Semaglutide lowered teen BMI by 16 percent in STEP TEENS trial

The New England Journal of Medicine published results from STEP TEENS, a 68-week randomized, double-blind, placebo-controlled trial of semaglutide in adolescents with obesity, on December 15, 2022 ^[1]. Mean body-mass index fell 16.1 percent in participants taking semaglutide 2.4 mg once weekly, while it rose 0.6 percent in those taking placebo ^[1].

The trial enrolled 201 adolescents aged 12 to under 18. To qualify, participants needed a BMI at or above the 95th percentile, or a BMI at or above the 85th percentile plus at least one weight-related coexisting condition. All but one had obesity ^[1]. Participants were assigned in a 2-to-1 ratio to weekly subcutaneous semaglutide at 2.4 mg or placebo, and both groups also received a lifestyle intervention. A total of 180 participants, or 90 percent, completed treatment ^[1].

The primary endpoint was the percentage change in BMI from the start of the trial to week 68. The estimated difference between groups was minus 16.7 percentage points (95 percent confidence interval, -20.3 to -13.2; P<0.001) ^[1].

On the trial's secondary confirmatory endpoint, 95 of 131 participants (73 percent) taking semaglutide lost at least 5 percent of body weight by week 68, compared with 11 of 62 (18 percent) on placebo. The estimated odds ratio was 14.0 (95 percent confidence interval, 6.3 to 31.0; P<0.001) ^[1].

Reductions in body weight and improvements in cardiometabolic risk factors were also greater with semaglutide than placebo, including waist circumference and levels of glycated hemoglobin, lipids other than HDL cholesterol, and alanine aminotransferase ^[1].

Gastrointestinal adverse events were more common with semaglutide, reported in 62 percent of that group versus 42 percent on placebo. Five participants (4 percent) taking semaglutide and none taking placebo developed cholelithiasis, or gallstones. Serious adverse events were reported in 15 of 133 participants (11 percent) on semaglutide and 6 of 67 (9 percent) on placebo ^[1]. The trial was funded by Novo Nordisk, the maker of semaglutide, and registered as NCT04102189 ^[1].

Wegovy is the brand of semaglutide approved for weight reduction. Its label covers adults and pediatric patients aged 12 years and older with obesity, used in combination with a reduced-calorie diet and increased physical activity ^[2]. A pediatric weight-reduction study of Wegovy injection in patients aged 12 and older appears in the label's clinical studies section ^[2].

The label carries a boxed warning that semaglutide causes thyroid C-cell tumors in rodents, that it is unknown whether it causes such tumors including medullary thyroid carcinoma in humans, and that the drug is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2 ^[2]. The most common adverse reactions in adults or pediatric patients aged 12 and older include nausea, diarrhea, vomiting, constipation, abdominal pain, dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and hair loss ^[2]. Acute gallbladder disease has occurred in clinical trials ^[2]. The label states Wegovy may cause fetal harm and, for patients taking it for cardiovascular risk reduction or weight reduction, advises stopping at least two months before a planned pregnancy because of semaglutide's long half-life ^[2].

Why it matters for patients

Before STEP TEENS, the trial's authors noted that semaglutide's 2.4 mg dose was used to treat obesity in adults but had not been assessed in adolescents ^[1]. The results give families and clinicians pediatric randomized data rather than an extrapolation from adult studies.

The comparison matters too: the placebo group received a lifestyle intervention and still gained BMI on average, while the semaglutide group lost substantially ^[1]. But the trial also shows the trade-offs — stomach-related side effects in most participants on the drug, and gallstones in a small number of them ^[1]. Wegovy's label lists similar gastrointestinal effects and a boxed warning that applies regardless of age ^[2].

The trial included a follow-up period after participants stopped taking semaglutide or placebo, according to the published figure descriptions, but results from that period are not described in the abstract ^[1]. Whether the BMI reduction is maintained after treatment stops, and what happens over years rather than 68 weeks, has not been reported in these sources. The trial also did not report outcomes such as diabetes prevention in this population.