More Anti-Obesity Drugs for Teens Coming, Devices Are Next Step

Marlene Busko

June 08, 2019

SAN FRANCISCO — Few medical therapies have been approved to treat adolescents with obesity but that is about to change, and a next step will be to test endoscopic devices in teens, two experts have predicted here at the American Diabetes Association (ADA) 2019 Scientific Sessions.

"I think there is a place for medication in adolescent obesity," but current options "continue to remain limited," Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, Louisiana, summarized to Medscape Medical News following his presentation here.

He had explained that only orlistat and phentermine are approved by the US Food and Drug Administration (FDA) to treat adolescents with obesity, whereas nine medical therapies have been approved for weight loss in adults.

"I think that off-label use is going to continue until we have more pediatric adolescent data and we have FDA approvals for [anti-obesity] medications" for adolescents, Hsia predicted.

However, "there is hope on the horizon," he added, "for the specific [obese young] populations that need medical therapy that may not fit so much in bariatric surgery or may not have had quite the benefit from lifestyle modification."

"Liraglutide (Saxenda, Novo Nordisk) [trial] results [in teens] will probably be available early next year," Hsia expects. "That's probably the one that will be the next one up," to be approved for treating adolescents with obesity, he said.

A randomized controlled trial of lorcaserin (Belviq, Eisai) in adolescents with obesity is ongoing and still open for enrolment, he noted, and there is a phase 4 trial that is just starting for phentermine/topiramate (Qsymia, Vivus).

During the same session, Andrew C. Storm, MD, Mayo Clinic, Rochester, Minnesota, summarized the growing number of endoscopic devices that are approved or being tested for weight loss.

The approvals have happened "in the past 3 to 4 years and three to five have FDA approval trials ongoing or starting within the summer [in adults], so I expect to see — if not this year then definitely in the next year or two — quite a number of endoscopic therapies for obesity and metabolic disease available," he told Medscape Medical News.

"It is pretty clear that obesity from childhood carries into adulthood," Storm added. "Given that these [devices] are so safe and have such reasonable impacts in obesity upfront, I think the next step will be studying them in young adults."  

"It's very exciting because there are new and evolving therapies in the field of the treatment of obesity [for adolescents]," session chair Amy E. Rothberg, MD, PhD, University of Michigan, Ann Arbor, told Medscape Medical News.

"It's going to reshape the landscape and practitioners will be more comfortable prescribing these therapies," she predicted.

"Stay tuned, but there are probably going to be double what we have in terms of pharmacotherapy and combination pharmacotherapy in the future" for treating adolescents, she said.

Asked if this will this make a dent in the obesity rate in young people, she replied: "I'm optimistic, so I certainly hope so."

Only Orlistat and Phentermine Approved for Obese Teens

Endocrine Society guidelines published in 2017 (J Clin Endocrinol Metab. 2017;102:709-757) specify that pharmacotherapy with FDA-approved therapies can be suggested for adolescents who are obese if a formal lifestyle modification program fails to limit weight gain or improve comorbidities, Hsia noted.

The guidelines also advise discontinuing therapy if the patient does not achieve a greater than 4% reduction in body mass index (BMI)/BMI z-score by 12 weeks.

Orlistat is the only FDA-approved medication for long-term use in adolescents age 12 years or older, and it is associated with a 0.7 to 1.7 kg/m2 reduction in BMI. However, because of side effects of fecal urgency/incontinence and fatty/oily stools, it is of limited clinical use in this age group.

Phentermine, which suppresses appetite, is approved by the FDA for 12 weeks or less in individuals age 16 years and older. However, it may cause increased blood pressure and heart rate, and there are limited safety and efficacy data in adolescents.

Anti-obesity pharmacotherapies for adults included four drugs approved in the 1950s for short-term use, and the one most commonly still in use is phentermine, Hsia explained.

More recently, in 1999 to 2014, the FDA approved five drugs for long-term use for weight loss: Orlistat (Xenical), lorcaserin (Belviq), phentermine/topiramate (Qsymia), bupropion/naltrexone (Contrave), and liraglutide, a subcutaneous injectable glucagon-like peptide 1 (GLP-1) agonist first approved for type 2 diabetes (as Victoza, Novo Nordisk) but subsequently approved for obesity as Saxenda.

And when used off-label in adolescents, the type 2 diabetes agent metformin decreases BMI by about 1.2 kg/m2 over 6 to 12 months and the GLP-1 agonist exenatide decreases BMI by 1.1 to 1.7 kg/m2 over 3 months.

Similarly, off-label use in adolescents of antiepileptic drugs (topiramate and zonisamide) decreases BMI by about 1.3 to 4.1 kg/m2 over 6 months; growth hormone decreases fat mass in Prader-Willi syndrome; and octreotide may provide weight stabilization in hypothalamic obesity.

Moreover, three drugs approved in adults are currently being investigated in trials in adolescents: lorcaserin (Belviq) 20 mg/day is being studied in a 52-week randomized controlled trial in 12 to 17 year olds; phentermine/topiramate (Qsymia) is being studied in a 56-week phase 4 randomized controlled trial in 12 to 16 year olds; and liraglutide (Saxenda) is being studied in a 56-week trial in 12 to 17 year olds.

And in future, combination pharmacotherapy may come to the fore, as it may allow lower dosing of two drugs with different mechanisms, which might mitigate side effects, Hsia said.

Newer agents in the pipeline include centrally acting agents, gut hormone and incretin targets, leptin analogs, and dual-action GLP-1/glucagon receptor analogs.

Growing Number of Endoscopy Devices

Meanwhile, Storm explained that the number of "devices, techniques, and providers are growing to meet the demand of the obesity pandemic," and there is strong level 1 evidence that endoscopic bariatric therapies can help patients achieve significant weight loss and metabolic improvement.

These devices are safe and cost-effective, and the procedures can be repeated.

FDA-approved intragastric balloons include Orbera, Reshape (a dual balloon system), and Obalon (a gas-filled balloon that is swallowed), which delay gastric emptying and have to be removed after 6 months.

And a pivotal trial is being conducted to obtain FDA approval for an investigational gastric balloon that could stay in place for 12 months, Storm noted.

The FDA has already approved endoscopic sleeve gastroplasty, a type of gastric remodeling that is "probably the most exciting" and "most promising" endoscopic technique, according to Storm, that reshapes the stomach down to the size of a banana, which is similar to bariatric sleeve gastrectomy but uses a minimally invasive procedure.

Another type of gastric remodeling, the primary obesity surgery endolumenal (POSE) procedure, is not yet approved.

Aspiration therapy, on the other hand, has received FDA approval.

And the FDA recently approved Gelesis100 (Plenity, Gelesis) hydrogel capsules, Rothberg added, as previously reported. "We'll see in post-marketing data how that fares," she noted.

"The big question," Storm said, "is how to combine [endoscopic devices] with medication to achieve bariatric surgery levels of weight loss."

ADA 2019 Scientific Sessions. Presented June 7, 2019.

Hsia has reported serving as principal investigator for studies sponsored by Novo Nordisk and Vivus, with funds paid directly to his institution. Storm has reported consulting for GI Dynamics and receiving research support from Boston Scientific.

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