Weight loss medications
Diet and exercise modifications are the foundation of any weight loss program.
Unfortunately, most programs report only a small weight loss after 2 years.
Most will regain weight over the long term, at least in part due to compensatory biologic mechanisms.
If lifestyle interventions aren't successful, medical therapy can be considered after hormonal (Cushing's syndrome, hypothyroidism etc) or medication induced weight gain has been carefully ruled out.
Medications are typically initiated in coordination with diet and exercise if the BMI is > 30 kg/m or if the BMI is 27-29.9 kg/m with a weight related comorbidity.
Weight loss medications that I've prescribed include phentermine, orlistat (Xenical), phentermine-topiramate (Qsymia), bupropion-naltrexone (Contrave), liraglutide (Saxenda) and semaglutide (Wegovy).
The goal of any medication regimen is weight loss of >5%.
All of the weight loss numbers listed below are when the medications have been used with lifestyle modifications.
None of the trials included combinations of weight loss medications.
Phentermine is the most commonly prescribed weight loss medication in the United States.
A sympathomimetic amine, schedule IV stimulant, Phentermine is a once daily morning pill that was approved for weight loss in 1959.
Typical doses are 15 mg, 30 mg and 37.5 mg.
Phentermine works predominately via appetite suppression.
The average weight loss in randomized, double-blind, placebo controlled trials is 4%.
Average monthly cost is $35-$40.
The most common side effects, dry mouth and insomnia, tend to wane over time.
Phentermine is the only weight loss medication with FDA approval that is limited to short-term use (12 weeks).
The recommended time before the next treatment of 6 months.
Neither of these time limits are routinely followed, or enforced by pharmacies.
Contraindications include heart disease, uncontrolled high blood pressure, and recent use of MAO inhibitors.
Although I don't prescribe phentermine frequently due to the absence of long-term safety and CV outome trials, it's a relatively effective, inexpensive option with a 60+ year history of use.
Orlistat (tetrahydrolipstatin) is a 3x daily oral medication taken with meals.
It was approved for weight loss in 2007.
It's available via prescription at 120 mg or OTC at 60 mg.
Orlistat reversibly inhibits dietary fat absorption from the gut by ~1/3 at prescription doses.
Inhibition is less with the lower dose OTC formulation.
Average weight loss compared to placebo in randomized double blind trials is 2-4%.
The main side effects are gastrointestinal with 15%-30% of users complaining of fatty stools and/or urgency.
Orlistat may also reduce the absorption of flat-soluble vitamins, especially vitamin D.
Although side effects may be reduced by a low-fat diet (<30% calories from fat), discontinuation rates are high.
Monthly cost varies from $50 to $500 depending on promotions with an average monthly cost of $100.
I rarely use Orlistat due to high cost, unacceptable side effects, three times daily dosing, and lack of efficacy.
Qsymia (phentermine-topiramate ER) was approved for weight loss in 2012.
The most common doses are 7.5 mg phentermine/46 mg topiramate ER (maintenance dose) and 15 mg phentermine/92 mg topiramate ER.
The combination of phentermine and extended release topiramate allows both drugs to be used once daily in the morning at significantly lower doses than when prescribed separately.
Average weight loss in randomized, double-blind placebo controlled trials is 8-11%, depending on the dose used.
80% of users will respond, typically with a 3% weight loss within 6 weeks.
If there is no weight loss after 6 weeks, consideration should be given to discontinuation.
Side effects are dose dependent, transient and mild.
They include dry mouth (most common), insomnia, and change in taste after soda or beer.
Since topimarate has been associated with facial cleft defects in infants exposed in utero, Qsymia should be used with caution in women of child-bearing age. Pre-use pregnancy testing is mandatory.
Discontinuation rates in clinical trials were very low at <5%.
The average monthly cost is $100-$200, although coupons are occasionally available.
Insurance coverage is rare.
Most people achieve adequate weight loss with the 7.5mg/46 mg maintenance dose.
Phentermine and topiramate can be purchased separately as generics for a combined monthly cost of ~$60 or less.
Generic topiramate is not ER, and is typically dosed in the evening.
I prescribe Qsymia frequently due to efficacy, relative low cost, and beneficial side effect profile.
Contrave (naltraxone/buproprion) was approved in 2014.
It's usually well tolerated.
The average weight loss is 3-5% in randomized, double blind placebo controlled tirals.
Monthly costs vary from $100-$400 depending on coupon offers.
Individual components can be purchased as generics with significant cost savings.
The most common side effects are nausea, headaches and constipation.
I rarely prescribe Contrave due to a relative lack of efficacy, high cost and lack of insurance coverage.
Saxenda (liraglutide 3.0 mg) is a GLP-1 agonist that was approved for weight loss in 2014.
It's administered as a once daily SQ injection with a gradual weekly upward titration from 0.6 mg to 3.0 mg.
Average weight loss was 3-6% in randomized, double blind, placebo controlled trials.
The average monthly cost is often >$1000.
There is no generic.
The most common side effects are nausea, diarrhea and constipation.
A slower titration often reduces the severity and frequency of side effects.
I prescribe Saxenda rarely due to exorbitant cost, modest efficacy and consistent lack of insurance coverage.
Wegovy (Semaglutide 2.4 mg) is the most recent GLP-1 agonist approved for weight loss.
It's a once weekly SQ injection delivered via a prefilled pen.
Doses are titrated monthly from 0.25 mg per week to 2.4 mg per week.
Although the average weight loss in randomized, double blind, placebo controlled clinical trials was 6-12%, >30% of participants lost 20% or more.
People without diabetes often respond to lower doses, with many achieving signficant weight loss with the 1 mg pen.
Gastrointestinal events were the most common side effects.
Wegovy is covered by most federal insurance plans.
Without insurance, the average monthly cost in the United States is $1000.
It is a very effective, well tolerated medical weight loss option.
Mounjaro (tirzepatide) is awaiting approval for weight loss.
It is a once weekly SQ injection with agonist activity at both the GLP-1 and GIP receptors.
Doses are titrated up monthly from 2.5 mg to 15 mg per week, as needed.
In people with type 2 diabetes, the 15 mg Mounjaro dose resulted in a 22.5% weight loss.
This degree of weight loss has never been seen before.
Monthly cost without insurance coverage is $500 or more.
Adverse events are most commonly GI with a discontinuation rate in trials of 2.6%-7.1% as doses were increased.
Our center has extensive clinical trial experience with semaglutide and tirzepatide.
Please review any regimen with your physician before beginning therapy.
