Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

Description

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.

Conditions

Pediatric Obesity

Study Overview

Study Details

Study overview

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.

Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

Condition
Pediatric Obesity
Intervention / Treatment

-

Contacts and Locations

Minneapolis

University of Minnesota, Minneapolis, Minnesota, United States, 55414

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Ages 12 to \</= 20 years at study entry
  • * Obesity (BMI \>/= the 95th percentile for age and sex)
  • * HgbA1c \>/= 6.5% at type 2 diabetes diagnosis
  • * Negative diabetes auto-antibodies
  • * English-speaking and Spanish speaking
  • * For participants of child-bearing potential: when sexually active, agreement to use two forms of highly effective contraception (oral contraceptive pill, IUD, implant, and/or condoms) during study participation
  • * Pregnancy or lactation
  • * Newly-initiated or change in dose of weight altering medication within past 6 months, including SGLT-2 inhibitors and DPP-IV inhibitors, liraglutide 1.8 mg and exenatide ER.
  • * Current or recent (\< six months prior to enrollment) use of anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination PHN/TPM, semaglutide, and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion)
  • * Current use of sulfonylureas
  • * Previous metabolic/bariatric surgery
  • * Current use of a stimulant medication
  • * History of glaucoma
  • * Current or recent (\< 14 days) use of monoamine oxidase inhibitor or carbonic anhydrase inhibitors
  • * Known hypersensitivity to sympathomimetic amines
  • * Any history of treatment with growth hormone
  • * any history of bulimia nervosa
  • * Major psychiatric disorder as determined by the local medical monitor
  • * Unstable and clinically-diagnosed (defined as documented in the medical record, if available) depression or PHQ-9 score of \>/= 15
  • * Any history of active suicide attempt, a "yes" answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the "Suicidal Ideation" portion of the C-SSR, or a "yes" to answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS
  • * History of suicidal ideation or self-harm within the previous 30 days or a "yes" answer to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the C-SSRS and the ideation or behavior occurred within the past month.
  • * Current pregnancy or plans to become pregnant during study participation
  • * Current tobacco use
  • * ALT or AST \>/= 3 times the upper limit of normal
  • * Moderate (Child-Pugh score 7-9) or severe (Child-Pugh score 10-15)
  • * Bicarbonate \<18 mmol/L
  • * Moderate (creatinine clearance \[CrCl\] greater than or equal to 30 and less than 50 mL/min) or severe (CrCl less than 30 mL/min) renal impairment
  • * Any history of seizures
  • * HR ≥120 bpm on 3 separate measurements
  • * History of structural heart defect or clinically significant arrhythmia
  • * Diagnosed monogenic obesity
  • * Any history of cholelithiasis
  • * Any history of nephrolithiasis
  • * Clinically diagnosed hyperthyroidism
  • * Untreated thyroid disorder or TSH below the lower laboratory limit of normal
  • * Any disorder, unwillingness, or inability, not covered by any other exclusion criteria, which in the investigator's opinion may put the participant at risk

Ages Eligible for Study

12 Years to 20 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Minnesota,

Megan Bensignor, MD, PRINCIPAL_INVESTIGATOR, University of Minnesota

Study Record Dates

2025-08-01