“Transformational” semaglutide can cut Type 2 diabetes risk by more than half – University of Alabama at Birmingham

W. Timothy Garvey, M.D.New research presented by University of Alabama at Birmingham researchers shows that a 2.4mg dose of the obesity drug semaglutide can reduce the risk of Type 2 diabetes, or T2D, by 60 percent.
“Semaglutide appears to be the most effective medication to date for treating obesity and is beginning to close the gap with the amount of weight loss following bariatric surgery,” said W. Timothy Garvey, M.D., Butterworth Professor of Medicine in the Department of Nutrition Sciences and lead researcher. “Its approval was based on clinical trial results showing that it reduces weight by over 15 percent on average, when used with a healthy lifestyle program.”
Garvey, who presented at the European Association for the Study of Diabetes in Sweden, added that this amount of weight loss is sufficient to treat or prevent a broad array of obesity complications that impair health and quality of life and is a game-changer in obesity medicine.
According to 2018 data from the National Health and Nutrition Examination Survey, just under half of adults in the United States tried to lose weight in the prior 12 months. Nevertheless, according to CDC data, the obesity rate that year rose to a record 42.4 percent.
UAB’s research teams have been critical to the clinical development of semaglutide, Garvey says.
“We have very good investigators and research professional staff here,” he said. “Our university is playing an important role in the development of these obesity drugs and teaching other physicians about them, and about larger issues of the treatment of obesity through continuing medical education opportunities and then presenting the data at meetings and abstracts and publications and talks.” 
Obesity is known to increase the risk of T2D at least sixfold, and Garvey and colleagues were interested in whether semaglutide could reduce this risk. To learn more, they carried out a new analysis of the data from two trials of semaglutide.
In STEP 1, 1,961 overweight or obese participants received an injection of 2.4mg of semaglutide or a placebo weekly for 68 weeks.  
STEP 4 involved 803 participants with overweight or obesity. All received weekly injections of 2.4mg semaglutide for 20 weeks and either remained on semaglutide or were switched to a placebo for the next 48 weeks.
Participants in both trials received advice on diet and exercise.
The researchers used Cardiometabolic Disease Staging, designed by Garvey and fellow UAB colleagues, to predict the participants’ risk of developing T2D in the next 10 years.
CDMS was previously a highly accurate measure of T2D risk and is calculated using a formula which factors in a patient’s sex, age, race, BMI and blood pressure, as well as blood glucose, HDL cholesterol and triglyceride levels.
Semaglutide, an injectable drug already approved by the Food and Drug Administration as a treatment for T2D, produced moderate weight loss at its dose of 1 milligram weekly. The new trials at UAB and other medical centers around the country, known as STEP, were studying the potential of a higher dose, 2.4mg. The results, released in February 2021, were important enough to warrant prominent placement in the New England Journal of Medicine for the STEP 1 trial results and Journal of the American Medical Association for STEP 3 trial results.
In the STEP 4 participants, the largest decreases in risk scores were seen in the first 20 weeks (from 20.6 percent at week 0 to 11.4 percent at week 20). In those who continued receiving semaglutide, the risk score decreased further to 7.7 percent. But, in those who were switched to placebo, it rose to 15.4 percent.
This indicates that sustained treatment with semaglutide is needed to maintain the reduction in T2D risk.
“Semaglutide reduces the future risk of diabetes by over 60 percent in patients with obesity,” Garvey said. “This figure is similar whether a patient has prediabetes or normal blood sugar levels. Sustained treatment is required to maintain the benefit. Given the rising rates of obesity and diabetes, semaglutide could be used effectively to reduce the burden of these chronic diseases.”

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