An Evidence-Based Guide to 7 Popular Weight Loss Pills and Injections

The medical field is brimming with weight loss medications

With so many products aimed at helping you lose weight, it’s challenging to identify fast weight loss pills that actually work.

In this evidence-based guide, you’ll learn about guaranteed weight loss pills and injections, how each works, their effectiveness and side effects, and more.

What Are Weight Loss Medications?

Weight loss medications are drugs that help you lose weight.

The most common types of weight loss medications are weight loss pills and weight loss injections.

Weight loss medications work in various ways: some help you feel fuller sooner, others curb your appetite or food cravings, and still others make it harder for your body to absorb fat from the food you eat. 

They’re designed to help people who are overweight or obese manage their weight. Therefore, doctors usually only prescribe them if you’re an adult with . . .

• a BMI of 30 or greater
• a BMI of 27 or greater, and you have weight-related health problems such as high blood pressure or type 2 diabetes

Can Weight Loss Medications Replace Diet and Exercise for Weight Loss?

Weight loss medications can’t replace dieting and exercise as a way to lose weight. 

Most research shows that weight loss pills and weight loss injections are only effective when combined with physical activity or healthy eating habits.

If you want a diet and exercise program designed to help you lose fat, build muscle, and get healthy, check out my fitness book for men and women, Bigger Leaner Stronger or Thinner Leaner Stronger.

And if you aren’t sure which training or diet plan is right for you, take the Legion Strength Training Quiz or the Legion Diet Quiz, and in less than a minute, you’ll know how you should eat and train to reach your goals. Check them out here: 

Take the Legion Strength Training Quiz

Take the Legion Strength Diet Quiz

The Best Weight Loss Pills and Injections

1. Orlistat (Xenical or Alli)

What Is Orlistat?: Orlistat is a prescription weight loss pill marketed under the brand name Xenical. 

You can also buy it over the counter under the brand name Alli. The difference is Alli (60 mg) contains a smaller dose of orlistat than Xenical (120 mg).

Both versions of the drug help treat obesity by preventing your body from absorbing the fat you eat. 

How Does Orlistat Work?: Orlistat works by inhibiting the action of lipases, enzymes found in the digestive tract that break down dietary fats into smaller molecules. By blocking these enzymes, orlistat prevents the digestion and absorption of about 30% of the fat you eat, which your body instead eliminates in stools.

Does Orlistat Work: Studies show that orlistat effectively aids weight loss and weight loss maintenance. 

For example, a meta-analysis conducted by scientists at the University of Alberta found that, on average, people who took Alli weight loss pills, exercised regularly, and followed a calorie-controlled diet lost ~3 kilograms more than those who exercised, dieted, and took a placebo.

These studies also show that orlistat significantly improves waist circumference, BMI, blood pressure, blood sugar levels in people with diabetes, and total and LDL (“bad”) cholesterol levels.

Orlistat Side Effects: Despite its effectiveness, Orlistat can cause side effects such as oily stools, fecal urgency, and increased bowel movements.

2. Semaglutide (Ozempic, Wegovy, or Rybelsus)

What Is Semaglutide?: Semaglutide is an injectable medication used to manage obesity and type 2 diabetes, available under the brand names Ozempic, Wegovy, and Rybelsus.

How Does Semaglutide Work?: Semaglutide works by mimicking the action of glucagon-like peptide-1 (GLP-1), a hormone that regulates insulin secretion. When taken in large amounts, it also suppresses your appetite, which can help you eat fewer calories and, thus, lose weight.

Does Semaglutide Work: Studies show that semaglutide enhances weight loss when coupled with a weight loss diet and regular exercise. 

In a 68-week study conducted by scientists at the University of Liverpool, researchers found that people who took semaglutide improved their weight (–34 lb. vs. –6 lb.), waistline measurements (−5.3” vs. −1.6”), blood pressure, blood sugar, cholesterol, and inflammation levels, and physical and mental function significantly more than those who took a placebo.

In other words, semaglutide is almost as effective as bariatric surgery at boosting weight loss and health. 

Semaglutide Side Effects: Most who take semaglutide experience gastrointestinal issues, including nausea, vomiting, stomach pain, diarrhea, and constipation, though these often diminish with continued use. 

And while many experts believe the risks are minimal, some research has linked semaglutide use with an increased risk of thyroid cancer, pancreatitis, diabetic retinopathy, and gallbladder disease.

Another potential side effect of semaglutide is muscle loss. This can occur because semaglutide makes eating undesirable, which can make eating enough protein to maintain muscle challenging.

