When diet and exercise fail in treating type 2 diabetes in patients, metformin may be the drug of choice, according to guideline recommendations by members of the American College of Physicians (ACP). ACP members found metformin to have fewer side effects than sulfonylureas, and the cost of the drug may also be less.

“Diabetes is a major cause of morbidity in the U.S.,” Amir Qaseem, MD, PhD, director of clinical policy at the American College of Physicians told Cardiovascular Business in an interview. Currently, diabetes has a price tag close to $200 billion, making it important to study the safety of current treatments for the common comorbidity.

For type 2 diabetics, tissues are resistant to the effects of insulin and blood sugar levels are often high; however, some of these woes can be overcome with diet and exercise.

“You must start off with lifestyle modifications—diet, exercise and weight loss,” Qaseem urged. Only when diet, exercise and weight loss fail is it appropriate to add on an oral pharmacological agent in type 2 diabetics. “But, lifestyle modifications are most important. I am not saying that we forget about that,” he said.

In the current guidelines, ACP members studied the safety and effectiveness of available drugs to treat type 2 diabetes to help clinicians make more informed decisions when treating this patient population. During their review, members looked at various drug classes, including: metformin, sulfonylureas, meglitinides, thiazolidinediones, inhibitors of dipeptidyl peptase-1 and glucagon-life peptide-1 receptor antagonists (all of which are approved by the FDA).

“What we now recommend is for physicians to add oral pharmacologic therapy in type 2 diabetes patients where diet and exercise have not adequately improved hyperglycemia,” Qaseem said. “Once you decide to start pharmalogic therapy, ACP would recommend metformin as the initial strategy.”

While Qaseem and colleagues found that most diabetes medications reduced levels of hyperglycemia to similar degrees, metformin was more effective in terms of reducing blood sugar levels when used alone or in combination with other drugs. Additionally, metformin had fewer adverse effects and was not associated with weight gain. Instead, the drug was linked to weight loss.

“Metformin was also associated with fewer hypoglycemic episodes, which can be very dangerous,” Qaseem noted. “When we looked at the evidence, we have concluded that metformin is the drug of choice for patients with type 2 diabetes when used on top of lifestyle modifications."

However, there is another piece to this puzzle. What happens when hyperglycemia remains persistent, even when metformin is prescribed? In these cases, it is recommended that a second agent be prescribed as an adjunct to metformin when lifestyle modifications and monotherapy won’t cut it.

Qaseem said that dual-therapy regiments have been found to be more effective than monotherapy; however, it is still unknown what the perfect combination is.

“Metformin is a better drug,” Qaseem offered. “It is more effective and is cheaper as well.” Additionally, Qaseem said that fewer adverse effects were associated with metformin, and he noted that the drug reduced weight gain and reduced LDL-cholesterol.

However, metformin may be contraindicated in certain patients including those with:

• Impaired kidney function;

• Liver disease; and
• Heart failure.

“If metformin is contraindicated you must then look to other medications,” Qaseem said. “There are several other medications and you must look at the adverse event profiles to select medications that may work better.”

Qaseem said that metformin is also cheaper compared with other drug classes to treat type 2 diabetes, which he said can be “extremely expensive.” For example, a 500 mg once daily dose of brand name metformin may run patients between $26 to $75, while a 15 mg once daily dose of pioglitazone, a thiazolidinedione, would cost patients between $126 to $200, according to the analysis. DPP-4 inhibitors such as a 100 mg once daily dose of sitagliptin run patients over $200, but a generic brand of a 500 mg once daily dose of metformin would cost patients between $5 and $25—cheaper than most other drug classes surveyed.

“[Metformin] is cheaper than most other pharmacologic agents, has better effectiveness and is associated with fewer adverse effects; of note, it does not result in weight gain,” members of the ACP summed.

Guidelines were published in the Feb. 7 issue of the Annals of Internal Medicine.