Clinical Efficacy Of Metformin Research Articles

Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora.

Metformin has been reported to inhibit the occurrence and development of colorectal cancer (CRC) by mediating changes in intestinal flora. Studies have also indicated that the occurence of familial adenomatous polyposis (FAP) may also be associated with changes in the intestinal flora. Therefore, we investigated the efficacy and safety of metformin in treating FAP and the association with intestinal flora. Compared with the baseline, the mean number and load of polyps in the areas of nanocarbon labeling and postoperative residuals in the test group were lower than those in the placebo group, while the diversity of intestinal flora species was increased. At the genus level, the relative abundance of g_Ruminococcus in the test group was lower than that at baseline, whereas the relative abundance of g_Lactobacillus was higher. These changes were statistically significant (P < 0.05). One-year metformin therapy for FAP is safe and effective, potentially mediated by modulating the intestinal flora. This study provides new insights and strategies for preventing adenomatous polyp carcinogenesis in FAP and explores possible preventive action.

P76.07 Metformin Enhances the Efficacy of EGFR-TKIs in Advanced Non-Small Cell Lung Cancer Patients With Type 2 Diabetes Mellitus

Lung cancer remains the leading cause of cancer-related mortality around the world. Despite epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) therapy have shown remarkable clinical efficacy in non-small cell lung cancer (NSCLC) patients, resistance is almost inevitable and is still a major obstacle. Studies have suggested that the prolonged use of metformin, a common oral anti-diabetes agent, also an IGF-1R inhibitor, is associated with survival benefits among NSCLC Type 2 diabetes mellitus (T2DM) patients. However, the clinical efficacy of metformin and EGFR-TKIs in combination, especially third-generation TKIs, on NSCLC patients with T790M mutation has not been well validated. Therefore, we retrospectively reviewed the effect of metformin use on the clinical efficacy of EGFR-TKIs in NSCLC patients with T2DM, and we also carried out in vitro experiment to demonstrate the effects of metformin in EGFR-TKI resistant cell lines in aspect of proliferation and apoptosis. We retrospectively reviewed clinicopathological characteristics and response of NSCLC patients with type 2 diabetes mellitus (T2DM) who received EGFR-TKIs treatment. Therapeutic outcome including objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) of first-line EGFR-TKIs and second-line osimertinib were compare between patients received metformin and other anti-diabetes drugs. In addition, the effect of metformin on gefitinib-resistant cell line PC9R and osimertinib-resistant cell line PC9R/OR was examined in vitro using Cell Counting Kit-8, and apoptosis analysis, the IC50, apoptosis rate and combination index (CI) was calculated. In fist-line EGFR-TKIs treatment, ORR in metformin use group was significantly higher (85.7% vs. 47.4%, p=0.001). The PFS1 and OS1 in metformin use group were significantly longer (21.6 months vs. 9.2 months, p =0.000; 48.4 months vs. 36.6 months, p =0.049). Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs with T790M. In vitro analysis, metformin showed synergistic interaction both with gefitinib in PC9R (CI=0.77) and with osimertinib in PC9R/OR (CI=0.77) in proliferation inhibition analysis. Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs in vitro (p<0.05). The results of our study suggest metformin use could be beneficial to NSCLC patients with T2DM treated with either first-line EGFR-TKIs or second-line osimertinib treatment.

Effect of metformin combined with telmisartan on blood pressure and insulin in obese hypertensive patients with impaired glucose tolerance

Objective To investigate the clinical efficacy of metformin combined with telmisartan in obese hypertensive patients with impaired glucose tolerance, and to observe the effect of metformin combined with telmisartan on blood pressure and insulin. Methods 92 patients of obese hypertensive with impaired glucose tolerance were included in this study, they were randomly divided into two groups according to the digital table, 46 cases in each group.The two groups of patients were given symptomatic treatment, on this basis, the control group was given telmisartan, the observation group was given telmisartan and metformin tablets.The blood glucose levels, fasting insulin, 2 h postprandial insulin and body mass index were measured before treatment and after treatment for 12 weeks.The insulin sensitivity index (ISI) and insulin resistance index (HOMA-IS) were measured 12 weeks after treatment.The clinical antihypertensive effect and adverse reactions were analyzed. Results After treatment for 12 weeks, the levels of fasting blood glucose, and 2h postprandial glucose, fasting insulin, 2h postprandial insulin and body mass index of the observation group were (5.11±0.38)mmol/L, (7.12±0.75)mmol/L, (22.47±4.26)mmol/L, (161.25±41.75)mU/L, (25.78±2.11)kg/m2, respectively, which in the control group were (5.59±0.41)mmol/L, (8.36±0.71)mmol/L, (26.75±4.17)mU/L, (179.88±42.65)mU/L, (27.69±2.28)kg/m2, respectively, the differences were statistically significant (t=5.82, 8.14, 4.86, 2.11, 4.17, P=0.00, 0.00, 0.00, 0.03, 0.00). After treatment for 12 weeks, the ISI and HOMA-IS of the observation group were (-2.79±0.38), (3.07±1.02), respectively, which of the control group were (-3.15±0.47), (3.65±1.25), respectively, the differences were statistically significant (t=4.03, 2.43, P=0.00, 0.01). The indicators of the two groups were significantly improved compared with before treatment (P<0.05). The total effective rate of the observation group was 76.09%, which was significantly higher than 41.30% of the control group (χ2=11.57, P=0.00). There was no serious adverse reaction during the treatment period. Conclusion Metformin combined with telmisartan in the treatment of obese hypertensive patients with impaired glucose tolerance can help to improve the body mass index, blood pressure, blood glucose, insulin and other indicators, and has certain safety. Key words: Metformin; Telmisartan; Obesity; Hypertension; Impaired glucose tolerance

