Metformin Therapy for Acne Vulgaris: A Meta-Analysis.

Acne vulgaris is a common disease, which occurs in adolescents as well as adults and has a significant influence on the patient's quality of life (QoL) in every aspect. Due to resistance to standard therapies, it has become necessary to prospect for new treatment strategies. It is important to highlight that the diagnosis and treatment of the underlying cause of acne such as metabolic and hormonal disorders may significantly improve the effectiveness of acne treatment. The correlation between Insulin Resistance (IR) and acne has been proven. Both disorders share many common occurrence factors and activation pathways. Metformin, an antihyperglycemic agent, seems to be a possible therapy option, not only because of its insulin sensitizing ability but also via plenty of additional effects of this medicine. While the efficiency of metformin therapy in patients with acne and Polycystic Ovary Syndrome (PCOS) is well explored, it is still necessary to evaluate it in patients without any endocrinopathies. This meta-analysis aimed to estimate the effectiveness of oral metformin as a monotherapy in acne patients without PCOS or other endocrinopathies. Study selection was performed with included criteria such as no PCOS and other endocrinopathies diagnosed, oral administration of metformin, and metformin in monotherapy. Selected studies contained comparisons in the Global Acne Grading System (GAGS) before and after metformin therapy. Statistical analysis detected significant improvement in skin condition after treatment with metformin.

Metabolic Syndrome and Adipokines Profile in Bipolar Depression.

Metabolic syndrome (MS) is a growing social, economic, and health problem. MS coexists with nearly half of all patients with affective disorders. This study aimed to evaluate the neurobiological parameters (clinical, anthropometric, biochemical, adipokines levels, and ultrasound of carotid arteries) and their relationship with the development of MS in patients with bipolar disorder. The study group consisted of 70 patients (50 women and 20 men) hospitalized due to episodes of depression in the course of bipolar disorders. The Hamilton Depression Rating Scale was used to assess the severity of the depression symptoms in an acute state of illness and after six weeks of treatment. The serum concentration of adipokines was determined using an ELISA method. The main finding of this study is that the following adipokines correlated with MS in the bipolar depression women group: visfatin, S100B, and leptin had a positive correlation, whereas adiponectin, leptin-receptor, and adiponectin/leptin ratio showed a negative correlation. Moreover, the adiponectin/leptin ratio showed moderate to strong negative correlation with insulin level, BMI, waist circumference, triglyceride level, treatment with metformin, and a positive moderate correlation with HDL. The adiponectin/leptin ratio may be an effective tool to assess MS in depressed female bipolar patients.

Real-World Observational Study on Vildagliptin With Insulin (VIL-INS) or Vildagliptin and Metformin With Insulin (VIL-MET-INS) Therapy in Indian Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE:  The therapeutic use of vildagliptin and insulin (VIL-INS) or vildagliptin and metformin in combination with insulin (VIL-MET-INS) in the Indian scenario has yet to be explored by generating real-world evidence. Therefore, the present study aimed to evaluate the demographic, clinical characteristics, and treatment patterns of patients with type 2 diabetes mellitus (T2DM) in Indian settings in the above context. METHODOLOGY:  This observational study conducted at 600 healthcare centers in India retrospectively analyzed data of adult patients with T2DM who had been treated with either vildagliptin with insulin or a combination of vildagliptin and metformin with insulin. Data were collected from medical records and analyzed by appropriate statistical tests. RESULTS:  A total of 12,603 patients with T2DM were included with a mean age of 53.4 years of which 63.8% were males. The majority of patients (n=6511; 51.7%) received a combination of vildagliptin and metformin on top of insulin. A significantly high proportion of patients in the age group of 18-40 years received this treatment compared to patients who were initiated on insulin treatment after vildagliptin and metformin combination (11.6% vs. 9.7%; P<0.001). Of all the patients, 70.0% were able to achieve target glycemic control with either VIS-INS or VIL-MET-INS. After treatment with VIL-INS or VIL-MET-INS, the mean glycated hemoglobin (HbA1c) levels significantly decreased with a mean change of 1.46%. Out of all patients, 13.5% experienced weight changes during treatment, with 67.4% of them showing weight loss. A total of 68 patients reported hypoglycemic events and among them, 49 patients had mild hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a majority of patients rated their experience as good to excellent (86.3% and 86.0%, respectively). CONCLUSION:  Both treatment regimens were effective in terms of reduced HbA1c to achieve glycemic control. Furthermore, it is well tolerated without an increase in the risk of hypoglycemia or weight gain. Hence, this therapy has favorable outcomes for T2DM management in Indian clinical settings.

Effects of Slow-Acting Metformin Treatment on the Hormonal and Morphological Thyroid Profile in Patients with Insulin Resistance.

