Common diabetes drug found safe for most diabetics with kidney disease

June 05, 2018

Results of a large-scale study suggest that the oral diabetes drug metformin is safe for most diabetics who also have chronic kidney disease (CKD). The study of more than 150,000 adults by Johns Hopkins Medicine investigators found that metformin's association with the development of a life-threatening condition called lactic acidosis was seen only among patients with severely decreased kidney function.

A report on the study appeared online June 4 in JAMA Internal Medicine.

Metformin is the first-line medication for treatment of type 2 diabetes in adults and the fifth most commonly used drug in the United States. However, there has been a longstanding concern in the medical community about prescribing metformin for people with both diabetes and CKD because it may cause lactic acidosis, says senior study author Morgan Grams, M.D.,Ph.D., M.H.S., an associate professor of medicine and epidemiology at the Johns Hopkins University School of Medicine. Lactic acidosis is a rare but serious complication, occurring when lactate--a product of glucose breakdown--builds up in the bloodstream, producing symptoms such as severe muscle pain, cramps, nausea and weakness. Because patients with CKD may be at increased risk of metformin-associated lactic acidosis, health care providers historically avoided prescribing metformin in this population.

The Food and Drug Administration recently revised its labeling of metformin so the drug could be used more by CKD patients, says Grams, and some regulatory and professional society guidelines cautiously support use of the drug by diabetic patients with moderate kidney disease. But data addressing the drug's safety for patients with moderate to severe kidney disease had been inconclusive, she says.

A better assessment of acidosis risk could "provide reassurance that millions of people with diabetes and CKD may be able to safely use metformin," Grams says. Past studies show that metformin has multiple benefits beyond controlling blood sugar, including less weight gain, a lower risk of heart attack and even higher long-term survival than other medications that patients take to control blood sugar. About 380 million people worldwide and 29 million people in the United States are affected by diabetes. Approximately 19 percent--or around 5 million--of those in the U.S. with diabetes also have CKD, Grams says.

"Our study demonstrates that the first-line and common diabetes medication is safer in patients with CKD than once thought," Grams says. "From a public health perspective, the potential benefits of using metformin for patients with diabetes and CKD are vast, given the increasing number of people affected with both diseases worldwide."

For the new study, Grams and her co-authors analyzed 2004-2017 medical records from a group of 75,413 patients with diabetes managed by Geisinger Health System in Pennsylvania. They looked at patients' estimated glomerular filtration rates (eGFRs--a measure of kidney function), medications prescribed for diabetes management, hospitalizations for acidosis, demographic information, cigarette smoking status and presence of cardiovascular disease.

The research team used computer-based statistical models to analyze the risk of developing acidosis among metformin users compared with nonusers. The researchers adjusted for conditions such as cardiovascular disease and smoking status.

Overall, Grams and her colleagues found an association between metformin use and acidosis only in patients with severely decreased kidney function, defined as an eGFR of less than 30 mL/min/1.73 m2. A normal eGFR is considered to be over 90 mL/min/1.73 m2. The researchers observed more than double the risk in patients with severely decreased kidney function who used another type of diabetes medication.

In addition, the researchers compared new metformin users with new users of another class of diabetes medications called sulfonylureas within different categories of CKD stages. They replicated their results in a group of 82,017 patients from MarketScan--a database of inpatient and outpatient claims data from 350 private health systems--studying records from 2010 to 2014.

The Geisinger patients averaged age 60, and 51 percent were female. Of the patients, 45 percent (34,095) were taking metformin at enrollment in the study and 13,781 of the remaining patients were subsequently prescribed metformin during a 5.7-year follow-up period.

Among the Geisinger participants, there were 2,335 hospitalizations for acidosis over the study period. Compared with alternative forms of blood sugar management, metformin use was not associated with acidosis overall, nor was it associated with acidosis among patients with eGFR levels of 45 to 59 mL/min/1.73 m2 (considered mildly to moderately decreased kidney function) or among patients with eGFR levels of 30 to 44 mL/min/1.73 m2 (considered moderately to severely decreased kidney function).

However, metformin use was associated with an increased risk of acidosis at an eGFR level of less than 30 mL/min/1.73 m2.

These results were consistent when new metformin users were compared with new sulfonylurea users and with the MarketScan group of patients. There were 67,578 new metformin users in this group, and 14,439 new sulfonylurea users. There were 238 acidosis events among metformin users and 94 among sulfonylurea users. Lower eGFR was a risk factor for acidosis in both groups.

"Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2," Grams says.

While the researchers say these data are promising, they caution that patients receiving metformin could have different underlying acidosis risk than patients who did not receive metformin, and that most of the study sample was white, which may limit generalizability by race.

Metformin, beyond having potential health benefits, is relatively inexpensive. The medication can be obtained for $4 per month for the 500 milligram dose. In contrast, some of the newer diabetes agents can cost more than $400 per month.
-end-
Contributing authors were Benjamin Lazarus, Aozhou Wu, Jung-Im Shin, Yingying Sang, G. Caleb Alexander, Alex Secora and Josef Coresh of Johns Hopkins; Lesley Inker of Tufts Medical Center in Boston; and Alex Chang of the Kidney Health Research Institute at Geisinger Health System, in Danville, Pennsylvania.

Grams receives funding from the National Institutes of Health via grants R01DK100446 and K08DK092287; Sang and Coresh receive funding from the National Institutes of Health via grant R01DK100446.

Johns Hopkins Medicine

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.