A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically significant 5% loss in weight for roughly two thirds of sufferers with each obese/obesity and type 2 diabetes, researchers report.
These findings from the Semaglutide Therapy Impact in Individuals With Weight problems 2 (STEP 2) trial, one in every of 4 part 3 trials of this drug, which is presently below regulatory evaluate for weight reduction, had been published March 2 in The Lancet.
Greater than 1000 sufferers (imply preliminary weight, 100 kg [220 lb]) had been randomly assigned to obtain a life-style intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they’d misplaced a imply of 9.6%, 7.0%, and three.4%, respectively, of their beginning weight.
As well as, 69% of sufferers who had acquired semaglutide 2.4 mg skilled a clinically significant 5% lack of weight, in contrast with 57% of sufferers who had acquired the decrease dose and 29% of sufferers who had acquired placebo.
The upper dose of semaglutide was related to a larger enchancment in cardiometabolic danger elements. The security profile was much like that seen with different medicine on this class.
“By Far the Finest Outcomes With Any Weight Loss Drugs in Diabetes”
Importantly, “greater than 1 / 4 of members misplaced over 15% of their physique weight,” senior creator Ildiko Lingvay, MD, pressured. This “is by far the very best end result we had with any weight reduction medication in sufferers with diabetes,” stated Lingvay, from the College of Texas Southwestern Medical Heart, Dallas, Texas, in a press release from that college.
“The drug works by suppressing urge for food facilities within the mind to scale back caloric consumption,” she defined. “The treatment regularly tells the physique that you simply simply ate, you are full.”
Equally, lead creator Melanie Davies, MD, stated that the STEP 2 outcomes “are thrilling and symbolize a brand new period in weight administration in folks with kind 2 diabetes.
“They mark an actual paradigm shift in our means to deal with weight problems,” with outcomes nearer to these achieved with bariatric surgery, stated Davies, from the College of Leicester, Leicester, United Kingdom, in a press release from her establishment.
“It’s actually encouraging,” she continued, “that together with the burden loss we noticed actual enhancements on the whole well being, with vital enchancment in bodily functioning scores, blood stress and blood glucose management.”
Lingvay famous that on common, sufferers within the 4 STEP medical trials misplaced 10% to 17% of their physique weight, “which is a big step ahead in contrast with all different drugs presently obtainable to deal with weight problems.” She pressured that these outcomes are comparble to the 20% to 30% weight reduction seen with bariatric surgical procedure.
One in every of 4 Trials Beneath Overview
Greater than 90% of individuals with kind 2 diabetes are obese or have weight problems, and greater than 20% of individuals with weight problems have diabetes, Davies and colleagues write.
Semaglutide (Ozempic), adminstered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is accredited by the US Meals and Drug Administration (FDA) for the therapy of kind 2 diabetes. Dosing research indicated that it’s related to weight reduction.
As beforehand reported, 4 trials of using semaglutide for weight reduction (STEP 1, 2, 3, and 4) have been accomplished. The mixed knowledge had been submitted to the FDA on December 4, 2020 (a choice is predicted inside 6 months) and to the European Medicines Company on December 18, 2020.
The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs placebo had been lately printed. The STEP 1 trial concerned 1961 with weight problems or obese; the STEP 3 trial, 611 adults with weight problems or obese. In every of the trials, some sufferers additionally underwent an intensive way of life intervention, and a few didn’t. In each trials, sufferers with kind 2 diabetes had been excluded.
Topline outcomes from STEP 2 had been reported in June 2020.
STEP 2 Enrolled Sufferers With Kind 2 Diabetes
STEP 2 concerned 1210 adults in 149 outpatient clinics in 12 international locations in Europe, North America, South America, the Center East, South Africa, and Asia. All members had kind 2 diabetes.
For all sufferers, the physique mass index (BMI) was ≥27 kg/m², and the A1c focus was 7% to 10%. The imply BMI was 35.7 kg/m2, and the imply A1c was 8.1%.
The imply age of the sufferers was 55 years, and 51% had been ladies; 62% had been White, 26% had been Asian, 13% had been Hispanic, 8% had been Black, and 4% had been of different ethnicity.
Individuals had been managed with weight-reduction plan and train alone or underwent therapy with a steady dose of as much as three oral glucose-lowering brokers (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for not less than 90 days. They had been then randomly assigned in 1:1:1 ratio to obtain semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.
The beginning dose of semaglutide was 0.25 mg/wk; the dose was escalated each 4 weeks to achieve the goal dose.
All sufferers acquired month-to-month counseling from a dietician about weight-reduction plan (the aim was a 500 calorie/day deficit) and exercise (the aim was 150 min of strolling or stair climbing per week).
The imply A1c dropped by 1.6% and 1.5% within the semaglutide teams and by 0.4% within the placebo group.
Hostile occasions had been extra frequent among the many sufferers who acquired semaglutide (88% and 82%) than within the placebo group (77%).
Gastrointestinal occasions that had been primarily delicate to average in severity had been reported by 64% of sufferers within the 2.4-mg semaglutide group, 58% within the 1.0-mg semaglutide group, and 34% within the placebo group.
Semaglutide is approved in the US as a once-daily oral agent to be used in kind 2 diabetes (Rybelsus) in doses of seven mg and 14 mg to enhance glycemic management together with weight-reduction plan and train. It’s the first GLP-1 agonist obtainable in pill type.
The examine was supported by Novo Nordisk. The authors’ related monetary relationships are listed within the unique article.
Lancet. Printed on-line March 2, 2021. Abstract