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Weight loss pills and injections: Do they work?

Robbie Puddick
Written by

Robbie Puddick

Medically reviewed by

Fiona Moncrieff

12 min read
Last updated May 2024

Jump to: Weight loss pills do work, but not without side effects | Weight loss supplements: caution recommended | Weight loss pills and injections | Weight loss supplements | Side effects and safety | Take home message

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Weight loss pills do work, but not without side effects

There’s convincing evidence that weight loss medications can have a positive effect on body mass index (BMI) and weight loss compared to a placebo (a placebo is typically a sugar pill or something similar that looks identical to the drug in the study and is designed to blind the participants from knowing what they’re taking).

The most common weight loss injections and pills are:

  1. Orlistat: Lipase inhibitor. (Brand names: Xenical, Alli)
  2. Liraglutide: GLP-1 receptor agonist. (Brand names: Saxenda)
  3. Semaglutide: GLP-1 receptor agonist. (Brand names: Wegovy, Ozempic, Rybelsus)

These medications all have possible side effects. You must keep this in mind when taking prescription medications and always tell your doctor or healthcare professional if you’re experiencing anything out of the ordinary.

Weight loss pills (or diet pills), injections, and supplements have become more popular as the number of people living with obesity continues to rise globally.

Weight loss is notoriously difficult, and research into effective pharmaceutical interventions has yielded promising results to support people with weight loss.

Weight loss injections, pills, or supplements are used to support people improve their health, reach their weight loss goals, or lose weight before weight loss surgery (like bariatric surgery).

People may often use weight loss drugs alongside a low-calorie diet to support rapid weight loss.

They typically work in one of three ways:

  1. Reducing hunger and appetite: Encouraging you to eat fewer calories.
  2. Reducing the absorption of nutrients: By inhibiting the absorption of energy from the gut, the body will secrete more out of your stool, and you’ll store less fat.
  3. Increasing the amount of fat you burn: This mechanism is less convincing. The idea is that you’ll burn off excess fat stores by burning more fat. Unfortunately, this isn’t always the case, and by burning more fat, you might burn fewer carbohydrates, the total energy you burn might stay the same and weight loss might not occur.

It’s also essential to understand the intention behind weight loss medications.

They’re designed to be taken alongside healthy lifestyle changes to give you a boost and enable you to lose weight, achieve better health, and eventually, come off the medication when ready. Weight loss pills shouldn’t be seen as a lifelong solution.

Suppose you’ve struggled to lose weight over many years; they could boost weight loss as you start to change your lifestyle, and this increase in weight loss early on could provide the motivation to maintain your changes.

However, if you maintain your current lifestyle and habits, you’ll likely regain any weight lost when coming off the medication.

Whilst these medications have been approved in the U.S., UK, and other countries to support weight loss, there’s another side to this story, one where the waters are a tad murkier and far less convincing.

Weight loss supplements: caution recommended

The weight loss industry is estimated to be worth around $200 billion, and companies have jumped at the opportunity to get a slice.

Enter: weight loss supplements.

They’re easy to find and be convinced by their marketing; it’s no surprise that these supplements are on the rise.

While prescription drugs like orlistat, liraglutide, and semaglutide are supported by clinical evidence and approved by drug administrations in the U.S. and the UK, the weight loss supplements industry is unregulated. It’s challenging to know what effect the ingredients used in these supplements will have.

An example is Hydroxycut. Hydroxycut is a brand that produces weight loss supplements, and its products contain green coffee extracts and other known, unknown (or untested) ingredients.

Clinical trials showed promising results on weight loss, but many Hydroxycut products were removed from shelves because of cardiovascular risks and liver toxicity.

Despite this, Hydroxycut products are still commercially available, and reports of liver damage continue to be associated with their use.

Still, some supplements made of natural ingredients have been shown to produce modest weight loss without severe side effects, like green coffee extract.

However, other supplements, such as Garcinia cambogia extract, only seem to induce very modest weight loss (less than 2 kg).

At Second Nature, our clinical research has shown that people lose around 6 kg of weight after six months and, most importantly, keep it off after 12 months or longer.

If you’ve been struggling to lose weight and have tried every pill, supplement, and diet under the sun, Second Nature could be the alternative approach you’ve been looking for.

You’re provided with a registered dietitian or nutritionist for daily support and access to over 400 delicious and nutritious recipes to help you lose weight.

If you’d like to try Second Nature, click here for our weight loss calculator to see how much weight you could lose on our programme.

Otherwise, keep reading as we dig into the science of weight loss pills and their pros and cons.

1) Weight loss pills and injections

The three most common medications that are prescribed or available over-the-counter to support weight management that you’re likely to come across are:

  1. Orlistat: Lipase inhibitor. (Brand names: Xenical, Alli)
  2. Liraglutide: GLP-1 receptor agonist. (Brand names: Saxenda)
  3. Semaglutide: GLP-1 receptor agonist. (Brand names: Wegovy, Ozempic, Rybelsus)

These medications are also used to treat type 2 diabetes as they are effective at lowering blood glucose (sugar) levels and have been shown to improve other risk factors for heart disease, such as high blood pressure.

