Metformin Ameliorates Arsenic Trioxide Hepatotoxicity Via Inhibiting Mitochondrial Complex I
Cell Death & Disease volume 8, page e3159 (2017) Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects. In the present study, we demonstrated that metformin protected normal hepatocytes from ATO-induced apoptotic cell death in vitro and in vivo. Gene expression screening revealed that glucose metabolism might be related to the metformin-induced protective effect on ATO-treated AML12 cells. The metformin-promoted or induced glycolysis was not responsible for the protection of AML12 cells from ATO-induced apoptotic cell death. Instead, metformin increased the intracellular NADH/NAD+ ratio by inhibiting mitochondrial respiratory chain complex I, further decreasing the intracellular ROS induced by ATO. Treatment with low glucose or rotenone, a mitochondrial respiratory chain complex I inhibitor, also protected AML12 cells from ATO-induced apoptotic cell death. We show for the first time that metformin protects the hepatocyte from ATO by regulating the mitochondrial function. With its properties of chemoprevention, chemosensitization and the amelioration of liver damage, metformin has great prospects for clinical application other than type 2 diabetes mellitus (T2DM). Arsenic trioxide (As2O3, ATO) has long been used as a therapeutic agent for certain severe diseases including malaria, syphilis, leukemia, tu Continue reading >>
A Rare Outcome Induced By Metformin Intoxication: Severe Lactic Acidosis And Hepatotoxicity
1. Aksay E, Yanturali S, Bayram B, et al. A Rare Side Effect of Metformin: Metformin-Induced Hepatotoxicity. Turk J Med Sci 2007; 37 (3): 173-175. 2. Giuliani E, Albertini G, Vaccari C, Barbieri A. pH 6.68-surviving severe metformin intoxication. Q J Med 2010; 103: 887-890. 3. Sencan A, Adanir T, Atay A, et al. High Anion Gap Metabolic acidosis after Suicide: Metformn ntoxication. Anesthesia Journal 2011; 19 (1): 56-59. 4. Heaney D, Majid A and Junor B. Bicarbonate haemodialysis as a treatment of metformin overdose. Nephrol Dial Transplant 1997; 12: 1046-1047. 5. Perincek G, Edis EC, Guldiken S, Uyanik MS. A Rare Outcome Induced by Metformin Intoxication: Severe Lactic Acidosis and Sudden Cardiac Arrest. Kartal Training and Research Medicine Journal 2009; XX(1): 42-44. 6. Zheng L. Metformin as a Rare Cause of Drug-Induced Liver Injury, a Case Report and Literature Review. Am J Ther 2016; 23(1): e315-e317. 7. Nammour FE1, Fayad NF, Peikin SR. Metformin-induced cholestatic hepatitis. Endocr Pract 2003; 9(4): 307-309. 8. Hashmi T. Probable hepatotoxicity associated with the use of metformin in type 2 diabetes. BMJ Case Rep 2011; 2011. pii: bcr0420114092. 9. Saadi T1, Waterman M, Yassin H, Baruch Y. Metformin-induced mixed hepatocellular and cholestatic hepatic injury: case report and literature review. Int J Gen Med 2013; 6: 703-706. 10. Sirtori CR, Franceschini G, Galli-Kienle M, et al. Disposition of metformin (N,N-dimethylbiguanide) in man. Clin Pharmacol Ther 1978; 24: 683-693. 11. Desilets DJ, Shorr AF, Moran KA, Holtzmuller KC. Cholestatic jaundice associated with the use of metformin. Am J Gastroenterol 2001; 96: 2257-2258. 12. Akinci B, Yener S, Bengi G, Yesil S. Alterations of coagulation in metformin intoxication. Hormones 2008; 7(4): 325-329. 13. Packer CD, Hor Continue reading >>
Metformin, The Liver, And Diabetes
Most people think diabetes comes from pancreas damage, due to autoimmune problems or insulin resistance. But for many people diagnosed “Type 2,” the big problems are in the liver. What are these problems, and what can we do about them? First, some basic physiology you may already know. The liver is one of the most complicated organs in the body, and possibly the least understood. It plays a huge role in handling sugars and starches, making sure our bodies have enough fuel to function. When there’s a lot of sugar in the system, it stores some of the excess in a storage form of carbohydrate called glycogen. When blood sugar levels get low, as in times of hunger or at night, it converts some of the