Prospects of metformin in the treatment of endometriosis

According to recent year studies, the classical biguanide metformin has antiproliferative, proapoptotic and anti-inflammatory effects in addition to the main hypoglycemic effect. There are clinical and experimental studies these effects in the therapy of oncological and benign hyperplastic diseases. There is no data about the clinical efficacy of metformin in the therapy of endometriosis in the domestic literature, and there were a few studies in foreign sources. There was a decrease in the severity of the pain syndrome and an increase of pregnancy rate in two clinical studies with small samples. However, future studies are needed to investigate the mechanisms of the target drug effect and to develop effective regimens for the treatment of endometriosis.

Abstract CT075: Tumor mutation status will predict metabolic response to metformin in lung cancer treated with stereotactic body radiation therapy (SBRT)

Abstract At present, there are over 100 clinical trials examining the role of metformin in malignancy, either alone or in combination with chemotherapy. However, despite significant preclinical data, trials examining the role of metformin as a radiosensitizer are few. Moreover, the effects of endogenous tumor mutations on response to metformin are unknown, as some data suggests that certain mutations (eg. TP53, STK11) may confer sensitivity to this agent. Finally, the effects of metformin on FDG-uptake in solid tumors is far from clear, as this agent can actually lead to an increased uptake of FDG in normal bowel. Because of these questions, we have designed an imagining-guided trial of 70 patients, randomized 6:1 in favor of metformin treatment in patients with non-small cell lung cancer to be treated with stereotactic body radiotherapy (SBRT). Patients receive either placebo or metformin at a loading dose of 1,000 mg per day for one week followed by 1-2 weeks of metformin at 2,000 mg per day. Prior to study entry, an FDG-PET scan is performed which is then repeated after 2-3 weeks of metformin treatment. Metformin or placebo is maintained throughout SBRT and the standard daily cone-beam CTs are taken. Metformin or placebo stops at the end of SBRT followed by an additional FDG-PET scan 6 months after completion of therapy. All tumors with available tissue will be subjected to targeted sequencing. The primary outcome is FDG-PET response following initial metformin or placebo monotherapy as well as at 6 months. Secondary outcomes include the effect of common mutations (TP53, STK11, Kras) on metformin FDG-PET response. Currently, 14 patients have been registered for this trial. We anticipate that this study will provide a unique insight on how metformin affects FDG-PET response, if this response is affected by tumor mutation status, and provide preliminary data on the clinical efficacy of metformin in the setting of SBRT. Citation Format: Heath D. Skinner, Thomas Guerrero, Brian Hobbs, Laurence Court, Paige L. Nitsch, John Heymach. Tumor mutation status will predict metabolic response to metformin in lung cancer treated with stereotactic body radiation therapy (SBRT). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT075.

Inter-patient Variability in Clinical Efficacy of Metformin in Type 2 Diabetes Mellitus Patients in West Bengal, India

Background and objective: Metformin is often used as a first-line therapy for Type 2 diabetes mellitus (T2DM), but the glycemic response to metformin is variable in patients. Here, we aimed to assess the inter-patient variability in terms of glycemic response to metformin in the state of West Bengal, India. Material and methods: We enrolled newly diagnosed treatment naive 113 patients with T2DM. Patients were subjected to assay of glycated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PP) and measurement of body mass index (BMI), waist circumstances (WC) before and after the end of 3 months of immediate release metformin (2000mg/day) therapy. Results: Out of 113 patients, 111 (58 male and 53 female; average age 43.13 years) were provided with 3 months of metformin therapy. 102 individuals responded to metformin, but HbA1c levels of 9 patients did not improve after 3 months of drug therapy. Conclusions: In the present study, metformin lead to improvements in glycemic control in 92% of newly diagnosed T2DM patients but in 8% does not which is much less in this part of India.

Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Previous studies have demonstrated this in other populations with conflicting results, but it remains to be elucidated in Indian population. Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. A total of 122 newly detected, treatment naive T2DM patients of either sex were included in this study. The patients were started on metformin monotherapy and followed up for 12 weeks. Genotype was determined using qRT-PCR. Before and after treatment with metformin, body mass index (BMI), serum lipid profile, glycated hemoglobin (HbA1c), fasting and postprandial glucose level, and blood pressure (BP) were measured. The study cohort mean age was 49.57 ± 9.88 years. Of the 122 T2DM patients, 93 were classified as responders and 29 as non-responders based on fall in HbA1c levels. Interestingly, carriers of one variant allele 'C' (AC) of rs622342 polymorphism were less among the responders than those who did not (44.8 vs. 22.6 %). The response was even lesser (13.8 vs. 4.3 %) in carriers of two copies of "C" allele (CC). On the contrary, patients with two copies of allele 'A' (AA) had 5.6 times greater chance of responding to metformin treatment. A similar trend was observed when the proportion was analyzed under different genetic models (OR 3.85, 95 % CI 1.61-9.19 for dominant; OR 3.56, 95 % CI 0.83-15.26 for recessive; OR 0.35, 95 % CI 0.14-0.86 for over-dominant; and OR 4.10, 95 % CI 1.78-9.43 for additive). Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG, PPG, lipid parameters and BP. These data suggest that the allele and genotypes of SLC22A1 rs622342 gene polymorphism were associated with the therapeutic efficacy of metformin in South Indian patients with T2DM.

Metformin and Cancer in Type 2 Diabetes

Metformin and Cancer in Type 2 Diabetes

The clinical efficacy of metformin combined with clomiphene citrate in the treatment of polycystic ovary syndrome

Objective To observe the clinical efficacy of metformin combined with clomiphene citrate in the treatment of polycystic ovary syndrome ( POS ).Methods 104 women with POS and who received routine therapies for induction of ovulation were randomly assigned to receive combination therapy with metformin combined with clomiphene ( 52 women,study group ),or metformin alone ( 52 women,control group ).Bilateral ovarian volume,changes in blood glucose,and levels of fasting insulin,follicle-stimulating hormone,luteinizing hormone,and testosterone levels were compared between the two groups before and after treatment.Results Ovarian volume was lessened at certain degree in both groups after treatment.Levels of BMI,fasting insulin,LH,and testosterone were reduced.Conclusions Metformin combined with clomiphene for polycystic ovary syndrome can effectively lower levels of BMI and hormone,improve endocrine status,and induce ovulation.It is an effective choice for treating this disorder. Key words: Metformin; Clomiphene; Polycystic ovary syndrome; Infertility

Does bitter melon contain an activator of AMP-activated kinase?

Extracts of the unripe fruit of Momordica charantia – bitter melon, which flourishes throughout the tropics – appear to have utility in the management of type 2 diabetes. Rodent studies suggest that the thus-far-uncharacterized active components of such extracts enhance the efficiency of postprandial glucose storage in muscle and liver, and likely diminish excessive hepatic glucose output, while often down-regulating serum insulin – effects comparable to those reported for metformin. Other parallels between the actions of metformin and bitter melon in rodents appear to include: analogous effects on the hepatic activity of certain enzymes of glucose metabolism; increased expression of GLUT4 in the plasma membrane of skeletal muscle; a tendency to prevent weight gain; favorable effects on serum lipids; and an anti-promotional impact on cancer induction. Inasmuch as the clinical efficacy of metformin has recently been traced to its ability to activate AMP-activated kinase, it would be of interest to determine whether bitter melon extracts contain activators of this enzyme. The fact that bitter melon has the potential to down-regulate insulin suggests that, beyond its likely utility in the management of diabetes, it may have preventive value with respect to a wide range of disorders in which hyperinsulinemia plays a pathogenic role – and possibly could even favorably impact the aging process.

Clinical efficacy of metformin against insulin resistance parameters: sinking the iceberg.

It has been increasingly recognised in recent years that type 2 (non-insulin-dependent) diabetes is part of a cluster of cardiovascular risk factors known as the metabolic syndrome, but also endorsed with such names as the deadly quartet, syndrome X and the insulin resistance syndrome. Atherosclerosis is the most common complication of type 2 diabetes among Europeans, and coronary artery, cerebrovascular and peripheral vascular disease are 2 to 5 times more common in people with this condition than in those without diabetes. These observations indicate that the treatment of type 2 diabetes requires agents that do more than simply lower blood glucose levels, and a therapy with both antihyperglycaemic effects and beneficial effects on dyslipidaemia, hypertension, obesity, hyperinsulinaemia and insulin resistance is likely to be most useful. In this respect, metformin has an important and established role: this drug has been shown to lower blood glucose and triglyceride levels, and to assist with weight reduction and to reduce hyperinsulinaemia and insulin resistance. Studies in the Israeli sand rat, Psammomys obesus, have indicated hyperinsulinaemia/insulin resistance to be the initial and underlying metabolic disorder in obesity and type 2 diabetes. Thus, the well established effect of metformin in reducing insulin resistance makes this drug an excellent candidate for the prevention of progression of impaired glucose tolerance to type 2 diabetes, and for the reduction of mortality associated with cardiovascular disease.