Metformin appears to reduce TSH levels in untreated hypothyroid patients. In contrast, in euthyroid patients with type 2 diabetes mellitus (T2DM), metformin is initially devoid of effects on TSH. However, it is followed by a significant reduction in TSH level after twelve months of treatment. Additionally, some evidence suggests that metformin may also improve thyroid morphological abnormalities. This study aimed to evaluate the effects of metformin not only on TSH and thyroid hormone values, but also on thyroid volume and nodules. A total of 50 patients (mean age: 36.9 ± 12.8 years) with insulin resistance (homeostatic model assessment (HOMA) index ≥2.5) and with thyroid uninodular disease were recruited for this study. They were prescribed slow-acting metformin at a daily dose of 500 mg for six months. Treatment with metformin in euthyroid patients with uninodular thyroid disease and insulin resistance reduces TSH levels, increases FT4 and FT3 values, and decreases thyroid and nodule volumes. These data suggest that metformin may be an effective drug not only for the treatment of T2DM and metabolic syndrome, but also for thyroid disease.

Delayed metformin treatment improves functional recovery following traumatic brain injury via central AMPK-dependent brain tissue repair.

Accumulating evidence suggests that chronic metformin posttreatment offers potent neuroreparative effects against acute brain injury. However, in previous studies, metformin was not initially administered beyond 24 h postinjury, and the effects of delayed metformin treatment in traumatic brain injury (TBI) and other types of acute brain injury and the related mechanisms are unclear. To test this, male C57BL/6 mice received once daily metformin treatment (20, 50 or 100 mg/kg/d, i.p.) at day 1-14, day 1-2, day 1-10, day 3-10, day 5-12 or day 5-28 after cryogenic TBI (cTBI). The results showed that 100 mg/kg/d metformin administered at day 1-14 postinjury significantly promoted motor functional recovery in the beam walking and gait tests and reduced the infarct volume. Metformin (100 mg/kg/d) administered at day 1-10 or day 3-10 but not day 1-2 or day 5-12 after cTBI significantly improved motor functional outcomes at day 7 and 14, and reduced the infarct volume at day 14. Interestingly, the therapeutic time window was further expanded when the duration of metformin treatment starting at day 5 postinjury was extended to 2 weeks. Furthermore, compared with cTBI, the administration of metformin at day 3-10 or day 5-28 after cTBI significantly elevated the expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and growth associated protein 43 (an axonal regeneration marker) and the number of vascular branch points and decreased the area of glial scar and the number of amoeboid microglia in the peri-infarct area at day 14 or 28 postinjury. The above beneficial effects of metformin were blocked by the intracerebroventricular injection of the AMPK inhibitor compound C (40 µg/mouse/d). Our data provide the first evidence that metformin has a wide therapeutic time window for at least 5 days after cTBI, during which it can improve functional recovery by promoting tissue repair and inhibiting glial scar formation and microglial activation in a central AMPK-dependent manner.

Increased kidney cancer risk in diabetes mellitus patients: a population-based cohort study in Lithuania.

BACKGROUND: Diabetes is associated with increased risk of various cancers but its association with kidney cancer is unclear. The objective of this study was to evaluate the association between T2DM with or without metformin use and the risk of kidney cancer in a population-based national cohort in Lithuania. METHODS: The cohort was composed of diabetic patients identified in the NHIF database during 2000-2012. Cancer cases were identified by record linkage with the national Cancer Registry. Standardized incidence ratios (SIRs) for kidney cancer as a ratio of observed number of cancer cases in diabetic patients to the expected number of cancer cases in the underlying general population were calculated. RESULTS: T2DM patients (11,592) between 2000 and 2012 were identified. Overall, 598 cases of primary kidney cancer were identified versus 393.95 expected yielding an overall SIR of 1.52 (95% CI: 1.40-1.64). Significantly higher risk was found in males and females. Significantly higher risk of kidney cancer was also found in both metformin users and never-users' groups (SIRs 1.45, 95% CI: 1.33-1.60 and 1.78 95% CI: 1.50-2.12, respectively). CONCLUSIONS: The patients with T2DM have higher risk for kidney cancer compared with the general Lithuanian population.

Prognostic value of metformin for non-small cell lung cancer patients with diabetes.

BACKGROUND: The anti-cancer role of metformin has been reported in many different kinds of solid tumors, but how it affects non-small cell lung cancer (NSCLC) is currently elusive. The aim of this study was to investigate the influence of metformin treatment on diabetic NSCLC. METHODS: Two hundred fifty-five patients of diabetic NSCLC receiving therapy in our hospital from 2014 to 2016 were enrolled in our study. The information on clinical diagnosis, pathology, and prognosis as well as the influence of metformin in diabetic NSCLC were collected and assessed. Univariate and multivariate analytical techniques were applied to explore how metformin affect the survival of NSCLC. RESULTS: One hundred fifty of the 255 diabetic NSCLC patients took metformin. The median overall survival time (OST) and disease-free survival time (DFST) were significantly prolonged with metformin treatment compared to without metformin treatment (OST 25.0 vs 11.5 months, p = 0.005; DFST 15.6 vs 8.5 months, p = 0.010). Multivariate analysis indicated that metformin treatment could be used to predict the long-term outcome of diabetic NSCLC independently (HR = 0.588, 95% CI 0.466-0.895, p = 0.035). CONCLUSION: Our study revealed that the metformin could help in improving the final outcome of NSCLC patients with diabetes in the long term and thus could be applied to treat NSCLC.