glycogen to glucose and makes it available for the body to use. Easy to say, but how does the liver know what to do and when to do it? Scientists have found a “molecular switch” called CRTC2 that controls this process. When the CRTC2 switch is on, the liver pours sugar into the system. When there’s enough sugar circulating, CRTC2 should be turned off. The turnoff signal is thought to be insulin. This may be an oversimplification, though. According to Salk Institute researchers quoted on RxPG news, “In many patients with type II diabetes, CRTC2 no longer responds to rising insulin levels, and as a result, the liver acts like a sugar factory on overtime, churning out glucose [day and night], even when blood sugar levels are high.” Because of this, the “average” person with Type 2 diabetes has three times the normal rate of glucose production by the liver, according to a Diabetes Care article. Diabetes Self-Management reader Jim Snell brought the whole “leaky liver” phenomenon to my attention. He has frequently posted here about his own struggles with soarin Continue reading >>
Protective Effect Of Metformin On Cardiac And Hepatic Toxicity Induced By Adriamycin In Swiss Albino Mice
Protective Effect of Metformin on Cardiac and Hepatic Toxicity Induced by Adriamycin in Swiss Albino Mice Diabetes Mellitus (DM) is a chronic disease that is characterized by deterioration of glycemic control. The disease is known to be caused by imbalance between Reactive Oxygen Species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to investigate if metformin, a very popular antidiabetic agent can avert the cardiac and hepatic toxicity caused by Adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg kg-1 day-1) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg kg-1), 24 h prior to sacrifice. In each case animals were killed, 24 h after the last treatment, blood sample was collected and plasma was separated for analysis of AST, ALT and CK-MB. Liver and heart from the same animals were excised for analysis of proteins, nucleic acids, MDA and NP-SH. The results obtained revealed that pretreatment with metformin (i) reduced the ADR-induced increase in the concentrations of AST, ALT and CK-MB (ii) protected against the ADR-induced increase of MDA and decrease of DNA and NP-SH in both cardiac and hepatic tissues. These results demonstrate that the treatment with metformin might be useful to protect cardiac and hepatic toxicity. The exact mechanism of action is not known, however; the inhibition of ADR-induced increase of plasma enzymes and MDA and depletion of DNA and NP-SH by m Continue reading >>
Diabetes: How Do I Help Protect My Liver?
If I have diabetes, is there anything special I need to do to take care of my liver? Answers from M. Regina Castro, M.D. You're wise to wonder about steps to protect your liver. Diabetes raises your risk of nonalcoholic fatty liver disease, a condition in which excess fat builds up in your liver even if you drink little or no alcohol. This condition occurs in at least half of those with type 2 diabetes. It isn't clear whether the condition appears more often in people with type 1 diabetes than in the general population because obesity, which is a risk factor, occurs with similar frequency in both groups. Other medical conditions, such as high cholesterol and high blood pressure, also raise your risk of nonalcoholic fatty liver disease. Fatty liver disease itself usually causes no symptoms. But it raises your risk of developing liver inflammation or scarring (cirrhosis). It's also linked to an increased risk of liver cancer, heart disease and kidney disease. Fatty liver disease may even play a role in the development of type 2 diabetes. Once you have both conditions, poorly managed type 2 diabetes can make fatty liver disease worse. Your best defense against fatty liver disease includes these strategies: Work with your health care team to achieve good control of your blood sugar. Lose weight if you need to, and try to maintain a healthy weight. Take steps to reduce high blood pressure. Keep your low-density lipoprotein (LDL, or "bad") cholesterol and triglycerides — a type of blood fat — within recommended limits. Don't drink too much alcohol. If you have diabetes, your doctor may recommend an ultrasound examination of your liver when you're first diagnosed and regular follow-up blood tests to monitor your liver function. Continue reading >>
