Weight Management in Obese Adults

Introduction to Phentermine-Topiramate Extended-Release

Phentermine-topiramate extended-release (ER) is highly effective for weight management in obese adults, producing 7-10% total body weight loss with moderate to large magnitude effects compared to placebo, and should be considered as a first-line pharmacological option for chronic weight management in appropriate candidates 1

The combination of phentermine and topiramate provides synergistic effects, with a 7.5mg/46mg dose achieving average weight loss of 7.8% (approximately 8.1kg) and a 15mg/92mg dose achieving average weight loss of 9.8% (approximately 10.2kg) 1
The average weight loss with a 7.5 mg/46 mg dose is 6.7 kg, and with a 15 mg/92 mg dose is 8.9 kg, as recommended by the American Diabetes Association 2
45-70% of patients achieve a weight loss of ≥5% with this treatment, according to the American Diabetes Association 2
Semaglutide, a GLP-1 receptor agonist, can lead to significant weight loss (approximately 15-20% of body weight) when administered subcutaneously once weekly, with a standard dosing of 2.4 mg weekly (after titration) 3

The FDA has approved phentermine-topiramate extended-release for chronic weight management in adults with a BMI ≥30 kg/m² or a BMI ≥27 kg/m² with at least one weight-related comorbidity 1
The recommended dosage of phentermine-topiramate ER for chronic weight management in adults is to start with 3.75 mg/23 mg once daily for 14 days, increasing to a maintenance dose of 7.5 mg/46 mg daily, and can be escalated to a maximum dose of 15 mg/92 mg if needed, as recommended by the American College of Cardiology and Gastroenterology guidelines 1

Treatment discontinuation due to adverse events occurs in 17.4% of patients on the 15mg/92mg dose versus 8.5% in control groups (RR 2.08) 1
Serious adverse events are relatively rare, occurring in 4.2% of patients compared to 3.5% in control groups 1
Common side effects of topiramate include paresthesias, cognitive impairment, dysgeusia, dizziness, fatigue, insomnia, constipation, and dry mouth, which should be monitored and managed accordingly 4
Serious considerations for topiramate use include metabolic acidosis, risk of kidney stones, and teratogenic effects, which require monitoring of serum bicarbonate, kidney function, and pregnancy testing for women of childbearing potential 4
Semaglutide may cause gastrointestinal effects (nausea, vomiting, diarrhea), potential risk of pancreatitis, and hypoglycemia (particularly in patients with diabetes) 3

Contraindications for the use of this combination include pregnancy or women planning pregnancy (Category X medication), hyperthyroidism, uncontrolled hypertension or active/unstable coronary disease, concurrent use of monoamine oxidase inhibitors, and anxiety or insomnia that may be exacerbated by phentermine 4
Topiramate is also contraindicated in glaucoma, and women of childbearing potential must use effective contraception due to its teratogenic risk, as recommended by the American College of Obstetricians and Gynecologists 1, 4, 5, 6, 3
Patients with liver or renal insufficiency require special caution due to the increased risk of cyanide/thiocyanate toxicity and metabolic acidosis 7

Required monitoring includes:
Treatment with topiramate should be discontinued if weight loss is less than 3% after 12 weeks at moderate doses or less than 5% after 12 weeks at maximum doses, or if side effects become intolerable, as recommended by the FDA 4
Discontinuation of topiramate should be gradual, taking the medication every other day for at least one week, to minimize seizure risk, as recommended by the Gastroenterology guidelines 1
Continuous monitoring of patients is necessary to ensure safety, including regular checks of vital signs, such as blood pressure, heart rate, and respiratory rate, as recommended by the American Diabetes Association 8, 2