn men with T2DM, 3-month metformin therapy can reduce testosterone levels, and counteract the testosterone elevation that accompanied with the improvement of blood glucose.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT04847219?term=04847219&draw=2&rank=1.

Intensive Medical Nutrition Therapy Alone or with Added Metformin to Prevent Gestational Diabetes Mellitus among High-Risk Mexican Women: A Randomized Clinical Trial

The aim of this study was to examine the efficacy of intensive medical nutrition therapy (MNT) plus metformin in preventing gestational diabetes mellitus (GDM) among high-risk Mexican women. An open-label randomized clinical trial was conducted. Inclusion criteria were pregnant women with three or more GDM risk factors: Latino ethnic group, maternal age >35 years, body mass index >25 kg/m2, insulin resistance, and a history of previous GDM, prediabetes, a macrosomic neonate, polycystic ovarian syndrome, or a first-degree relative with type 2 diabetes. Women before 15 weeks of gestation were assigned to group 1 (n = 45): intensive MNT-plus metformin (850 mg twice/day) or group 2 (n = 45): intensive MNT without metformin. Intensive MNT included individual dietary counseling, with ≤50% of total energy from high carbohydrates. The primary outcome was the GDM incidence according to the International Association of Diabetes Pregnancy Study Groups criteria. There were no significant differences in baseline characteristics and adverse perinatal outcomes between the groups. The GDM incidence was n = 11 (24.4%) in the MNT plus metformin group versus n = 7 (15.5%) in the MNT without metformin group: p = 0.42 (RR: 1.57 [95% CI: 0.67–3.68]). There is no benefit in adding metformin to intensive MNT to prevent GDM among high-risk Mexican women. Clinical trials registration: NCT01675310.

Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients

Purpose We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic. Patients and Methods Seventy-eight non-diabetic patients were randomly selected and beinaglutide or metformin was administered for 12 weeks. The primary endpoints were changes in body weight and the proportions of patients who lost≥5 and≥10% of their baseline body weights. Results A total of 64 patients completed the study; patients in the beinaglutide group exhibited more bodyweight loss than those in the metformin group [(9.5±0.8%; 9.1±0.9 kg) and (5.1±0.9%; 4.5±0.8 kg), respectively, corresponding to a difference of approximately 4.5 kg (95% confidence interval, 2.2–6.9 kg; P<0.01)]. In the beinaglutide group, 90.6 and 40.6% of the patients lost≥5 and≥10% of their body weight, respectively, whereas, in the metformin group, these rates were 46.9 and 12.5%, respectively (P<0.01 and P<0.05). Weight loss following beinaglutide treatment mainly resulted from the loss of fat mass. Compared to metformin, beinaglutide induced a greater decrease in the body mass index, weight circumference, percent body fat, and body fat mass (total, trunk, limb, android, and gynoid). Additionally, beinaglutide decreased serum insulin levels and ameliorated insulin resistance. Conclusions Beinaglutide is more efficient than metformin at reducing weight and fat mass in patients who are overweight/obese and non-diabetic. Beinaglutide may be a useful therapeutic option for overweight/obesity control in the Chinese population.

Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People’s Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

To Compare Metformin Vs Insulin in Gestational Diabetes in Terms of Neonatal Hypoglycemia

Aim: To compare metformin vs insulin in Gestational Diabetes in terms of neonatal hypoglycemia. Methodology: Study design: Randomized controlled trial Setting: Obstetrics / Gynecology Unit-l, Holy Family Hospital, Rawalpindi. Duration of study: 6 months i.e. 10-11-2017 to 10-05-2018 Data collection procedure: 240 patients were randomly allotted into two groups; A & B. Group A received metformin and group B received regular insulin. Patient was admitted at 36 wks onwards. Neonatal hypoglycemia was measured and entered in structured Performa. All the data was entered and analyzed through SPSS version 22. Results: In this study, the mean ± sd ages of patients were 28.7±5.05 years in insulin group while 28.01±4.37years in metformin group. Mean neonatal blood sugar level was 51.58±11.77mg/dl in insulin group while 57.37±10.61mg/dl in metformin group. The difference was significant (p<0.05). In this study, neonatal hypoglycemia was noted in 28 (23.3%) cases with insulin while in 1 (0.8%) case with metformin. The difference was significant (p<0.05). Conclusion: Metformin has better outcome than insulin in terms of less number of neonatal hypoglycemia. Key words: Gestational Diabetes, Metformin, Insulin, Neonatal Hypoglycemia

Metformin on Insulin, Glucagon, Oxidative Stress Markers and Pancreatic Tissue Histology in Streptozotocin-Induced Diabetic Rats

This study determined the effects of Metformin on plasma insulin, glucagon, oxidative stress status and histology of pancreas in diabetic rats. Grouping was carried out on 21 rats, and were assigned into 3 groups (n = 7 rats per group); non-DM, DM and DM+metformin (200 mg/kg). Diabetes Mellitus was induced and treatments were given daily by oral gavage for 4 weeks. Food intake, fasting blood glucose (FBG), glucagon, malondialdehyde and protein carbonyl were significantly higher while final body weight, insulin and total antioxidant capacity were significantly lower in Diabetes Mellitus group compared with non- Diabetes Mellitus group. There was significantly higher body weight, insulin level and total antioxidant capacity with significantly lower food intake, FBG, glucagon, malondialdehyde and protein carbonyl levels in Diabetes Mellitus +Metformin group compared with the Diabetes Mellitus group. Pancreatic tissue histology revealed islet cells regeneration in Diabetes Mellitus +Metformin group. This in vivo study provides evidence of the potential of antihyperglycemic and improved oxidants- antioxidant status which may be due to the oral hypoglycaemic nature or effects of metformin as seen in this study.

