Which Blood Sugar Meds Work Best Against Type 2 Diabetes?

You have type 2 diabetes, and you are already taking an old standby drug, metformin. But you still need help controlling your blood sugar levels. Which medication would be the best?

New research pitted several diabetes drugs against each other and came up with an answer: The diabetes drugs Lantus and Victoza were better at controlling blood sugar over time than Amaryl or Januvia.

"We've known that type 2 diabetes is a progressive disease, and these medications, in general, do not reduce or obliterate progression, and that the ability of these medications to slow the rise in glucose varies amongst them," explained Dr. Steven Kahn, a professor of medicine, metabolism, endocrinology and nutrition at the University of Washington in Seattle. He is a member of the executive committee that oversaw the trial.

The goal was to see which of these drugs kept average blood sugar levels in the recommended target range, at an A1C level of less than 7%. A1C blood tests are a standard means of gauging long-term blood sugar control.

"When we look at the rise in A1C over time, it's clear that there are initial beneficial impacts of one drug over the other, but they tend to fail at a very similar rate," Kahn said. "So, beyond the first couple of years, all the failure seems to be occurring at the same rate, but overall failure was less with Lantus and Victoza."

Lantus (insulin glargine) and Victoza (liraglutide) are both injectable drugs, while Amaryl (glimepiride) and Januvia (sitagliptin) are pills.

The study, which was funded by the U.S. National Institutes of Health, included more than 5,000 people with type 2 diabetes, average age 57. The participants, 20% of whom were Black and 18% of whom were Hispanic, were randomly assigned to one of the four drugs along with metformin in the trial, which ran an average of four years.

The researchers found that Lantus and Victoza were the most effective in keeping A1C levels under 7%, while Amaryl or Januvia had the lowest effect and higher odds of letting A1C levels rise above 7%.

The results were similar across gender, race, ethnicity and age group.

Other findings included:

• Patients given Victoza and Januvia were more likely to lose weight than those taking Amaryl. Those taking Lantus maintained a stable weight.

• Victoza caused more gastrointestinal side effects, such as nausea, abdominal pain and diarrhea, than the other drugs. Amaryl was linked to a higher risk for low blood sugar than the other drugs.

• Victoza was linked to a lower risk of heart attack, stroke and other heart and vascular complications than the other drugs.

Dr. Caroline Messer, an endocrinologist at Lenox Hill Hospital in New York City, said the study confirms that these medications are appropriate and should be used as a second-line treatment after metformin, or as a first-line treatment if metformin isn't tolerated.

Messer noted that although some of the newer drugs are expensive, they are covered by most health insurance plans.

"I think the only disservice of the study is that I don't want people to start thinking that you should be using insulin [Lantus] as a second-line treatment," she explained. "I think that it does a disservice, because if people are reaching for insulin too quickly because of this trial, that would be a shame."

The findings were presented Monday at the virtual annual meeting of the American Diabetes Association. Findings presented at medical meetings should be considered preliminary until published in a peer-reviewed journal.

Dr. Joel Zonszein, an emeritus professor of medicine at Albert Einstein College of Medicine in New York City, was not surprised by the findings, but thinks the trial is outdated.

"It certainly proves that Victoza and Lantus are better medications to improve blood sugar control when metformin is not enough," he said.

The problem with the study is that it didn't include other drugs that were approved by the U.S. Food and Drug Administration when the study began, so there may be more effective drug combinations that are yet to be tested, Zonszein said.

"We need to know what the best combination is for treatment of diabetes early in the disease and not to use the antiquated step-up approach — what to do when the medication fails? We have an excellent choice of medications, and there is no reason to have individuals with diabetes not well-treated," he added.

And when managing diabetes, treating blood sugar is not the only consideration, Zonszein noted.

"We treat each patient and individualize regimens accordingly. Treatment includes obesity, high cholesterol and hypertension, among others. We aim to improve and prolong a good quality of life," he said. "For instance, the weight loss found with Victoza is important for many, and not found with the other agents in the study. Victoza's gastrointestinal side effects are also well-known, and these are decreased when using newer weekly drugs."

Although blood sugar levels are important, treatment aims to avoid or delay the complications of diabetes, Zonszein said.

Because stroke and heart attack are the common causes of death among diabetes patients, treatment should include medications that prevent heart attack, stroke and other heart and vascular complications, as well as kidney disease.

"The... trial is therefore outdated, and doesn't help people or their health care providers to make decisions in 2021 — the train has left the station," Zonszein said.

"Treatment of diabetes has shifted towards individualizing therapy, using proper medications from the get-go. We now use medications that do not cause low blood sugar or need frequent blood sugar checking. Certainly, we use medications that can help with weight loss and cause less cardiovascular complications," he explained.

Kahn said he is all for individualized treatment for type 2 diabetes. He also wishes that drug companies would do head-to-head trials of the newer drugs to determine the best combination treatment.