Leading medical journal proposes anti-obesity drugs from toddler age for life
No child left behind (in the anti-obesity drug campaign)
It’s no secret that obesity is a huge problem in the United States and most of the developed world. Wegovy, the trade name for the injectable drug semaglutide which assists in weight loss, is proving immensely popular despite the huge price tag, and has been approved for adults and children over the age of 12.
But what about young children?
After all, obesity in early childhood is often a predictor of weight and health problems in later years. According to the CDC (Centers for Disease Control and Prevention), just over 1 in 5 adolescents between the ages of 12 and 19 are obese (22.2 percent), only slightly more than the rate in children between the ages of 6 and 11 (20.7 percent). Even among younger children, almost 13 percent are considered obese.
There are currently no FDA-approved drugs to treat obesity in children under the age of 12, but the FDA is now considering approving not Wegovy but a similar drug, liraglutide, which has been around for over a decade.
Liraglutide was first approved in 2010 for improving blood sugar levels in people with type 2 diabetes. Four years later, it was approved for weight loss as well. Like Wegovy, it is associated with a long list of unpleasant side effects; unlike Wegovy, it does not appear to be linked with the development of psychiatric (aka emotional) problems or with suicidality. Perhaps this is why the FDA is considering the approval of liraglutide rather than Wegovy (semaglutide) for young children.
Daily drug injections for 6-year-olds...
The trial investigating use of liraglutide in children between the ages of 6 and 12 was published a few weeks ago in the New England Journal of Medicine and conducted by Novo Nordisk, which manufactures Victoza and Saxenda (liraglutide). 82 children participated in the trial, with 56 in the liraglutide group and 26 in the placebo group. Liraglutide is, like Wegovy, taken by injection — unlike Wegovy it must be injected on a daily rather than a weekly basis. The placebo group had inert injections, and both groups had “lifestyle interventions” throughout the trial.
These interventions lasted throughout the trial period (and not the follow-up) and consisted of individualized counseling at every visit by a qualified health care professional to encourage adherence to a healthy diet, as well as a goal of 60 minutes per day of moderate-to-high-intensity physical activity.
The trial lasted for 56 weeks, plus another 26 weeks of follow-up when no injections were given. Children were recruited from nine countries in 23 sites.
Researchers were focused on changes in BMI, but also measured percentage change in body weight and separately calculated the number of children who experienced a drop of BMI of over 5 percent.
... for a 6-percent drop in BMI
At the end of the 56 weeks, there were clear though small differences between the liraglutide and placebo groups. Those children who received the drug had on average seen their BMI drop by 5.8 percent; those in the placebo group had seen their BMI increase by an average of 1.6 percent.
In the drug group, the average percentage change in body weight was 1.6 percent (that is, they gained weight); in the placebo group, this was significantly higher, at 10 percent.
Almost half of the children who took the drug (46 percent) saw their BMI drop by at least 5 percent (despite their weight gain as they grew taller). In the placebo group, only 9 percent of children had their BMI drop by at least that amount.
Serious side effects for over 1 in 10 children
Almost all of the children experienced unpleasant side effects during the trial, including those in the placebo group. The nature of these adverse events is not described aside from categorization of some of them as “gastrointestinal,” (mostly nausea, vomiting, and diarrhea). Most gastrointestinal side effects occurred in the drug group, in which 80 percent of children experienced them; in the placebo group, only 54 percent did.
There was a marked difference in the incidence of serious adverse events in the trial. 7 children (12 percent) of the drug group had a serious adverse event and for 6 of those 7 children, it was serious enough that they withdrew from the trial. These included two cases of vomiting and one of colitis for which emergency care was required. By contrast, only 2 children in the placebo group had a serious adverse event. In both cases, it was not grave enough for them to require emergency care or to withdraw from the trial.
No one died during the course of the trial or the follow-up period.
Since nothing else helps, try this just the same...
The conclusion drawn by the researchers was that,
Among children (6 to <12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions.
They stressed the importance of having a drug option for assisting with weight loss, given the many illnesses and conditions which result from obesity:
Childhood obesity, which is a predictor of adolescent obesity and often persists into adulthood, is associated with serious, lifelong complications, including type 2 diabetes, metabolic dysfunction–associated steatohepatitis, many cancers, and an increased risk of death from cardiovascular disease in adulthood.
