Two popular diabetes drugs outperformed others in large clinical trial
October 6, 2022
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BATON ROUGE, Louisiana — In a large clinical trial that directly compared four drugs commonly used to treat type 2 diabetes, researchers found that insulin glargine and liraglutide performed the best of four medications approved by the U.S. Food and Drug Administration to maintain blood glucose levels in the recommended range. Blood glucose management is a key component of keeping people with type 2 diabetes healthy. All four medications evaluated were added to treatment with metformin, which is the first-line drug to treat type 2 diabetes. The trial, based partly at Pennington Biomedical Research Center, was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a branch of the National Institutes of Health.
More than 37 million Americans have diabetes, and approximately 90 to 95 percent of them have type 2 diabetes. People with diabetes who keep their blood glucose levels in the near-normal range generally have a much lower risk of developing diabetes complications such as nerve, kidney, and eye diseases. Diabetes is difficult to treat, as most people require more than one medication to control blood sugar levels over time.
While there is general agreement among health care professionals that metformin combined with diet and exercise is the best early approach in diabetes care, there is no consensus on what the next best step is to keep high blood glucose in check.
Launched in 2013, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Studywas conducted at 36 U.S. study centers, including Pennington Biomedical Research Center. It was designed to compare four major medications approved by the FDA at the time GRADE started to treat diabetes in combination with metformin. A now-available type of diabetes drug called SGLT2 inhibitors was not approved by the FDA at the launch of GRADE recruitment and was not included in the study. Major results were published in a pair of papers in The New England Journal of Medicine.
Daniel Hsia, MD, associate professor at Pennington Biomedical, served as site principal investigator for the study. “GRADE provides physicians with critical information from real world comparisons of four commonly used medications when added to metformin to treat type 2 diabetes. Some medications may work better for certain patients depending on their own unique characteristics. This study helps us get closer to the goal of providing our patients with precision care for diabetes.”
The study enrolled 5,047 people with type 2 diabetes from diverse 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 achieved and maintained their target blood levels for the longest time compared to sitagliptin or glimepiride. This translated into approximately six months more time with blood glucose levels in the target range compared with sitagliptin, which was the least effective in maintaining target levels. Treatment effects did not differ based on 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 were unable to maintain the blood glucose target over four years, underscoring the difficulty in maintaining recommended targets in many patients with type 2 diabetes.
“There is still much work to do. We need to examine the effect of newer medications that were not tested in GRADE, and we need to go beyond just looking at blood sugar levels but also improving longer term outcomes such as decreasing diabetes-related complications,” Hsia said.
The study also looked at the treatments’ effects on developing diabetes-related cardiovascular disease. Researchers found that participants in the liraglutide group were least likely to experience any cardiovascular disease overall compared to the other groups.
The study also examined 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.
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 the glargine and glimepiride arms (less than 2 pounds).
Pennington Biomedical Executive Director John Kirwan, PhD, noted that this study extends Pennington Biomedical’s important role in the development of novel treatments for diabetes and the care of patients with diabetes. “Pennington Biomedical has been long sought after for our ability to perform clinical trials that test the effectiveness of obesity and diabetes medications, as well as any number of other interventions and therapies such as behavioral and surgical interventions. It is important that we can offer our local residents the opportunity to participate in cutting-edge research and be represented in studies that ultimately impact patients’ lives,” he said.
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 Advancing 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 medications and supplies has been provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics, and Sanofi. ClinicalTrials.gov number: NCT01794143.
About LSU’s Pennington Biomedical Research Center
The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. The Center architected the “Obecity, USA” awareness and advocacy campaign to help solve the obesity epidemic by 2040. The Center conducts basic, clinical, and population research, and is affiliated with Louisiana State University. The research enterprise at Pennington Biomedical includes over 480 employees within a network of 40 clinics and research laboratories, and 13 highly specialized core service facilities. Its scientists and physician/scientists are supported by research trainees, lab technicians, nurses, dietitians, and other support personnel. Pennington Biomedical is located in state-of-the-art research facilities on a 222-acre campus in Baton Rouge, Louisiana. For more information, see https://www.pbrc.edu.