• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.243-249
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• 2018

Background: The new type of diabetes treatment, SGLT2 inhibitors, has been approved for monotherapy and combination therapy, but medical insurance is only allowed in combination therapy with metformin, which is the first choice for type 2 diabetes treatment. Methods: The SGLT2 inhibitors prescribed in Korea are dapagliflozin, empagliflozin and ipragliflozin. A review was conducted using Pubmed to evaluate efficacy and safety for these medications with metformin combination therapy. 10 studies were selected by searching for keywords and related references and were reviewed in full. The mechanism of action, pharmacokinetics, and the economics of treatment with SGLT2 inhibitors were examined. Results: SGLT2 inhibitors had moderate glycemic control when added to the treatment of patients with type 2 diabetes who were not being regulated by metformin monotherapy. They also showed positive effects such as weight loss, as well as the lowering of blood pressure. Hypotension and serious side effects were relatively low. However, the risk of genital infection was increased. Conclusion: The SGLT2 inhibitors are a new class of drugs that promote glucose excretion in the urine. They are a good choice for combination therapy with metformin for the treatment of type 2 diabetes, with weight loss and very low risk of serious side effects.

• Tuberculosis and Respiratory Diseases
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• v.80 no.3
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• pp.296-303
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• 2017

Background: Acute respiratory distress syndrome (ARDS) is related to high mortality and morbidity. There are no proven therapeutic measures however, to improve the clinical course of ARDS, except using low tidal volume ventilation. Metformin is known to have pleiotropic effects including anti-inflammatory activity. We hypothesized that pre-admission metformin might alter the progress of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM). Methods: We performed a retrospective cohort study from January 1, 2005, to April 30, 2005 of patients who were admitted to the medical ICU at Seoul National University Hospital because of ARDS, and reviewed ARDS patients with DM. Metformin use was defined as prescribed within 3-month pre-admission. Results: Of 558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33 patients were treated with metformin monotherapy or in combination with other antidiabetic medications. Demographic characteristics, cause of ARDS, and comorbid conditions (except chronic kidney disease) were not different between metformin users and nonusers. Several severity indexes of ARDS were similar in both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in metformin nonusers. On multivariable regression analysis, use of metformin was not significantly related to a reduced 30-day mortality (adjusted ${\beta}-coefficient$, -0.19; 95% confidence interval, -1.76 to 1.39; p=0.816). Propensity score-matched analyses showed similar results. Conclusion: Pre-admission metformin use was not associated with reduced 30-day mortality among ARDS patients with DM in our medical ICU.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.123-132
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• 2013

Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, $PGE_2$ and pro-inflammatory cytokines ($IL-1{\beta}$, IL-6 and $TNF-{\alpha}$) through down-regulation of $NF-{\kappa}B$ translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of $TNF-{\alpha}$ and reduced the protein and mRNA expression of $TNF-{\alpha}$ in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of $TNF-{\alpha}$ and the expressions of scavenger receptors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.595-600
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• 2015

Background: Accumulating evidence suggests that metformin possesses anticarcinogenic properties, and its use is associated with favorable outcomes in several cancers. However, it remains unclear whether metformin influences prognosis in prostate cancer (PCa) with concurrent type 2 diabetes (T2D). Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library from database inception to April 16, 2014 without language restrictions to identify studies investigating the effect of metformin treatment on outcomes of PCa with concurrent T2D. We conducted a meta-analysis to quantify the risk of recurrence, progression, cancer-specific mortality, and all-cause mortality. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Publication bias was assessed by Begg's rank correlation test. Results: A total of eight studies fulfilled the eligibility criteria. We found that diabetic PCa patients who did not use metformin were at increased risk of cancer recurrence (RR, 1.20; 95%CI, 1.00-1.44), compared with those who used metformin. A similar trend was observed for other outcomes, but their relationships did not reach statistical significance. Funnel plot asymmetry was not observed among studies reporting recurrence (p=0.086). Conclusions: Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D. Well-designed large studies and collaborative basic research are warranted.

• Journal of Korean Medicine for Obesity Research
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• v.17 no.1
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• pp.20-28
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• 2017

Objectives: The purpose of this study was to investigate anti-obesity effect of Scutellariae Radix extract combined with metformin. Methods: Male C57BL/6 mice, 4 weeks of age, were used to set high-fat diet induced obesity model. They were grouped NOR (normal control), HFD (high fat diet control), MET (metformin, 100 mg/kg/day), MH2 (metformin 50 mg/kg/day+Scutellariae Radix 200 mg/kg/day), and HG4 (Scutellariae Radix 400 mg/kg/day). MET, MH2, and HG4 were orally administered for 10 weeks. Body weight was measured every week. Fasting blood glucose, triglyceride, total cholesterol (TC), high density lipoprotein, glutamic oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) were measured before sacrifice. Oral glucose tolerance test (OGTT) was also performed. Organ weight and internal fat weight were measured after sacrifice. Results: MH2 group showed a reduction of body weight when compared with HFD group. MH2 group showed stable blood level control which was calculated areas under the curves by OGTT. TC, GOT, GPT level, internal fat, and organ weight in MH2 group reduced. Conclusions: The combined treatment of Scutellariae Radix and Metformin has impact on treating obesity. Further studies are needed to evaluate the effect of Metformin and herbal medicine combination therapy.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.204-215
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• 2018