For instance, in the study by the University of Liverpool, almost 45% of the weight each semaglutide user lost was muscle, and in a study conducted by scientists at the University of Dundee, diabetics taking semaglutide lost ~13 lb. of body weight, of which ~40% was muscle.

This is significant because maintaining muscle is paramount for good health: It decreases your risk of disease, helps you avoid injuries, and boosts longevity. In other words, semaglutide ramps up weight loss, but it does so in a way that’ll likely hinder your health over time. 

3. Phentermine (Adipex-P or Lomaira)

What Is Phentermine?: Phentermine is a weight loss pill used for short-term weight loss in overweight or obese adults and sold under the brand names Adipex-P and Lomaira.

How Does Phentermine Work?: Scientists don’t fully understand the mechanisms by which phentermine curbs appetite. However, most believe it elevates the concentration of norepinephrine, serotonin, and dopamine in your brain.

When these neurotransmitter levels rise, hunger typically recedes. This decrease in hunger encourages you to eat less, lowering your calorie intake, which can facilitate weight loss over time

Does Phentermine Work: Most research shows that phentermine boosts weight loss. On average, people taking phentermine for 3-to-6 months lose ~3-to-7% of their body weight. In other words, if you weigh 200 pounds, you can expect to lose ~10-to-14 pounds within 6 months. 

That said, the effectiveness of phentermine differs between individuals and diminishes over time. As such, doctors often advise people who see little change in body composition after 3 months of taking phentermine to stop. 

While phentermine can aid weight loss, it may give better results when paired with topiramate, a drug primarily used to treat seizures that also suppresses appetite. 

A 2021 meta-analysis showed that people taking phentermine and topiramate lose an average of ~17 pounds more than those taking a placebo. The same study also found that the more you take, the more weight you stand to lose. 

People taking phentermine-topiramate also decreased their waist circumference and improved insulin sensitivity, blood sugar control, and blood pressure. 

Phentermine Side Effects: Commonly reported side effects of phentermine include dry mouth, insomnia, dizziness, palpitations, flushing, fatigue, and constipation.

4. Plenity

What Is Plenity?: Plenity is a prescription weight loss pill. Unlike other weight loss medications that are absorbed into the bloodstream, Plenity functions in the stomach and small intestine.

How Does Plenity Work?: Plenity weight loss pills contain hydrogel particles made from two naturally derived building blocks: cellulose and citric acid. 

Upon ingestion, these particles rapidly absorb water in your stomach, expanding to create a sensation of fullness. This encourages you to consume less food, thereby reducing your calorie intake.

Following a meal, the hydrogel particles continue their journey through the small intestine before being expelled.

Does Plenity Work:  Evidence suggests that coupling Plenity with a calorie-controlled diet and regular exercise can facilitate more weight loss than dieting and exercise alone.

For instance, in a 24-week study published in the journal Obesity (Silver Spring) and funded by Plenity’s creator, Gelesis, researchers found that people who supplemented with Plenity shed an average of 6.4% of their starting weight, compared to 4.4% percent in the placebo group.

Moreover, around 60% of those who took Plenity lost 5% of their weight, with 27% losing at least 10% of their initial weight.

In contrast, within the placebo group, 42% of the participants lost 5% of their starting body weight, and 15% shed 10% or more.

In other words, people who took Plenty were twice as likely to lose 10% of their body weight than those who took a placebo.

Plenity Side Effects: The most common side effects of Plenity include gastrointestinal issues like bloating, gas, and bowel changes. 

However, because Plenity isn’t absorbed into the bloodstream, it’s generally well-tolerated and doesn’t have the systemic side effects common with other weight loss medications.

 5. Liraglutide (Saxenda or Victoza)

What Is Liraglutide?: Liraglutide, marketed under the brand names Saxenda and Victoza, is an injectable medication for managing weight and type 2 diabetes.

How Does Liraglutide Work?: Like semaglutide, liraglutide is a GLP-1 receptor agonist, which means it encourages your pancreas to produce insulin in response to elevated blood sugar levels and helps control appetite by slowing digestion. 

Does Liraglutide Work: When used in conjunction with a calorie-controlled diet and regular exercise, liraglutide can assist overweight or obese people in losing weight and preventing weight regain.

For example, in a study published in JAMA, scientists found that people who followed a weight loss diet and exercise regimen and took liraglutide tended to lose between ~5-to-6% of their body weight. Conversely, those who took a placebo only lost ~2% of their body weight.