Weight loss pills: Orlistat (Alli, Xenical)

Orlistat works by inhibiting certain gut enzymes required to break down fat from food. These are called lipases. It’s in a class of drugs known as lipase inhibitors, and research has shown orlistat can support weight loss in individuals living with obesity.

A randomised controlled trial in 539 people living with obesity compared orlistat to a placebo to determine the effect on weight loss maintenance over one year.

The study showed that individuals who lost more than 5% of their weight at 12 weeks lost an average of 8.1% after one year. And individuals taking orlistat were 2.44 times more likely to achieve 5% weight loss compared to placebo.

Similarly, a clinical trial with 237 participants investigated the impact of orlistat in a real-world setting to determine adherence to the medication and whether they were well tolerated.

The results showed that participants lost around 4% of body weight after three months. 80% of participants reported being satisfied with the drug due to its positive effect on weight loss.

However, 56% of individuals reported side effects, with 59.2% being GI issues such as bloating, cramping, and diarrhoea.

Still, only 8.5% of individuals discontinued the use of orlistat due to these side effects, and only two serious adverse events were reported as being associated with the medication.

This suggests that despite the possible side effects, the impact of orlistat on weight loss encourages people to adhere to the medication while making lifestyle changes.

Weight loss injections: Liraglutide and semaglutide

When we eat food, our stomach releases a hormone that helps the body regulate hunger and blood sugar levels. This hormone is called GLP-1 (glucagon-like peptide-1). The actions of GLP-1 are the target of liraglutide and semaglutide.

This class of medications are known as GLP-1 receptor agonists (GLP-1RAs). They essentially mimic the actions of the hormone GLP-1. While having similar modes of action, they have different types of administration:

Liraglutide: Taken once a day.
Semaglutide: Taken once a week.

GLP-1RAs help your pancreas release more insulin to lower blood sugar levels, delay emptying food out of the stomach (also called gastric emptying), and reduce appetite.

Research has suggested that GLP-1RAs are more effective at supporting weight loss than gut lipase-inhibiting drugs like orlistat.

A systematic review and meta-analysis (a study analysing lots of different studies) analysed 28 trials in over 29,000 people investigating the effectiveness of five weight loss medications on weight loss.

The study found that all five medications were more effective than the placebo at supporting weight loss.

This trial included orlistat and the GLP-1-RA liraglutide and found that liraglutide was more effective at weight loss than orlistat and showed that participants were taking Liraglutide were twice as likely to achieve more than 5% weight loss than orlistat.

Semaglutide: more effective than liraglutide and orlistat

A meta-analysis investigated the impact of semaglutide and liraglutide and suggested that semaglutide was more effective for weight loss and lowering blood sugar levels (as measured by HbA1c).

However, the studies used to compare the two drugs were from individual trials, comparing one of the medications with a placebo (a sugar pill). They hadn’t yet been compared directly with one another.

Fortunately, a randomised controlled trial was conducted in 2022 investigating the impact of semaglutide and liraglutide on weight loss in individuals living with obesity.

The results showed that the participants in the semaglutide group lost 15.8% of their body weight compared to 6.4% in the liraglutide group.

Semaglutide was also shown to be more tolerated than liraglutide. 13.5% of participants in the semaglutide group discontinued their treatment due to side effects, compared to 27.6% with liraglutide.

Over 80% of participants in both groups reported GI-related issues such as constipation, cramping, bloating, and diarrhoea.

Due to the positive results from these studies, Semaglutide was made available in 2022 in the UK after the U.S. approved the drug in 2021.

Key points:

  • Orlistat works by restricting the amount of fat absorbed in the gut and promotes weight loss.
  • Common side effects are GI related, such as bloating, cramping, pain, or diarrhoea, but they’re generally well tolerated.
  • Liraglutide and semaglutide are a class of drugs called GLP-1RAs that mimic the hormone GLP-1 by helping to manage blood sugar levels and slow down the release of food from the stomach, reducing appetite and hunger.
  • GLP-1RAs also display side effects, most common being GI related such as cramping, pain, and diarrhoea.
  • Randomised controlled trials have suggested that GLP-1RAs are more effective than orlistat at promoting weight loss.
    Semaglutide is more effective at promoting weight loss than liraglutide and seems to be tolerated better.

2) Weight loss supplements

Medications such as orlistat and the GLP-1RAs must undergo a stringent research and development process before they make it to market. Here’s a brief overview of the research process before a drug can be made available:

  1. Animal trials: Before making it to human trials, drugs must show effectiveness with minimal severe adverse events in animals. Side effects are reported, and the drug can enter human trials if tolerated and appear safe.
  2. Phase I trials: The drug is tested on around 20-100 human participants with varying levels of doses to determine its safety.
  3. Phase II trials: These trials include between 100-300 participants, and the main aim is to determine how effective the drug is in treating a specific disease or condition. They also investigate the most effective dose required to achieve the treatment goal
  4. Phase III trials: Much larger trials in hundreds and sometimes thousands of patients to provide further evidence of the drug’s safety and effectiveness.

Only after going through these phases can a drug make it to market and be made available to the public.