Background: In this systematic review and meta-analysis, the effect of metformin on weight loss was assessed to determine whether metformin should be recommended for the prevention or treatment of weight gain in patients receiving antipsychotic medication for the treatment of schizophrenia or schizoaffective disorder. Methods: The PubMed, Embase, and Cochrane Library databases were searched for all published randomized controlled trials (RCTs) from inception to June 2018. In addition, the references of relevant articles were also examined. Using Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the changes in body weight and body mass index (BMI) and the corresponding 95 % confidence intervals (CIs) were calculated. Results: The meta-analysis included 15 RCTs. The pooled analysis showed that compared with placebo, metformin led to significant reductions in body weight (WMD: -2.09, 95% CI: -2.59, -1.60; p<0.00001) and BMI (WMD: -0.90, 95% CI: -1.08, -0.72; p<0.00001). The effect of metformin on weight loss was greater in patients receiving olanzapine than in patients receiving clozapine (body weight, WMD: -2.39, 95% CI: -3.76, -1.02; p=0.0006 for olanzapine; -1.99, 95% C: -3.47, -0.51; p=0.009 for clozapine; BMI, WMD: -1.15, 95% CI: -1.74, -0.57, p=0.0001 for olanzapine; WMD: 0.76, 95% CI: -1.23, -0.28; p=0.002 for clozapine). Conclusion: Metformin can be recommended to manage olanzapine-induced weight gain in patients with schizophrenia or schizoaffective disorder. The magnitude of the reductionss in body weight and BMI implieds that the use of metformin to attenuate olanzapine-induced weight gain can minimize the risk of coronary heart disease.

• Journal of Nutrition and Health
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• v.32 no.3
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• pp.230-238
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• 1999

The present study was conducted to investigate te effect of sea tangle and hypoglycemic agent(Metformin) on lipid peroxidation and antioxidants levels in normal and diabetic rats. Male Sprague-Dawley rats were fed AIN-76 based experimental diets containing 5% (w/w) cellulose or 15%(w/w) sea tangle for 3 weeks, and then rats of diabetic groups were rendered diabetic by intramuscular injection of streptozotocin(STZ, 45mg/kg BW). After induction of diabetes Metformin(350mg/kg BW) was given once a day using a feeding tube for 5 days. Blood glucose level in diabetic rats fed sea tangle was significantly lower than that of diabetic rats fed cellulose. Metformin feeding resulted in further lowering blood glucose. Plasma and liver microsomal levels of lipid peroxides were increased significantly in diabetic rats as compared to normal rats, and the plasma level tended to be decreased by sea tangle feeding. Plasma level of retinol was reduced by STZ treatment, but it was increased by Metformin feeding in diabetic rats fed sea tangle. The liver contents of retinyl plamitate were reduced in diabetic rats but recovered by sea tangle feeding to some extent. Liver contents of total vitamin A were increased significantly by sea tangle in diabetic rats. Although difference in either plasma or liver level of $\alpha$-tocopherol by diet and STZ treatment was not significant, $\alpha$-tocopherol levels were the highest in the group with simultaneous feeding of sea tangle and metformin. Liver contents of zinc and copper were not influenced by either STZ treatment or sea tangle feeding. The present study indicates that the lowering blood glucose level could be attained by simultaneous trial of sea tangle diet and hypoglycemic agent and the increased oxidative stress caused by STZz treatment could be relieved by sea tangle feeding.

• Biomedical Science Letters
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• v.23 no.3
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• pp.290-294
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• 2017

Metformin or sodium salicylate is known to induce apoptosis and G0/G1 phase arrest in a variety of cancer cells. However, the anti-cancer effects of the combined treatments for these drugs-induced apoptosis are yet unclear. Here, we found that the combined treatment of metformin and sodium salicylate increased the efficacy of chemotherapeutics against breast cancer cells. These combined drugs significantly inhibited cellular proliferation and induced apoptosis at an earlier stage in human MCF-7 breast cancer cells. Also, co-treatments of metformin and sodium salicylate induced G1 cell cycle arrest in MCF-7 cells more effectively than either agent alone. Taken together, these results demonstrate that dual metformin/sodium salicylate treatment prevents proliferation of MCF-7 cells by inducing apoptosis and G1 cell cycle arrest.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.221-225
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• 2015

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether it can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.50-54
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• 2010

Purpose: The uptake of $^{18}F$-FDG is often observed in normal cell of colon to patients who have non-insulin-dependent diabetes mellitus and had taken anti-diabetic drugs including Metformin in PET/CT scan. In this study, the region of colon was compared between the patients who took anti-diabetic drugs including Metfomin and other patients who took the other anti-diabetic drugs through SUV measurements. Materials and Methods: A hundred eighty patients were studied. 120 patients who have non-insulin-dependent diabetes mellitus (Including Metformin: 60, Excluding Metformin: 60) and 60 patients as a control group were composed. The patient fasted at least 6 hours before receiving an intravenous injection of 370-592 MBq (10-16 mCi) of $^{18}F$-FDG. Scanning from the base of the skull though the mid thigh was performed using the Discovery STe PET/CT Equipment (GE Healthcare, Milwaukee, WI, USA). The highest uptake region was measured SUV among ascending, transverse and descending colon. Results: The values of patients who took the anti-diabetic drugs including Metformin were $6.16{\pm}3.64$ g/mL, $4.41{\pm}2.94$ g/mL, and $5.46{\pm}2.44$ g/mL. The patients who took the anti-diabetic drugs which does not have Metformin were $3.05{\pm}1.39$ g/mL, $2.08{\pm}0.97$ g/mL and $3.15{\pm}1.85$ g/mL. The control group were $2.02{\pm}0.88$ g/mL, $1.68{\pm}0.87$ g/mL and $2.19{\pm}1.88$ g/mL. Conclusion: The effect of the intake of Metformin was observed from the SUV on region of large bowel in this study. Thus, it could be helpful for the results by identifying the ingredient of anti-diabetic drug before the examination and the possibility of interpretation of false positive will be reduced.