Metformin
DRUG RECORD Introduction Metformin is a first line agent for the treatment of type 2 diabetes that can be used alone or in combination with sulfonylureas, thiazolidinediones or other hypoglycemic agents. Metformin has not been linked to serum enzyme elevations during therapy and is an exceeding rare cause of idiosyncratic clinically apparent acute liver injury. Background Metformin (met for' min) is a biguanine and acts as an insulin sensitizing agent, probably through activation of adenosine monophosphate dependent (AMP) kinase in liver and muscle tissue. Metformin is often associated with weight loss making it a preferred, first line agent for management of overweight patients with type 2 diabetes. Initial concerns about the possibility that metformin (like the related biguanine phenformin) could induce lactic acidosis have been largely resolved, although the agent is contraindicated in patients with renal dysfunction because of this reason and should be used with caution in patients with significant liver disease. Metformin was approved for use in the United States in 1995 and is currently one of the most commonly used drugs for the therapy of diabetes, with more than 30 million prescriptions filled in the United States yearly. Metformin is available in many generic forms in tablets of 500, 850 or 1000 mg, the recommended regimen being to start with 500 or 850 mg once daily and increase based upon tolerance to 1000 to 2550 mg daily taken in two divided doses. Commercial formulations include Glucophage, Glumetza, Fortamet and Riomet. Metformin is also available in extended release formulations and in combinations with sulfonylureas such as glipizide (Metaglip) or glyburide (Glucovance), DDP-4 inhibitors such as alogliptin (Kazano), linagliptin (Jentadueto), saxaglipti Continue reading >>
Side Effects Of Metformin: What You Should Know
Metformin is a prescription drug used to treat type 2 diabetes. It belongs to a class of medications called biguanides. People with type 2 diabetes have blood sugar (glucose) levels that rise higher than normal. Metformin doesn’t cure diabetes. Instead, it helps lower your blood sugar levels to a safe range. Metformin needs to be taken long-term. This may make you wonder what side effects it can cause. Metformin can cause mild and serious side effects, which are the same in men and women. Here’s what you need to know about these side effects and when you should call your doctor. Find out: Can metformin be used to treat type 1 diabetes? » Metformin causes some common side effects. These can occur when you first start taking metformin, but usually go away over time. Tell your doctor if any of these symptoms are severe or cause a problem for you. The more common side effects of metformin include: heartburn stomach pain nausea or vomiting bloating gas diarrhea constipation weight loss headache unpleasant metallic taste in mouth Lactic acidosis The most serious side effect metformin can cause is lactic acidosis. In fact, metformin has a boxed warning about this risk. A boxed warning is the most severe warning from the Food and Drug Administration (FDA). Lactic acidosis is a rare but serious problem that can occur due to a buildup of metformin in your body. It’s a medical emergency that must be treated right away in the hospital. See Precautions for factors that raise your risk of lactic acidosis. Call your doctor right away if you have any of the following symptoms of lactic acidosis. If you have trouble breathing, call 911 right away or go to the nearest emergency room. extreme tiredness weakness decreased appetite nausea vomiting trouble breathing dizziness lighthea Continue reading >>
Clarifying Metformin's Role And Risks In Liver Dysfunction.
