Two popular diabetes drugs outperform others in 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 diabetes type 2In this study, researchers found that insulin glargine and liraglutide performed the best of four drugs approved by the US Food and Drug Administration for keeping blood sugar levels in the recommended range. Blood glucose management is a key component of keeping people with type 2 diabetes healthy. All four drugs evaluated were combined in treatment with metformin, a first-line drug for the treatment of type 2 diabetes. the trial was funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Part of National Institutes of Health,

More than 37 million Americans have diabetes, and about 90 to 95% of them have type 2 diabetes. People with diabetes who keep their blood sugar levels roughly within the normal range usually have a much lower risk of developing complications of diabetes such as nerve, kidney and eye diseases. Most people with type 2 diabetes need more than one medicine to control blood sugar levels over time.

While there is general consensus among health care professionals that metformin along with diet and exercise is the best initial approach in the care of diabetes, there is no consensus on what to do next to keep high blood sugar under control.

Launched in 2013, Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study The study was conducted in 36 US centers. It was designed to compare the four major drugs approved by the FDA when GRADE started treating diabetes in combination with metformin. Major results published in two papers New England Journal of Medicine,

“This study was designed to provide health care providers with important information on how to guide the long-term management of type 2 diabetes,” said Dr. Henry Burch, NIDDK’s project scientist for GRADE. “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 patient in light of their level of glucose control, how well the drugs are tolerated. and other health considerations of the individual.”

The study enrolled 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 raises 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 the longest time compared to sitagliptin or glimepiride. This translated to about six months longer with blood sugar 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, no combination outperformed the others. Although average blood sugar levels decreased over the course of the study, nearly three-quarters of all participants were unable to maintain blood sugar goals over four years, underscoring the difficulty in maintaining recommended goals in many patients with type 2 diabetes. We do.

“GRADE effectively shows which drugs work best at achieving and maintaining blood glucose targets over time, but we need to establish even more effective strategies for the long-term maintenance of acceptable glucose levels.” GRAD study chair Dr. David M. Nathan, 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 treatment on the development of diabetes-related heart disease. The researchers found that participants in the liraglutide group were less likely than the other groups to experience any heart disease overall.

The study also examined the side effects of the drugs, which found:

  • Severe hypoglycemia, often referred to as a low blood sugar 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.

In addition, 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 medication is best for which individual,” said NIDDK director Dr. Griffin P. Rodgers. “The NIDDK is uniquely positioned to support comparative effectiveness trials such as GRADE to help providers make evidence-based recommendations that lead to better health for their patients and for all people with type 2 diabetes.”

A no longer available type of diabetes drug called an SGLT2 inhibitor was not approved by the FDA at the start of grad recruitment and was not included in the study.

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

NIDDKPart 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 hematologic diseases. visit for more information,

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

NIH… Turning Discovery into Health


Be the first to comment

Leave a Reply

Your email address will not be published.