Two Popular Diabetes Drugs Outperformed Others in Massive Clinical Trial


Press release

Wednesday, September 21, 2022

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

In a large clinical trial directly comparing four drugs commonly used to treat Type 2 diabetes, researchers found that insulin glargine and liraglutide were the best of four medications approved by the US Food and Drug Administration to keep blood sugar levels within the recommended range. Managing blood sugar is a key part of maintaining good health for people with type 2 diabetes. 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)which is part of the National Institutes of Health.

More than 37 million Americans have diabetes, and about 90-95% of them have type 2 diabetes. People with diabetes who keep their blood sugar levels within a near-normal range generally have a much higher risk low to develop diabetes complications such as nerve, kidney and eye diseases. Most people with type 2 diabetes need more than one drug to control their blood sugar over time.

Although there is a general consensus among healthcare professionals that metformin plus diet and exercise is the best early approach in diabetes care, there is no consensus. on what to do next to better control high blood sugar.

Launched in 2013, the Blood Glucose Lowering Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) was conducted at 36 US study centers. It was designed to compare four major drugs approved by the FDA at the time GRADE began treating diabetes in combination with metformin. The main results were published in a pair of articles in 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, NIDDK Project Scientist for GRADE. “This is an essential 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 level of blood sugar control. , drug tolerance and other health considerations.

The study recruited 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 medicine 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 reached 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 in 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 decreased over the course of the study, nearly three-quarters of all participants were unable to maintain the four-year blood sugar goal, underscoring the difficulty of maintaining recommended goals. in many patients with type 2 diabetes.

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

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

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

  • Severe hypoglycaemia, often called hypoglycaemia reaction, was generally uncommon but affected more participants on glimepiride (2.2%).
  • Gastrointestinal symptoms were more frequent with liraglutide than with the other three treatment groups.

Additionally, 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 the glargine and glimepiride arms (less than 2 pounds).

“With so many treatment options available for type 2 diabetes, healthcare providers and patients can struggle to know which medication is best for which person,” said NIDDK director Dr. Griffin. P. Rodgers. “The NIDDK is uniquely positioned to support comparative effectiveness trials like 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 type of diabetes medication now available called SGLT2 inhibitors was not approved by the FDA when the GRADE enrollment was launched and was not included in the study.

The GRADE study was funded by a grant from the 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 the resources and facilities. Material support in the form of drug and supply donations was 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):The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part 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 studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit

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