And they noted correctly that lifestyle interventions alone are often either ineffective or not sufficiently effective in making a real difference for obese children:
Lifestyle interventions that support a healthy diet and regular physical activity are the cornerstones of treatment of obesity in children and adolescents; however, the sustained effect of these interventions on the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) is modest.
... even though most kids carry on eating regardless
Drugs such as Wegovy and liraglutide are known as GLP-1 analogues which give the feeling of being full, leading some people to stop eating. They also reduce appetite, slow down the rate at which the stomach empties, and make eating less emotionally rewarding, it is believed, by acting on certain neurotransmitters.
Nonetheless, it was clear from the trial results that merely tricking the brain into believing that no more food was needed or desired had very limited results. The changes in BMI were very modest in the drug group throughout the 56 weeks of the trial; moreover, over the next 26 weeks of follow-up, when the drug was no longer being injected, BMI went up again.
At 82 weeks, when follow-up ended, children in the liraglutide group had a drop of BMI on average of just 0.8 percent (i.e., it had increased by 5.9 percent throughout the 26 weeks after the drug was stopped). In the placebo group, the children’s average BMI was 6.7 percent higher than it had been at baseline, an increase of 4.6 percent from the end of the trial.
Will 'stunting' weight also lead to stunted development?
Looking at changes in weight rather than BMI, those in the drug group saw their weight increase by 9.9 percent between the end of the trial and the end of follow-up; those in the placebo group saw their weight increase by 8.8 percent over the same period.
This translated into an increase in weight of 1.1 kg over the 82 weeks in the drug group, and 7.1 kg in the placebo group.
Other health indicators showed modest differences between the groups. For example, blood pressure in the placebo group was 3.4 mm Hg higher than that in the drug group, on average.
The researchers also examined changes in height, height standard-deviation score, bone age, and pubertal status (Tanner stage 1, 2 or 3, and 4 or 5) from baseline and found them to be similar in the two groups at week 56. Nonetheless, some professionals have voiced concern regarding drugs that suppress appetite in growing children, as Dr. Simon Cork, Senior Lecturer in Physiology, Anglia Ruskin University, noted:
Developing anti-obesity medication for use in children is complicated by the fact that children are actively growing, and therefore there is a possibility for greater risk, particularly with regards to appetite suppression, since such medications have the potential to stunt growth.
Another contentious issue is how valid a criterion BMI is when applied to children. There is no medical consensus on what a “clinically meaningful change in BMI in children and adolescence might look like,” notes Professor Astbury of the University of Oxford’s Diet & Obesity Department. Therefore, assessing the efficacy of a treatment is by no means simple among a population of growing children.
To be approved?
Whether or not the FDA decides to approve liraglutide remains to be seen. The American Academy of Pediatrics, meanwhile, has already added a recommendation to offer drugs to counter obesity to its Clinical Practice Guidelines, for children over the age of 12, adding that one “may offer children ages 8 through 11 years of age with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment.”
The study’s researchers noted that a number of limitations related to the study, including a lack of long-term safety data and of data on bone mineral density. Meanwhile, the study has continued in an open-label phase, with children receiving daily injections and being monitored; this will continue until 2027.
Obesity a disease without a cure...
Commenting on the fact that most children seemed to “relapse” into obesity after being taken off liraglutide, the study’s authors said that this offered proof that obesity is a “chronic disease”:
Among children and adolescents, an increase in BMI occurred after discontinuation of pharmacotherapy, which supports the evidence that obesity is a chronic, relapsing disease.
They made no comment on the eating habits of the children in the study, the extent to which they overeat or to which they eat unhealthy food and whether there were any enduring changes in their eating habits in the follow up period, leaving open the possibility that drugs alone may not provide a long term solution to obesity.
... which must therefore be 'managed' for life
What the study’s authors did note was that a large German trial following over 50,000 very young children found that “almost 90 percent of children with obesity at 3 years of age were overweight or obese in adolescence. The investigators concluded that among adolescents with obesity, the most rapid weight gain had occurred between 2 and 6 years of age.
They concluded from this that drug treatment for obesity should start young and continue, and continue:
Therefore, clinical management of obesity should consider the most appropriate timing for treatment initiation and continue throughout life.
The information contained in this article is for educational and information purposes only and is not intended as health, medical, financial or legal advice. Always consult a physician, lawyer or other qualified professional regarding any questions you may have about a medical condition, health objectives or legal or financial issues.