Furthermore, up to 54% of people taking liraglutide lost at least 5% of their body weight, compared to only ~21% of people taking a placebo, and up to ~25% of those taking liraglutide lost at least 10% of body weight compared to just ~7% of people taking a placebo. 

Liraglutide Side Effects: Liraglutide may increase your risk of pancreatitis and gallbladder and biliary disease. It may also increase heart rate and cause gastrointestinal symptoms, such as nausea, vomiting, constipation, and diarrhea.

6. Naltrexone Bupropion (Contrave)

What Is Naltrexone Bupropion?: Contrave is a weight loss pill containing two active compounds: naltrexone, an opioid generally used to treat alcohol addiction, and bupropion, a type of antidepressant.

How Does Naltrexone Bupropion Work?: We don’t yet fully understand how Contrave works, though experts believe it affects the brain’s “reward system,” helping you control your food intake and avoid food cravings and overeating.

Does Naltrexone Bupropion Work: Studies show that combining a weight loss diet and exercise with naltrexone and bupropion can enhance weight loss, surpassing the effects of diet and exercise alone.

According to a review by scientists at Boston University School of Medicine & Boston Medical Center, people who followed a calorie-controlled diet, exercised regularly, and took naltrexone and bupropion for a year lost an average of ~11-to-22 pounds.

Naltrexone Bupropion Side Effects: Naltrexone and bupropion may increase heart rate and blood pressure and cause nausea, constipation, headache, vomiting, dizziness, and insomnia.

7. Tirzepatide

What Is Tirzepatide?: Tirzepatide is an injectable medication for treating type 2 diabetes and obesity marketed under the brand name Mounjaro.

How Does Tirzepatide Work?: Tirzepatide works by mimicking the effects of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), two hormones that play a role in managing blood sugar levels, the speed food travels through your digestive system, and appetite. 

Does Tirzepatide Work: Early research has shown promising results for tirzepatide. In one study published in The New England Journal of Medicine, dieters took either a small, moderate, or large dose of tirzepatide or a placebo once weekly for 72 weeks.

At the end of the study, those who took the small dose lost an average of 15% of body weight, those who took the moderate dose lost ~20%, and those who took the large dose lost ~21% of body weight. Conversely, on average, those who took the placebo lost ~3% of body weight. 

Tirzepatide Side Effects: Tirzepatide commonly causes gastrointestinal disturbances, including nausea, diarrhea, and constipation.

FAQ #1: What are the best over-the-counter weight loss pills?

Studies show that when paired with a suitable diet and exercise program aimed at fat loss, Alli weight loss pills can be highly beneficial.

(For a diet and exercise program that effectively aids fat loss, check out my fitness books for men and women, Bigger Leaner Stronger or Thinner Leaner Stronger.)

FAQ #2: How effective are weight loss medications?

All the weight loss medications mentioned above effectively contribute to weight loss. However, to maximize their benefits, you must also follow a diet and exercise program designed to promote fat loss. 

FAQ #3: Are weight loss medications covered by insurance?

Some insurance plans cover weight loss medications.

Contact your insurance provider to determine if your plan includes these medications.

FAQ #4: What is the best injection for weight loss?

Among the GLP-1 agonists (often known as “weight loss injections”), liraglutide (Saxenda) and semaglutide (Wegovy) have received approval for use as weight loss medications.

Both are self-administered injections, with liraglutide taken daily and semaglutide once weekly.

Other GLP-1 agonists for managing type 2 diabetes are occasionally prescribed off-label for weight control. These include:

• Semaglutide (Ozempic or Rybelsus)
• Dulaglutide (Trulicity)
• Liraglutide (Victoza)
• Exenatide (Byetta)
• Exenatide extended-release (Bydureon BCise)
• Tirzepatide (Mounjaro).

FAQ #5: Will I regain weight after I stop taking my weight loss medication?

Most people can expect some degree of weight regain after discontinuing their weight loss medication.

Adopting and maintaining healthy eating behaviors and increasing physical activity can limit the weight you regain or help sustain your weight loss.

To learn how many calories you should eat to continue to lose weight and limit weight regain, check out this article:

How Many Calories Should I Eat?

If you’d like even more specific advice about how many calories, how much of each macronutrient, and which foods you should eat to reach your health and fitness goals, take the Legion Diet Quiz, and in less than a minute, you’ll know exactly what diet is right for you. Click here to check it out.

And to learn how to exercise to improve or maintain your body composition, check out this article:

The Best Way to Lose Weight Fast with Exercise