Abstract OBJECTIVES: To explore why some clinicians hesitate to use metformin in patients with liver disease and whether routine monitoring of transaminases before and during metformin therapy is substantiated. DATA SOURCES: A Medline literature search was conducted (1966 to June 2008) using the terms metformin, lactic acidosis, liver disease, chronic liver disease, hepatotoxicity, hypoxia, risks, and predisposing factors. DATA SYNTHESIS: Manufacturer prescribing information and some current medical and lay press literature caution against metformin use in patients with liver disease. This recommendation is interpreted variably by different prescribers, with some believing that the caution implies metformin can cause or worsen liver injury. Others believe that liver disease predisposes patients to developing lactic acidosis. A clearer understanding of how and when to screen for liver dysfunction in patients before and during metformin therapy is thus warranted. CONCLUSION: Metformin does not appear to cause or exacerbate liver injury and, indeed, is often beneficial in patients with nonalcoholic fatty liver disease. Nonalcoholic fatty liver frequently presents with transaminase elevations but should not be considered a contraindication to metformin use. Literature evidence of liver disease being associated with metformin-associated metabolic acidosis is largely represented by case reports. Most such patients had cirrhosis and were also actively using alcohol. Patients with cirrhosis, particularly those with encephalopathy, may have arterial hypoxemia, which heightens the risk of developing lactic acidosis. For this reason, identifying patients with cirrhosis before initiating metformin seems prudent. Because cirrhosis can exist in the face of normal liver transaminases, Continue reading >>
Continuation Of Metformin Use After A Diagnosis Of Cirrhosis Significantly Improves Survival Of Patients With Diabetes
Abstract The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment. This study investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with diabetes. Diabetic patients diagnosed with cirrhosis between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were identified (n = 250). Data were retrospectively abstracted from the medical record. Survival of patients who continued versus discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox's proportional hazards analysis. Overall, 172 patients continued metformin whereas 78 discontinued metformin. Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11.8 vs. 5.6 years overall, P < 0.0001; 11.8 vs. 6.0 years for Child A patients, P = 0.006; and 7.7 vs. 3.5 years for Child B/C patients, P = 0.04, respectively). After adjusting for other variables, continuation of metformin remained an independent predictor of better survival, with an HR of 0.43 (95% CI: 0.24-0.78; P = 0.005). No patients developed metformin-associated lactic acidosis during follow-up. Conclusion: Continuation of metformin after cirrhosis diagnosis reduced the risk of death by 57%. Metformin should therefore be continued in diabetic patients with cirrhosis if there is no specific contraindication. (Hepatology 2014;60:200 Continue reading >>
Metformin Effects On The Liver
Physicians commonly prescribe Metformin if you have Type 2 diabetes and need help controlling your blood sugar. It reduces how much glucose you absorb from food and the amount your liver produces. On rare occasions, however, Metformin causes liver dysfunction and a serious metabolic condition involving the liver. For this reason, physicians exercise caution when prescribing Metformin to patients with liver disease. Video of the Day In healthy individuals, the liver produces glucose to keep blood sugar stable when you haven't eaten for several hours. Uncontrolled glucose production in the liver may cause high blood sugar in individuals with Type 2 diabetes. Researchers discovered that Metformin blocks critical enzymes involved in signaling the liver to produce glucose, thereby decreasing blood sugar levels. Their work was reported in the February 2013 edition of the journal "Nature." Lactic Acid Production Your muscles, brain, skin and other tissues produce a substance called lactic acid. Under normal circumstances, your liver and kidneys remove lactic acid from the blood and convert some of it to glucose. If a life-threatening metabolic condition known as lactic acidosis occurs, lactic acid levels increase faster than the liver can keep up with. Though its mechanism is unclear, Metformin causes lactic acidosis in a small segment -- up to 1 percent -- of patients, according to NYU Langone Medical Center. Almost all reported cases occurred in patients with underlying metabolic issues, such as liver or kidney disease. According to LiverTox, a publication of the U.S. National Library of Science drug database, Metformin may occasionally cause mild liver toxicity, characterized by minor elevations in liver enzymes. It occurs in less than 1 percent of the patients taking Metfo Continue reading >>
