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What’s a Good Weight Loss Pill That Actually Works?

Weight loss pills can help people who are overweight or obese to lose weight. The choice of medication depends on several factors, including a patient's overall health, the presence of any other comorbidities, and more.
Weight loss pills can help people who are overweight or obese to lose weight. The choice of medication depends on several factors, including a patient’s overall health, the presence of any other comorbidities, and more.

Weight loss pills are medications used to treat people who are overweight or obese. All weight loss pills are designed to be used along with healthy eating, exercise, and healthy lifestyle changes.

Patients who are candidates for drug therapy for weight loss include people who have a body mass index (BMI) 30 kg/m2 or greater, or a BMI of 27 to 29.9 kg/m2 with weight-related comorbidities and who have been unable to achieve doctor-prescribed weight-loss goals with lifestyle modifications. 

All the drugs discussed below are proven to reduce weight when taken as directed and combined with diet, exercise, and behavior modifications. 

The choice of medication depends on a patient’s overall health, the presence of any other comorbidities, patient preferences, adverse side effects of each particular drug, and insurance coverage and cost.

Over-the-counter (OTC) dietary supplements marketed for weight loss are generally not recommended due to low-quality evidence or lack of evidence of their effectiveness, and the potential for adverse side effects. Talk to your doctor before taking any over-the-counter supplement for weight loss.

What Are Some Examples of Weight Loss Pills and Their Side Effects?

There are a number of different types of medications used for weight loss that work in different ways. 

Drugs that alter fat digestion include:

  • Orlistat (Alli [available over-the-counter OTC], Xenical [available by prescription]) 
    • Inhibits pancreatic lipases which alters fat digestion so fat is eliminated in feces
    • Can prevent the absorption of about 25% to 30% of calories from fat in the diet
    • May also help with blood sugar regulation, lowering fats, and maintaining blood pressure
    • Considered relatively safe but gastrointestinal side effects are frequently intolerable for patients
    • Side effects of orlistat include:
      • Gastrointestinal cramps
      • Gas (flatulence)
      • Gas with discharge 
      • Inability to control bowel movements (fecal incontinence)
      • Oily spotting 
      • Lowered absorption of fat-soluble vitamins (A, D, E, K) and beta-carotene 
        • A multivitamin is often recommended when taking orlistat 
        • Acute kidney injury 
        • Severe liver injury (rare)

GLP-1 receptor agonists used for weight loss include:

  • Liraglutide (Saxenda, Victoza) 
    • In addition to helping with weight loss, has positive effects on blood sugar
    • The preferred medication for patients with type 2 diabetes, especially those with heart problems
      • Usually used in combination with metformin or another oral diabetes medication for patients with type 2 diabetes, especially when weight loss is an important factor
    • The positive effects of GLP-1 receptor agonists on blood sugar may play a role in how they work for weight loss
    • Slow the movement of food through the stomach which may cause people to feel full more quickly when eating, thus resulting in eating less
    • Side effects of liraglutide include:
  • Semaglutide (Wegovy, Ozempic, Rybelsus)

Combination drugs used for weight loss include:

  • Phentermine-topiramate (extended release) (Qsymia) 
    • Used in men and postmenopausal women with obesity who do not have high blood pressure (hypertension) or coronary heart disease
    • The combination of these drugs boosts weight loss in the first year of use
    • Topiramate increases the risk of birth defects and should be used with caution in women of childbearing potential
    • Side effects of phentermine-topiramate include:
      • Constipation 
      • Dry mouth 
      • Numbness and tingling
      • Anxiety
      • Depression
      • Problems with attention
      • Increased heart rate 
  • Naltrexone-bupropion (sustained release) (Contrave) 
    • Produces similar weight loss similar to orlistat, but has more side effects
    • Not generally not recommended as a first-line drug therapy, but may be used for obese smokers who are seeking drug therapy for smoking cessation and obesity
    • Side effects of naltrexone-bupropion include:
      • Headache 
      • Nausea 
      • Vomiting
      • Constipation 
      • Dry mouth
      • Insomnia
      • Dizziness

Sympathomimetic drugs used for weight loss include:

  • Phentermine (Adipex-P, Lomaira), benzphetamine, phendimetrazine, and diethylpropion
    • Only approved for short-term (12 weeks) use, because they have more side effects and have potential for abuse
    • These drugs are not recommended for use in patients with coronary heart disease, uncontrolled high blood pressure (hypertension), hyperthyroidism, or in patients with a history of drug abuse
    • Side effects of sympathomimetic drugs include:
      • Increased blood pressure 
      • Increased heart rate
      • Nervousness
      • Insomnia
      • Constipation
      • Dry mouth

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References
https://www.uptodate.com/contents/obesity-in-adults-drug-therapy?search=weight%20loss%20pills&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

https://reference.medscape.com/drug/ozempic-rybelsus-wegovy-semaglutide-1000174

https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014