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis

Aims We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). Methods We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. Results A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) − 0.07; 95%CI − 0.11, − 0.02) and preeclampsia (RD − 0.03; 95%CI − 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD − 0.17; 95%CI − 0.25, − 0.08) and maternal weight gain (SMD − 0.61; 95%CI − 0.86,− 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. Conclusions The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Metformin Exerts An Antitumor Effect By Inhibiting Bladder Cancer Cell Migration And Growth, And Promoting Apoptosis Through The PI3K/AKT/mTOR Pathway

Background To observe and explore the effect of metformin on the migration,and proliferation of bladder cancer T24 and 5637 cells in vitro.Methods Bladder cancer T24 and 5637 cell lines were cultured in vitro, and were divided into group A (blank control group) and group B (metformin group: 5, 10, 15, and 20 mmol/L); both groups were plated on 6-well plates at the same time. Culture in 24-well plates was used for wound healing assays and in 96-well plates for Transwell migration and invasion, and Cell Counting Kit-8 proliferation experiments. We observed and detected the cell migration and proliferation ability of each group at 48 hours, and calculated the cell migration area and survival rate. Flow cytometry was used to detect cell apoptosis in the groups. The apoptosis-related protein, cleaved-caspase 3, cleaved-PARP and PI3K/AKT/mTOR signaling pathway member proteins PI3K, phosphorylated (p)-PI3K, AKT, p-AKT, mTOR, and p‑mTOR were detected using western blotting.Results After 48 hours of treatment with different concentrations of metformin, the cell migration and proliferation capabilities were significantly lower than those in the blank control group. The proliferation and migration abilities of T24 and 5637 cells decreased in a metformin concentration-dependent manner (P < 0.05). The apoptosis rate under different concentrations of metformin, as detected by flow cytometry, showed a significantly higher rate in the metformin group than in the control group (P＜0.05). Compared with that in the control group, the level of cleaved‑caspase 3 and cleaved-parp protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05).Conclusion Metformin inhibit bladder cancer T24 and 5637 cell migration and proliferation, and induced their apoptosis. The mechanism might involve inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.

Efficacy and Safety of Metformin Use in Rheumatoid Arthritis: A Randomized Controlled Study

Objective: To evaluate the efficacy and safety of metformin use in rheumatoid arthritis (RA) patients receiving conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs).Methods: A prospective, randomized, controlled, single blinded, study was carried on 66 RA patients with moderate and high disease activity state, receiving csDMARDs. Patients were simply randomized to receive either metformin 850 mg twice daily (Metformin group, n = 33), or placebo twice daily (Control group, n = 33) in addition to their stable anti-rheumatic regimen and followed up for 6 months. Serum C-reactive protein (CRP), disease activity of 28 joints based on CRP (DAS-28-CRP), and quality of life (QOL) were evaluated at baseline and then every 3 months. Moreover, serum adiponectin was assessed at baseline and after 6 months.Results: Sixty patients completed the study. Drop out was due to intolerance to metformin side effects (n = 3) and non-compliance (n = 3). Metformin significantly decreased CRP levels and DAS-28-CRP after 6 months compared to the control group (p-value &lt;0.001). A significant improvement in QOL of metformin group was observed as early as after 3 months (p-value = 0.006) with a continued improvement observed at 6 months (p-value &lt;0.001) compared to the control group. Despite the significantly higher serum adiponectin in the metformin group at baseline, it was significantly reduced after 6 months in the metformin group with median percent change of −63.49% compared to the significant increase in the control group with median percent change of 92.40%.Conclusion: Metformin significantly improved inflammation, disease severity, and QOL in RA patients with high safety profile.Clinical Trial Registration: Clinical-Trials.gov, identifier [NCT08363405].

Effects of crocin and metformin on methylglyoxal-induced reproductive system dysfunction in diabetic male mice

Objective: This study investigated the effect of crocin in methylglyoxal (MGO)-induced diabetic male mice.Methods: Seventy 1-month-old male NMRI mice weighing 20–25 g were divided into seven groups (n=10): sham, MGO (600 mg/kg/day), MGO+crocin (15, 30, and 60 mg/kg/day), MGO+metformin (150 mg/kg/day), and crocin (60 mg/kg/day). MGO was administered orally for 30 days. Starting on day 14, after confirming hyperglycemia, metformin and crocin were administered orally. On day 31, plasma and tissue samples were prepared for experimental assessments. Results: Blood glucose and insulin levels in the MGO group were higher than those in the sham group (p<0.001), and decreased in response to metformin (p<0.001) and crocin treatment (not at all doses). Testis width and volume decreased in the MGO mice and improved in the crocin-treated mice (p<0.05), but not in the metformin group. Superoxide dismutase levels decreased in diabetic mice (p<0.05) and malondialdehyde levels increased (p<0.001). Crocin and metformin improved malondialdehyde and superoxide dismutase. Testosterone (p<0.001) and sperm count (p<0.05) decreased in the diabetic mice, and treatment with metformin and crocin recovered these variables. Luteinizing hormone levels increased in diabetic mice (p<0.001) and crocin treatment (but not metformin) attenuated this increase. Seminiferous diameter and height decreased in the diabetic mice and increased in the treatment groups. Vacuoles and ruptures were seen in diabetic testicular tissue, and crocin improved testicular morphology (p<0.01). Conclusion: MGO increased oxidative stress, reduced sex hormones, and induced histological problems in male reproductive organs. Crocin and metformin improved the reproductive damage caused by MGO-induced diabetes.