Is Phentermine/Topiramate Helpful After Teen Bariatric Surgery?

Marlene Busko

November 15, 2021

In adolescents with obesity who undergo bariatric surgery and have suboptimal weight loss 6 to 12 months later, 12 weeks of phentermine/topiramate therapy may help weight loss, a small pilot study hints.

The researchers randomized 10 adolescents — five to phentermine/topiramate and five to placebo — 6 to 12 months after undergoing sleeve gastrectomy having had suboptimal weight loss.

In the intent-to-treat analysis, body mass index (BMI) in patients who received the regimen dropped on average by 5% and BMI in patients who received placebo increased by 2% (P = .04).

Dr Jaime M. Moore

There were no serious adverse events associated with the medication. However, it was associated with greater mood and behavior side effects and the inability to meet nutrition recommendations due to appetite suppression and early satiety. The researchers noted that the dose of medications can be decreased if such side effects are problematic.

Jaime M. Moore, MD, MPH, assistant professor, Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine, Aurora, presented the findings at ObesityWeek® 2021.

The study showed that "it is feasible to recruit and retain adolescents for an adjunct pharmacotherapy intervention 6-12 months after bariatric surgery," Moore, also a pediatrician at the Children's Hospital Colorado Bariatric Surgery Center, told Medscape Medical News in an email.   

However, due to the small study size, differences in BMI, "should be interpreted with caution," she stressed.

And "we do not yet know what the optimal dose or postoperative timing of phentermine/topiramate (or any other anti-obesity medication) is after bariatric surgery in adolescents to maximize intended effects while minimizing side effects," Moore explained.

She added: "I think it will be important for future studies to incorporate eating cues and behaviors (hunger, fullness, loss of control) to help tailor medication selection (mechanism; single vs combination therapy) and timing of initiation" following suboptimal weight loss after bariatric surgery in adolescents.

Calling Other Centers to Join Forces, Pool Patient Data

Moore said she'd like to see more centers involved in similar research.

"Building on these pilot data, we recognize an important opportunity now for multiple centers specializing in bariatric surgery for youth to join forces and pool our [patient data] to be able to make stronger conclusions about efficacy and safety of anti-obesity pharmacotherapy after bariatric surgery," she observed.

Importantly, "for youth who undergo bariatric surgery, we should anticipate the need to preserve health for decades longer than their adult counterparts," she continued.

"Given the chronic, relapsing nature of obesity as a disease and the known heterogeneity in treatment response, it is critical to better understand the role of adjunct therapies after surgery."

"We fully expect that anti-obesity medications will be one of several important tools in our toolbox to achieve the most favorable long-term outcomes for our [youth] patients."

"Chronic Disease That Requires Lifelong Treatment"

"The biggest takeaway from this pilot [study] is that obesity is a chronic disease that requires lifelong treatment," Elizabeth Parks Prout, MD, who was not involved with the research, told Medscape Medical News in an email.

Moreover, "while bariatric surgery addresses two hormonal pathways of causes of obesity it does not fully address the more than fifteen other pathways," noted Prout, medical director of the Adolescent Bariatric Surgery Program, part of the Healthy Weight Program at Children's Hospital of Philadelphia, Pennsylvania.

"The addition of medications that address additional pathways of obesity seems to be a helpful adjunct to surgery in combination with dietary and exercise changes," added Prout.

In adolescence who undergo bariatric surgery, "some weight regain is normal, about 25%, [which] is typically not weight gain back to baseline, but some weight regain," she noted.

"To that end, in our practice we utilize medication prior to, as well as after, surgery to help address as many pathways as possible in the ongoing treatment of this disease."

Would Postoperative Pharmacotherapy Augment Weight Loss?

Large prospective studies of adolescents in the United States who underwent metabolic surgery report that weight loss after surgery is very variable, and more than half of patients have persistent severe obesity 5 years or more after the surgery despite lifestyle-based standard care, Moore explained.

Moore and her fellow researchers hypothesized that youth with a very high preoperative BMI or suboptimal weight loss after bariatric surgery might have augmented, sustained weight loss if they received postoperative anti-obesity pharmacotherapy.

They chose to study phentermine/topiramate based on safe use of phentermine and topiramate in pediatric patients, a favorable risk–benefit profile of phentermine/topiramate (Qsymia) in adults with weight regain/inadequate weight loss after bariatric surgery, and low out-of-pocket cost of around $25/month. 

They aimed to study 12- to 24-year-olds who had < 26%, 28%, and 32% weight loss at 6, 9, and 12 months postoperatively, or persistent severe obesity 6 months to a year after having bariatric surgery at their center.

Researchers enrolled 10 patients (five in each group), and all patients received ongoing nutrition and physical activity counseling and psychosocial support, as appropriate.

On average, patients were 16.6 years old (range, 14-19), had had surgery 7.5 months earlier, and had lost 20% of their initial weight. Nine patients were female, and six patients had severe obesity (four in the medication group).

There was a wide variation in change in BMI (from –13.0% to +2.9%) in the medication-treated group.

All five patients who received phentermine/topiramate reported experiencing anxiety, irritability, restlessness, difficulty with concentration, and paresthesia at least once.

In conclusion, Moore and coauthors reiterate that multisite safety and efficacy trials "powered to examine differences between adolescents with suboptimal surgical weight loss versus those with expected weight loss, but ongoing severe obesity, are warranted."

The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases. Moore and Prout have reported no relevant financial disclosures.

ObesityWeek® 2021. Symposium. Presented November 5, 2021.

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