Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

• Status: Not yet recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Minnesota
• Treatments: Liraglutide; Phentermine; Topiramate

Criteria

Inclusion Criteria:

• Ages 12 to
• Obesity (BMI >/= the 95th percentile for age and sex)

• HgbA1c >/= 6.5% at type 2 diabetes diagnosis

• Negative diabetes auto-antibodies

• No history of pancreatitis

• No family or personal history of Multiple Endocrine Neoplasia-1 (MEN-1)

• No family or personal history of thyroid cancer

Exclusion Criteria:

• Pregnancy or lactation

• Newly-initiated or change in dose of weight altering medication within past 6 months

• Current use of phentermine or topiramate for weight loss

• Current use or previous (within 12 months) use of glucagon-like peptide-1 receptor agonist (GLP-1 RA)

• Current or prior use of dipeptidyl peptidase-4 inhibitors (DPP-Ivi) within 12 months

• Current use of sulfonylureas

• Non-English or Spanish speaking participants