The side effects are listed and made clear to the patients when prescribed, and they often have a maximum use time. For example, semaglutide is only recommended for up to two years.

Unregulated weight loss supplements industry

This stringent process is not followed in the whole weight loss or dietary supplements industry. A manufacturer can effectively use any ingredient they like (as long as it’s not already banned) and take it to market.

Alongside this, there’s no official way of reporting adverse effects that might occur from taking a supplement.

With medication, you can report any side effects to your doctor, and this information can be uploaded to the medical system to keep track of the ongoing rates of side effects from specific drugs. Although, it’s not clear how well this system operates.

As the supplements industry is private and unregulated, this doesn’t occur. It’s very easy for a company to deny that a supplement can cause adverse effects as it could have occurred from something else in the person’s diet or lifestyle, and their intake of the supplement isn’t recorded.

Only when there’s a large wave of side effects reported in the media from certain products are they then withdrawn from the market, as with Hydroxycut.

Are any weight loss supplements safe?

Of course, this isn’t to say that all supplements are potentially harmful; instead, we must apply caution to what we consume.

For example, a meta-analysis showed that green coffee extract can support modest weight loss (around 2.5kg), and none of the studies reported any adverse effects.

However, the authors of this analysis also reported that the studies were poorly designed and executed, so it’s difficult to conclude the effectiveness and safety of green coffee extract.

Suppose you experimented with a weight loss supplement such as green coffee extract, caffeine, Hydroxycut, or Garcinia cambogia extract. In that case, we’d recommend taking note of any side effects you experience and informing your doctor.

You could also find out which companies have an independently verified label, such as Informed Sport which analyses the content of supplements from companies to ensure they don’t contain any illegal or potentially harmful ingredients.

Key points:

  • Prescribed medications must go through a stringent research and development process before being made available to the public.
  • Supplements don’t have to go through this process, and the market is largely unregulated.
  • Hydroxycut is an example of a company that has had to withdraw products due to severe adverse reactions to their weight loss supplements.
  • However, some natural products may be safe and help with weight loss.
  • It’s best to apply caution when taking any supplement and try to buy from reliable sources, like those listed on the Informed Sport website.

3) Side effects and safety

All medications have possible side effects, particularly if you live with other health conditions.

Some will be mild but uncomfortable, such as cramping, and others will be more severe, such as shortness of breath. You must report any side effects you experience to your doctor and healthcare team when on medications.

Interestingly, the medications that may be the most effective at achieving the desired outcome can be the ones that are more likely to cause adverse effects.

A meta-analysis compared the impact of liraglutide and orlistat – as well as three other medications we haven’t reviewed in this guide – on weight loss and the risk of adverse effects.

The results showed that while liraglutide was more effective at supporting weight loss, you were also more likely to discontinue the medication due to the severity of the side effects and adverse events.

Conversely, semaglutide is more effective at supporting weight loss than liraglutide and is better tolerated.

In a randomised controlled trial, 13.5% of participants discontinued their semaglutide medication due to side effects compared to 27.6% of those taking liraglutide.

A rare and severe side effect of liraglutide is the development of thyroid cancer. If you have a family history of thyroid cancer, you shouldn’t take liraglutide.

Generally, weight loss medications are well tolerated and don’t appear to cause severe adverse events in most people.

However, there are examples of drugs being withdrawn from the market as more long-term data comes to light. Lorcaserin was a weight loss drug approved by the Food and Drug Administration (FDA) in the U.S. but was recently withdrawn as data indicated that it increased cancer risk.

The example of lorcaserin is why you must weigh the pros and cons when your doctor prescribes medication or before you purchase it yourself and start treatment. Report any side effects to your healthcare team.

It’s important to note that it’s generally not recommended for women to take weight loss pills, injections, or supplements while they’re looking to get pregnant, are currently pregnant, or breastfeeding.

Key points:

  • All medications will come with a risk of side effects.
    Sometimes, the more effective drugs have a higher risk of experiencing side effects.
  • Generally, weight loss medications are well tolerated and safe.
  • However, there are examples of drugs making it to market only to be removed when more data showed they significantly increased the risk of another disease.
  • Any decision to go on medication should be made with the understanding of the risks and benefits.

Take home message

When entering treatment for any condition, you must weigh the pros and cons and determine whether the ends justify the means.

If you decided to take a weight loss pill to achieve your weight loss goals, you’d likely experience some side effects. They might be tolerable, and they might not.

Randomised controlled trials suggest that the current weight loss medications are generally safe and effective, promoting significant weight loss for up to 12 months.

Particularly semaglutide, which also seems to be tolerated better than liraglutide and other medications.

This weight loss may help you maintain a healthy weight in the long term and outweigh the potential short-term side effects you might experience from the drugs.

But it’s important to understand these medications are designed as short-term interventions.

For the drugs to have health benefits in the long term, you must change your lifestyle to support your health and wellness, like eating a healthy diet based on whole foods, doing more physical activity and regular exercise, supporting your mental health, and getting quality sleep.

Without this lifestyle change, these medications will only provide short-term relief from a complex condition.

Changing your lifestyle is hard, but ironically, the most challenging things you can do in life may actually make your life easier in the long run.

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