Metformin Ups Survival in T2DM and Cirrhosis

Whether metformin should be discontinued in patients with cirrhosis is an open debate. Some studies point to a protective effect of metformin against liver cancer. Because of concerns over lactic acidosis, though, metformin is often discontinued in patients with cirrhosis.

A new study suggests that continuing metformin after a diagnosis of cirrhosis can decrease the risk of death in patients with diabetes by about 57%.

 “Patients with diabetes who develop cirrhosis and stay on metformin appear to have a better long-term survival than those who are on different anti-diabetic medications, such as insulin, or those that are switched from metformin to insulin,” commented author Lewis Roberts, MB ChB, PhD, Professor of Medicine at the Mayo Clinic College of Medicine in Rochester, Minnesota.   

“Our results suggest that patients with diabetes who develop cirrhosis can continue to be managed on metformin,” he added, “The use of metformin appears to be safe in most patients with cirrhosis.”

Evidence linking metformin to liver injury is “weak,” the authors write. The incidence of lactic acidosis is low in diabetic patients treated with metformin, and is about the same as among diabetic patients not treated with metformin. Moreover, evidence of lactic acidosis in patients with liver disease mainly comes from case reports of patients actively drinking alcohol.

The researchers reviewed medical records from 2000 to 2010 to identify patients receiving metformin when they were given a diagnosis of cirrhosis (N=250). They then compared survival between patients who continued metformin for at least 3 months after diagnosis (172 [68.6%]) with those who discontinued metformin within 3 months after diagnosis (n=78 [31.2%]). Patients were followed for approximately 5 years.

Key results included:

•  78% (n=61) discontinued metformin because of a diagnosis of cirrhosis
• Those who continued metformin had significantly longer survival, compared with those who discontinued it (11.8 vs 5.6 years overall, P < .001)
• Cirrhosis severity did not seem to make a difference (median survival for continued vs discontinued: Child A patients 11.8 vs 6.0 years, P = .006; Child B/C patients 7.7 vs 3.5 years, P = .04)
• Causes of liver disease were: 56.8% NASH, 11.6% alcohol, 12.0% HCV, 2.4% HBV, others 5.6%, and unknown 11.6%
• Only the NASH group experienced the benefits of metformin (median survival in continued [n=98] vs discontinued [n=44]: 12.1 vs 5.1 years, P = .0004)
• Differences in survival were nonsignificant in the alcohol-, HBV-, HCV-, and a combined non–NASH-cirrhosis group
• Continuation of metformin remained an independent predictor of improved survival even after adjusting for potential confounders (HR = 0.43; 95% CI, 0.24-0.78; P = .005)
• No patients developed metformin-associated lactic acidosis

“Our results suggest that metformin is particularly beneficial in reducing death from cirrhosis in persons with diabetes and cirrhosis due to non-alcoholic fatty liver disease,” Roberts pointed out. “Diabetes is a major predisposing factor to non-alcoholic fatty liver disease. Metformin appears to have beneficial effects on cellular metabolic functions, and ameliorates the inflammatory effects of fat in the liver.”

Individuals with significant renal impairment, as well as those with cirrhosis who are drinking heavily should probably not receive metformin, Roberts emphasized. Metformin should also be temporarily suspended in patients undergoing procedures that require intravenous iodinated contrast.

References:

Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014;60:2008-2016.