Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity
Status:
Not yet recruiting
Trial end date:
2025-06-01
Target enrollment:
Participant gender:
Summary
As the prevalence of obesity rises in the U.S., so does the incidence of pediatric type 2
diabetes (T2D), which is associated with more aggressive disease progression than in adults.
From 2002-2012, the incidence of T2D in youth increased by 7% annually in the U.S. Compared
to adults. T2D in adolescents is a much more progressive and recalcitrant disease,
characterized by more rapid deterioration of β-cell function and earlier incidence of
exogenous insulin dependence and diabetes-related comorbidities. A potential factor that
drives the rapid progression of adolescent T2D is obesity (body mass index [BMI] >95th
percentile. Effective and safe treatments targeting both obesity and β-cell dysfunction are
needed for pediatric T2D.
In 2012, the FDA approved the use of Phentermine/Topiramate for the treatment of obesity in
adults. This orally-administered medication is available in mid- (phentermine 7.5 mg;
topiramate 46 mg) and high- (phentermine 15 mg; topiramate 92 mg) doses, administered once
per day. In a meta-analysis, phentermine/topiramate was shown to be one of the most effective
obesity medication currently available. A large dose-ranging trial in adults evaluating
phentermine and topiramate as monotherapies vs. phentermine/topiramate demonstrated superior
efficacy of the combination with an acceptable safety profile.
Results from a large phase III clinical trial demonstrated placebo-subtracted weight loss of
>9% with treatment for one year at the top dose. Importantly, a separate trial demonstrated
that the treatment effect is durable out to at least two years.41 The most common side
effects in these trials were paresthesia, dizziness, dysgeusia, insomnia, constipation, and
dry mouth. Improvements were noted in blood pressure, lipids, glucose, insulin, HOMA-IR,
C-reactive protein, and adiponectin.