Consensus Statement On Dose Modifications Of Antidiabetic Agents In Patients With Hepatic Impairment Gangopadhyay Kk, Singh P - Indian J Endocr Metab
The liver has an important role in carbohydrate metabolism. It is responsible for the balance of blood glucose levels by means of neoglucogenesis and glycogenolysis. [1] The metabolic homeostasis of glucose is impaired in the presence of chronic liver disease (CLD) resulting in insulin resistance (IR), glucose intolerance, and diabetes. [1] , [2] , [3] According to a report, the prevalence of diabetes mellitus (DM) in patients with CLD is reportedly 18%–71%. [4] In another report, glucose intolerance is seen in up to 80% of patients with CLD and diabetes in 30%–60%. [5] Moreover, in case of liver cirrhosis, glucose intolerance and diabetes is present in approximately 96% of the patients. [6] Hence, diabetes and CLD often coexist and existing evidence suggests that CLD increases complications and premature mortality in patients with diabetes. [7] Association between diabetes and CLD is given in [Figure 1] . Figure 1: Relationship between diabetes and chronic liver disease. HCV: Hepatitis C Virus; HCC: Hepatocellular Carcinoma; NAFLD: Nonalcoholic Fatty Liver Disease; DM: Diabetes Mellitus; T2DM: Type 2 Diabetes Mellitus In contrast to the involvement of liver disease in causing diabetes, diabetes has also been proposed as a risk factor for both CLD and hepatocellular carcinoma (HCC). In fact, diabetes, by most estimates, is now the most common cause of liver disease cryptogenic cirrhosis and has become the third leading indication for liver transplantation in the United States. DM has been commonly associated with nonalcoholic fatty liver disease (NAFLD), including its most severe form, nonalcoholic steatohepatitis (NASH). NASH is a chronic necroinflammatory condition that can lead to liver fibrosis, cirrhosis, and subsequently to HCC. [8] In addition, there is an u Continue reading >>
Protective Effect Of Metformin On Toxicity Of Butyric Acid And Arsenic In Isolated Liver Mitochondria And Langerhans Islets In Male Mice: An In Vitro Study
Ahangarpour, A., zeidooni, L., Rezaei, M., Alboghobeish, S., samimi, A., Oroojan, A. (2017). Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study. Iranian Journal of Basic Medical Sciences, 20(12), 1297-1305. doi: 10.22038/ijbms.2017.9567 Akram Ahangarpour; Leila zeidooni; Mohsen Rezaei; Soheila Alboghobeish; Azin samimi; Ali Akbar Oroojan. "Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study". Iranian Journal of Basic Medical Sciences, 20, 12, 2017, 1297-1305. doi: 10.22038/ijbms.2017.9567 Ahangarpour, A., zeidooni, L., Rezaei, M., Alboghobeish, S., samimi, A., Oroojan, A. (2017). 'Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study', Iranian Journal of Basic Medical Sciences, 20(12), pp. 1297-1305. doi: 10.22038/ijbms.2017.9567 Ahangarpour, A., zeidooni, L., Rezaei, M., Alboghobeish, S., samimi, A., Oroojan, A. Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study. Iranian Journal of Basic Medical Sciences, 2017; 20(12): 1297-1305. doi: 10.22038/ijbms.2017.9567 Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study 2 ; Mohsen Rezaei 3 ; Soheila Alboghobeish 4 ; Azin samimi 2 ; Ali Akbar Oroojan 5 1Health Research Institute, Diabetes Research Center, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2Department of Toxicology, Continue reading >>
The Effect Of Metformin On Liver Function Tests In The Diabetes Prevention Program
The Effect of Metformin on Liver Function Tests in the Diabetes Prevention Program Metformin may lower aminotrans Metformin may lower aminotransferase concentrations in non-alcoholic fatty liver disease (NAFLD), which is common in people with type 2 diabetes, obesity and/or insulin resistance. In the Diabetes Prevention Program (DPP), 2153 adults with impaired glucose tolerance, an overweight group likely to be at high risk for NAFLD, were randomized to metformin (MET; n=1072) or placebo (PLAC; n=1081) between 1996 and 1999 and followed for an average of 3.2 years. