Paired Anti-Obesity Drugs May Help Teens Shed More Weight After Metabolic Surgery

An add-on oral anti-obesity regimen may bolster bariatric surgery-induced weight loss in teens, a researcher reported.

In a pilot study of 10 patients, adolescents who were placed on standard of care plus phentermine (Lomaira, Adipex-P) and topiramate (Trokendi XR, Qudexy XR, and Topamax) saw an average 4.3-point drop in BMI after 12 weeks compared with a 2.3-point gain among those on placebo (P=0.04), according to Jaime Moore, MD, MPH, of the University of Colorado School of Medicine in Aurora.

The prospective, randomized controlled trial (RCT) included youth who had already undergone sleeve gastrectomy, but either continued to have persistent severe obesity 6 to 12 months post-operatively and/or saw less than a 26%, 28%, or 31% weight loss at 6, 9, and 12 months after surgery, respectively, Moore explained in a presentation at the ObesityWeek virtual meeting.

“As far as we’re aware, this is the first pilot RCT of obesity pharmacotherapy among adolescents after bariatric surgery,” she explained. “Initial efficacy data support greater reduction in BMI with phentermine and topiramate versus placebo at 12 weeks.”

Patients in the study had an average age of 16 years. Exclusion criteria were hypothalamic obesity, a history of certain heart conditions, glaucoma, hyperthyroidism, and/or use of other anti-obesity medications within the past 6 months.

A total of five patients were randomized to the active treatment group, while five made up the placebo group. On average, the cohort was about 7.5 months post-operative, yielding an average weight loss of 20%. Nearly all the patients were female.

During the 3-week uptitration phase, active treatment patients were started on a 4 mg dose of phentermine paired with 25 mg of immediate release topiramate. This was subsequently increased to 8 mg phentermine/50 mg topiramate and 12 mg/75 mg. By week 4, the goal dose of 16 mg phentermine/100 mg topiramate was introduced, if tolerated. However, the median maximum tolerated dose was 8 mg/50 mg.

Tolerability proved to be an issue with these patients, as nearly all patients on this combination treatment reported anxiety, irritability, restlessness, difficulty with concentration, mental fogginess, and paresthesia. In comparison, nearly none of the patients on placebo reported any of these adverse events (AEs).

As for serious AEs, significantly more patients on phentermine/topiramate had difficulty meeting nutrition recommendations (60% vs 0% on placebo). Also possibly related to treatment, one participant on active treatment experienced cholelithiasis, while none in the placebo group did.

However, there was no difference between the treatment groups when it came to depressed mood, memory, sleep, rash, fatigue, headache, shortness of breath, chest pain, change in taste, nausea/vomiting, diarrhea, or constipation.

While there was no difference between the groups in terms of systolic or diastolic blood pressure or heart rate, those on active treatment did see a lower bicarbonate level at week 4 of treatment (-4.8 mmol/L from baseline vs -0.6 mmol/L in placebo). However, this appeared to rebound by week 12 (-1.6 mmol/L from baseline vs +1.6 mmol/L in placebo).

“Building on this feasibility data, we really see the necessity for a multisite partnership for these medications and for other medications, including GLP-1 receptor agonists,” Moore explained. However, she noted that although GLP-1 receptor agonists have demonstrated great outcomes in adults, this class of agents haven’t yet been independently tested in an adolescent population. The study abstract states that Moore “may discuss the off-label use of phentermine/topiramate in adolescents post bariatric surgery during this presentation.”

She also noted that “Our high-volume adolescent bariatric surgery centers in the U.S. are performing somewhere before 35 and 50 surgeries per year. And of course, only a fraction of them might benefit from adjunctive pharmacotherapy. So compared to adults, our pool to begin with is significantly smaller.”

Future studies should consider the timing of post-operative pharmacotherapy interventions that impact hunger and fullness, as interventions may need to be more intentionally paired with eating behaviors in order to mitigate nutrition-related concerns, Moore stated.

As for tolerability, it “may be improved by using a single medication versus combination therapy,” Moore acknowledged, adding that both study agents were oral therapies, so injectable options may yield more “predictable” tolerability results.