Insulin and Metformin for Diabetics May Increase Heart Risks: Study

Adding insulin to a metformin regimen for treatment of type 2 diabetes may increase the risk of heart problems and death, according to the findings of a new study.  

Researchers from Vanderbilt University and the Veterans Health Administration published a study in the Journal of the American Medical Association (JAMA) on June 11, which highlights the difficulty of finding a second line of defense against diabetes when metformin, the first drug most doctors prescribe to treat diabetes, fails to control the problem.

The study looked at data on 178,341 metformin monotherapy patients and compared what happened when some added insulin to their treatment to those who added a drug from a class of diabetes drugs known as sulfonylureas, which includes Glucotrol, Diabeta, Micronase and others. The retrospective cohort study used data from the national Veterans Health Administration, Medicare and the National Death Index databases.

Researchers found that patients who were taking metformin and then began taking insulin were 30% more likely to suffer a cardiovascular event than those given a sulfonylurea, though the rate of actual heart attacks and strokes was about the same. However, researchers also found that those given insulin had a 44% higher mortality rate.

The researchers said that they had expected to find the opposite.

“We hypothesized that intensification with insulin would be associated with a lower risk of [cardiovascular disease] or death compared with sulfonylurea, according to the superiority of insulin in achieving glycemic control,” the researchers noted. “These findings require further investigation to understand risks associated with insulin use in these patients.”

Diabetes Drug Side Effects Leave No Clear Choice

The medical community has been conflicted in recent years about what to do with diabetics whose glucose is not controlled after being placed on metformin monotherapy, according to the researchers in this study. Given the ever-increasing numbers of diabetics in the U.S., it is a major medical concern.

“Diabetes mellitus and its complications represent an enormous health care burden and result in nearly 200,000 deaths annually. The American Diabetes Association and the European Association for the Study of Diabetes recommend that, for patients with preserved renal function, treatment begin with metformin and lifestyle changes to achieve a glycated hemoglobin (HBA1c) level of less than or equal to 7%,” the authors note. “Often patients will require a second agent to reach this goal, but there is no consensus regarding which medications to choose…Evidence to inform treatment choices after metformin monotherapy remains limited.”

Researchers listed a number of options that doctors have to choose from, but many of them are linked to side effects and health risks that have raised concerns in recent years.

One of the choices listed, incretin mimetics, are a popular class of diabetes drugs that has recently been linked to an increased concerns over the risks of pancreatic cancer and pancreatitis. The class includes the diabetes drugs Byetta, Januvia, Janumet, Victoza and others.

Byetta (exenatide) was the first member of the incretin mimetic class of diabetes drugs, which was introduced by Amylin Pharmaceuticals in 2005 as a twice daily injection. Novo Nordisk introduced Victoza (liraglutide) in 2010, as a longer acting injectable diabetes drug and Amylin introduced Bydureon (exenatide extended-release) in January 2012 as a once-weekly version of Byetta.

Januvia (sitagliptin) was introduced by Merck as an oral incretin mimetic diabetes drug in 2006, and has become one of the most widely used members of the class. A combination pill containing Januvia and the older diabetes medication metformin was introduced in 2007 under the brand name Janumet.

Amid mounting concerns about the link between the diabetes drugs and cancer, hundreds of product liability lawsuits have been filed by individuals throughout the United States who claim that they were diagnosed with pancreatic cancer after using Byetta, Januvia, Janumet or Victoza.

Just days ago, the consumer watchdog group Public Citizen petitioned the FDA to issue a Victoza recall and ban the drug from the market due to its pancreatitis risks. However, both U.S. and European governmental health experts have raised doubts about the drugs’ links to pancreatic cancer.

Another once-popular diabetes drug, Actos, is also a subject of major concern following studies suggesting that it increases the risk of bladder cancer. Takeda Pharmaceuticals currently faces more than 7,000 product liability lawsuits pending nationwide, which all involve similar allegations that side effects of Actos increase the risk of users developing bladder cancer following long-term use of the diabetes drug.

Throughout the country a number of early Actos trials have been going before juries in state and federal court to help the parties gauge the strengths and weaknesses of their cases. While the drug maker has won a number of cases a federal jury in Louisiana slammed the company with a record-breaking $9 billion punitive damages verdict, finding that the company intentionally withheld information from consumers to hide the drug’s links to bladder cancer.

Actos came to prominence following the fall of GlaxoSmithKline’s Avandia, which was restricted by the FDA after studies suggested it was linked to an increased risk of heart attack. Since then, the FDA has eased some of the restrictions, but the drug has never recovered and is banned in a number of countries worldwide.