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured at baseline, 3 and 6 months and every 6 months thereafter. Regression models controlling for co-variates and repeated measures were used to evaluate the effect of metformin on AST or ALT in the whole group and a sub-group reporting no alcohol use at baseline. Incidence of development of abnormal AST or ALT was calculated using sex-specific NHANES III 95th percentile for AST and ALT among participants below those cut-offs at baseline. AST and ALT were lower in the MET vs. PLAC groups (geometric means averaged over time for AST, 21.7 vs. 22.2 U/l, p=0.03; for ALT, 19.3 vs. 20.1 U/l, p=0.004) and remained so after adjustment for age, sex, BMI, fasting glucose and insulin at baseline (adjusted geometric means averaged over time (for AST, 22.1 vs. 22.6 U/l, p=0.02; for ALT, 19.7 vs. 20.7 U/l, p=0.001). ALT (but not AST) remained significantly lower in the MET group after separate adjustment for glucose and insulin at each visit, but not after separate adjustment for weight loss (19.5 vs. 20.3 U/l, p=0.2), indicating the effect on ALT is mediated via weight loss. In the sub-group with no alcohol use at baseline, ALT was significantly Continue reading >>
Metformin-induced Hepatotoxicity
Metformin is the first choice oral antidiabetic drug for type 2 diabetes and currently the most consumed. Although gastrointestinal intolerance is frequent, metformin-induced hepatotoxicity is rare. Fewer than 10 cases have been reported (1). In all of those cases, metformin was associated with concomitant intake of other potentially hepatotoxic drugs. We present what we feel may be the first documented case of hepatotoxicity due to metformin with no other drug interference. A 61-year-old man was admitted to the hospital with a 3-day history of painless jaundice. He had no history of liver disease or toxic habits and denied previous consumption of drugs or herbal products, but had been taking metformin (1,700 mg/day for 6 weeks) after being diagnosed with type 2 diabetes. Laboratory tests showed a mixed pattern of liver damage (total bilirubin 2.9 mg/dL, direct bilirubin 2.4 mg/dL, aspartate aminotransferase [AST] 290 units/L [≤40], alanine aminotransferase [ALT] 861 units/L [≤35], γ-glutamyltransferase [GGT] 861 units/L [≤35], and alkaline phosphatase [ALP] 622 units/L [≤120]). International normalized ratio and eosinophil counts were normal. Diagnostic work-up ruled out viral hepatitis A, B, and C, as well as autoimmune and metabolic liver disease (negative antinuclear antibodies, anti-mitochondrial antibodies, smooth muscle antibodies, anti-liver/kidney microsomal antibodies; normal ceruloplasmin, α-1 antitrypsin, copper). Abdominal ultrasound and cholangio-MRI showed no pathological findings. The patient refused a liver biopsy. After stopping metformin, the patient's clinical condition progressively improved and liver enzymes normalized in 30 days. He was discharged with only recommendations to modify his lifestyle. Six weeks after discharge, the patient a Continue reading >>
The Liver Disease Epidemic You Need To Know About
Metformin Because of the central role of insulin resistance in development of NAFLD and NASH, it makes sense to evaluate insulin-sensitizing drugs for their prevention.36,37 No oral antidiabetic drug has as broad a spectrum of action, and as hefty a safety record, as the drug metformin, which is finding a host of new applications outside of diabetes itself.38,39 Studies of metformin for NAFLD and NASH have multiplied in the past few years with almost uniform success. Metformin in the amount of 500 mg three times daily for 6 months produced dramatic improvements in liver blood flow and velocity as detected by Doppler ultrasound exams.40 A similar dose of metformin (20 mg/kg body weight for one year, or approximately 1,450 mg/day for a 160-pound person) produced reductions in blood markers of liver cell death, though the improvement lasted only 3 months.41 On the other hand, improved insulin sensitivity has repeatedly been shown in patients with NASH and NAFLD who take metformin, and many studies have now shown sustainable improvements in liver chemistry measurements.36,42 And a recent study showed significant reduction in the prevalence and severity of fatty liver after 6 months’ treatment with 850 mg metformin twice daily in obese adolescents, an extremely challenging group of patients.43 Metformin is an ideal drug for combination studies because of its safety and compatibility with other therapies. A 2008 study revealed that the combination of metformin with the potent antioxidant N-acetyl cysteine (NAC) for 12 months improved both liver chemistry results and measurements of insulin resistance.44 Liver tissue evaluated by biopsy also showed improved appearance for the earlier signs of disease. Finally, in 2010 we learned of an entirely new mechanism by which metformi Continue reading >>
