ADA2021

#ADA2021 Liraglutide and insulin more effective in maintaining average blood glucose levels than other common diabetes drugs

(PRNewsFoto/American Diabetes Association)

Head-to-head comparison of glucose-lowering medications helps inform individualized
treatment strategies

WASHINGTON, DC (JUNE 28, 2021) –Today, investigators sponsored by the
National Institutes of Health announced findings from the largest and longest study
comparing the effectiveness of common medications to treat type 2 diabetes. Results
of the GRADE study were presented at the virtual 81st Scientific Sessions of the
American Diabetes Association (ADA).

Pubblicità e progresso

Controlling blood glucose levels over time is a major challenge for people with type 2
diabetes, a condition that disproportionally impacts Black and Hispanic people, who are
50% more likely to have diabetes than non-Hispanic white people.1 The GRADE study,
included a highly diverse population of 20% Black and 18% Latino patients. It was
designed to compare the effectiveness of glucose-lowering medications in maintaining
average blood glucose levels in the target range that has been identified to reduce the
risk of long-term complications.

1 https://clinical.diabetesjournals.org/content/30/3/130

GRADE performed a head-to-head comparison of the four most commonly used
classes of medications used in conjunction with metformin and looked at their ability to
keep average blood glucose levels in the recommended target range, as indicated by
an A1C level (a measurement of average blood glucose) of less than 7%. Medications
in addition to metformin, which is recommended by the ADA for initial use to treat type 2
diabetes, are often needed to treat type 2 diabetes to help lower A1C levels. The
comparison included two oral medications, the sulfonylurea glimepiride and the DPP-4
inhibitor sitagliptin, and two injectable medications, insulin glargine and the GLP-1
receptor agonist liraglutide. The effects of each of the four medications on diabetes
complications and side effects were also examined.

The study enrolled more than 5,000 patients with type 2 diabetes with an average age
of 57 years and an average duration of diabetes of four years. Approximately 1,250
were randomly assigned to each of the four medications. GRADE was conducted for an
average of five years and maximum of more than seven years.

Results of GRADE demonstrated that liraglutide and insulin were the most effective of
the four medications in keeping A1C levels less than 7%. Glimepiride had a smaller
effect and sitagliptin showed the lowest effect, resulting in the highest frequency of
developing A1C levels greater than 7%. Insulin glargine was most effective in keeping
A1C levels less than 7.5%, a secondary outcome of the study. The results were similar among

men and women and across the different races and ethnicities and age
groups.

Additional findings include:

• Weight loss: On average, participants treated with liraglutide and sitagliptin
had more weight loss than those treated with glimepiride, while the participants
assigned to insulin glargine had stable weight over time.
• Side effects and risk: Liraglutide had more gastrointestinal side effects, such
as nausea, abdominal pain, and diarrhea, than the other three medications.
Glimepiride was associated with a higher risk for low blood glucose than the
other medications.
• Complication benefits: Based on preliminary results, liraglutide had a relative
benefit compared with the three other medications for reduction of a composite
outcome of heart attacks, stroke, and other heart and vascular complications.

“The ultimate goal of GRADE is to help clinicians select the therapies that will work
best for individual patients, as diabetes care is not a one-size-fits all approach,” said
David M. Nathan, MD, Director, Diabetes Center, Massachusetts General Hospital,
Professor of Medicine, Harvard Medical School, Boston, MA and lead study chair.
“We believe these results will provide value to both patients and their providers when
deciding which medication is needed to meet their appropriate blood glucose target and
we are encouraged that these findings can be applied to a very diverse range of
patients.”

“Comparative effectiveness trials like GRADE are essential in helping people make
decisions about how to best manage and treat chronic diseases like type 2 diabetes,”
said Dr. Henry Burch, NIDDK project scientist for the study. “NIH supports GRADE and
studies like it to help people with type 2 diabetes make informed choices between
medications based on individual patient needs and the characteristics of the
medications.”

The authors state that future analyses of the results from the highly diverse GRADE
participants will help personalize the use of glucose-lowering medications in type 2
diabetes.

Research presentation details:

• Dr. Nathan and study investigators presented the findings of the trial during the
symposium listed below.
o Results of the Glycemia Reduction Approaches in Diabetes—A Comparative
Effectiveness (GRADE) Study (includes live video Q&A period)
o Date: Monday, June 28, 4:30–6:55 p.m. ET (all sessions will be recorded
and accessible for 90 days)

About the ADA’s Scientific Sessions

The ADA’s 81st Scientific Sessions, the world’s largest scientific meeting focused on
diabetes research, prevention and care, will be held virtually June 25-29, 2021. Leading
physicians, scientists and health care professionals from around the world will unveil
cutting-edge research, treatment recommendations and advances toward a cure for
diabetes. Though the conference will be remote this year, attendees will receive
exclusive access to nearly 2,000 original research presentations and take part in
provocative and engaging exchanges with leading diabetes experts. Learn more and
register at scientificsessions.diabetes.org and join the Scientific Sessions conversation
on social media using #ADA2021.

About the American Diabetes Association
Every day more than 4,000 people are newly diagnosed with diabetes in America. More
than 122 million Americans have diabetes or prediabetes and are striving to manage
their lives while living with the disease. The American Diabetes Association (ADA) is the
nation’s leading voluntary health organization fighting to bend the curve on the diabetes
epidemic and help people living with diabetes thrive. For 80 years the ADA has been
driving discovery and research to treat, manage and prevent diabetes, while working
relentlessly for a cure. We help people with diabetes thrive by fighting for their rights
and developing programs, advocacy and education designed to improve their quality of
life. Diabetes has brought us together. What we do next will make us Connected for
Life. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES
(1-800-342-2383). Join the fight with us on Facebook (American Diabetes Association),
Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn).

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