Two popular diabetes drugs outperformed each other in a large clinical trial

News release

Wednesday, September 21, 2022

NIH-funded researchers complete first study comparing commonly used type 2 diabetes drugs.

In a large clinical trial that directly compared four drugs commonly used to treat type 2 diabetes, researchers found that insulin glargine and liraglutide did the best of the four drugs approved by the Food and Drug Administration of the US to keep blood glucose levels in the recommended range. Blood glucose management is a key component of keeping people with type 2 diabetes healthy. The four drugs evaluated were added to treatment with metformin, which is the first-line drug to treat type 2 diabetes. The trial was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health.

More than 37 million Americans have diabetes, and about 90 to 95 percent of them have type 2 diabetes. People with diabetes who keep their blood glucose levels in a near-normal range usually have , a much lower risk of developing diabetes complications such as nerve, kidney and eye disease. Most people with type 2 diabetes require more than one medication to control their blood sugar levels over time.

Although there is general agreement among health professionals that metformin combined with diet and exercise is the best early approach to diabetes care, there is no consensus on what to do next to maintain high glucose under control.

Launched in 2013, the Lowering Blood Glucose in Diabetes: A Comparative Effectiveness Study (GRADE) was conducted at 36 study centers in the US. It was designed to compare four major drugs approved by the FDA at the time GRADE began to treat diabetes in combination with metformin. The main results were published in a couple of papers a The New England Journal of Medicine.

“This study was designed to provide healthcare providers with important information on how to guide the long-term management of type 2 diabetes,” said Dr. Henry Burch, GRADE Project Scientist at NIDDK. “This is an integral step towards precision medicine for diabetes care, as these results can now be used in the decision-making process for each individual patient in light of their levels of diabetes control. glucose, how the medication is tolerated, and the person’s other health considerations.”

The study included 5,047 people with type 2 diabetes from various racial and ethnic groups who were already taking metformin. Participants were randomly placed into one of four treatment groups. Three groups took metformin plus a drug that increased insulin levels, sitagliptin, liraglutide or glimepiride. The fourth group took metformin and insulin glargine U-100, a long-acting insulin.

After an average of four years of follow-up, the study found that participants taking metformin plus liraglutide or insulin glargine achieved and maintained their target blood levels for longer compared to sitagliptin or glimepiride. This translated into approximately six months longer with blood glucose levels in the target range compared to sitagliptin, which was the least effective at maintaining target levels. Treatment effects did not differ by age, sex, race, or ethnicity.

However, none of the combinations overwhelmingly outperformed the others. Although average blood sugar levels decreased during the study, nearly three-quarters of all participants failed to maintain their blood glucose target over four years, underscoring the difficulty of maintaining recommended targets in many patients with type 2 diabetes.

“GRADE effectively shows which drugs worked best to achieve and maintain blood glucose goals over time, but we need to establish even more effective strategies for long-term maintenance of acceptable glucose levels,” he said. the Dr. David M. Nathan, president of the GRADE study. director of the Massachusetts General Hospital Diabetes Center, Boston. “We still have more work to do, such as evaluating other interventions and treatment combinations to help people with type 2 diabetes achieve long-term glucose control.”

The study also looked at the effects of the treatments on the development of diabetes-related cardiovascular disease. The researchers found that participants in the liraglutide group were less likely to have any cardiovascular disease overall compared to the other groups.

The study also looked at side effects of the drugs, finding:

  • Severe hypoglycemia, often called a low blood glucose reaction, was generally uncommon but affected more participants assigned to glimepiride (2.2%).
  • Gastrointestinal symptoms were more common with liraglutide than with the other three treatment groups.

Also, on average, participants in all treatment groups lost weight. Over four years, people in the liraglutide and sitagliptin arms lost more weight (an average of 7 and 4 pounds, respectively) than those in the glargine and glimepiride arms (less than 2 pounds).

“With so many treatment options available for type 2 diabetes, it can be difficult for health care providers and patients to know which drug is best for which person,” said NIDDK Director Dr. Griffin P .Rodgers. “NIDDK is especially poised to support comparative effectiveness trials like GRADE to help providers make evidence-based recommendations that lead to better health for their patients and all people living with type 2 diabetes “.

A type of diabetes drug now available called SGLT2 inhibitors was not approved by the FDA at the launch of GRADE recruitment and was not included in the study.

The GRADE study was supported by a grant from NIDDK (U01DK098246). Additional support was provided by the National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences; National Center for the Advancement of Translational Sciences; the Centers for Disease Control and Prevention; and the American Diabetes Association. The Department of Veterans Affairs provided resources and facilities. Material support in the form of donated drugs and supplies has been provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics, and Sanofi. number: NCT01794143.

The NIDDK, part of the NIH, conducts and supports basic and clinical research and research training on some of the most common, serious and disabling conditions affecting Americans. The Institute’s research interests include diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and renal, urological and hematological diseases. For more information, visit

About the National Institutes of Health (NIH):NIH, the nation’s medical research agency, includes 27 institutes and centers and is a component of the US Department of Health and Human Services. NIH is the lead federal agency that conducts and supports basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit

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