Weight loss pills: Everything you need to know

It is a weighty problem. One in eight people across the world now have obesity, leaving them at higher risk of Type 2 diabetes, heart disease, arthritis, fatty liver disease, and certain cancers. In fact, obesity is estimated to cost the NHS around £6.5 billion a year.

Little surprise then that, this May, the health analytics company Airfinity calculated that a record 322 weight-loss medications were currently in development. Of these, injections such as Wegovy have dominated headlines. But that might be about to change. A tablet oral formulation of semaglutide (the active ingredient in Wegovy and the Type 2 diabetes medication Ozempic) is now likely to become available in the next few years.

More regulated oral medications may be in development, but the unregulated market in diet pills is thriving already, often with worrying consequences. In 2022, an investigation by the Pharmaceutical Journal found that social media platforms (and in particular, TikTok) were awash with dangerous advice to take medicines designed for epilepsy, alcohol addiction and migraines as weight-loss pills.

So which legitimate weight-loss pills are on the market, by prescription and over the counter? Do they work, and if so, how and for who?

How they work

Whether taken orally or by injection, all regulated weight-loss and weight-management medications work in one of two ways, explains Prof Alex Miras, a consultant in endocrinology at Ulster University: “Either they make you feel less hungry, by working directly on the brain, or they decrease the body’s ability to absorb fat.”

These medicines exist to treat chronic health conditions. On the other end of the spectrum, “over-the-counter” pills and supplements are designed to help you shed a few pounds. These claim to work in myriad different ways but “they have not been approved formally for weight loss,” says Prof Miras. “So they’re safe, but the data on their efficacy is weak.”

Weight loss pills available on prescription

Orlistat: What is it and how effective is it?

“The only currently available weight-management pills on the NHS are orlistat capsules,” says Tricia Tan, a professor of metabolic medicine and endocrinology at Imperial College London. These have been around a long time, since 1999 in fact, and are taken in tablet form, up to three times a day, before meals.

The pills work by blocking the lipase enzymes that would usually break down the fat you eat into a form your body can absorb.

On orlistat, around 30 per cent of the fat you eat passes through straight through your system instead, leading to weight loss. Still. “The effectiveness is rather limited,” says Prof Miras, “we’re looking at between 3 to 5 per cent weight loss.”

Mysimba: What is it, and how effective is it?

Taken daily, Mysimba is a combination of two active ingredients – naltrexone and bupropion – and, explains Miras, their effect is very different to that of orlistat. “The drug works on the appetite areas of the brain. By reducing your appetite, it reduces your food intake. People eat less, and lose an average of 8 per cent of their body weight after one year.”

Rybelsus: What is it, and how effective is it?

In essence, this is like Wegovy but in pill form, taken daily on an empty stomach with a sip of water (no more than 120ml). Its active ingredient is semaglutide which is designed to suppress your appetite, so you eat less, and it does so by mimicking the action of a gut hormone called GLP-1, which is released after eating and slows down the movement of food in your gut, so you stay full for longer.

However, while Wegovy is prescribed by the NHS for weight management, Rybelsus is not licensed for such and is only available as a treatment for Type 2 diabetes. There are other limitations too. In order for the active ingredients in pills to be absorbed by the gut and have the same effect as an injection, each pill must contain 20-times the dosage.

It must also be taken at least 30 minutes before any food or drink, otherwise it will not be absorbed. “So the only reason to use it, over an injection, is that the idea of swallowing a pill is more palatable to some,” says Prof Miras.

Over-the-counter options

Alli is an over-the-counter version of orlistat, available without a prescription at a dose of 60mg instead of 120mg.

The manufacturers claim you can lose “more than two inches” (or 10 to 15 per cent of your belly fat) from your waist after 24 weeks of use. Overall, however, Prof Tan describes it as “only modestly effective”.

“There are various other over-the-counter pills available such as Garcina cambodgia, raspberry ketones, caffeine and green tea extract,” she adds. But “generally speaking the scientific evidence for these pills is not too strong, and the effects not large”.

Garcina cambodgia, derived from the tropical fruit of the same name, contains the active ingredient hydroxycitric acid, believed to make you less hungry and produce less fat. The jury’s out, however. One large study did not find any difference in weight loss between subjects taking garcinia cambogia and those in a placebo group.

Raspberry ketone is the natural compound that gives the fruit their scent, although the stuff found in supplements is a synthetic version. In some studies on rodents, they appear to have aided weight-management, but in dosages far higher than those available (or advisable) to humans.

Caffeine works by raising the levels of epinephrine (or adrenaline) in your blood, prompting the release of fatty acids from your fat tissue. It increases your resting metabolic rate, and thus the number of calories you burn.

One study suggested that caffeine increased fat burning by up to 29 per cent in lean people, but only about 10 per cent among those who have obesity. However, the more you drink, the more your tolerance can rise, rendering it less effective as a weight-management tool.

Green tea, on the other hand, contains caffeine too but also the powerful antioxidant EGCG, which can help boost your metabolic rate, especially when paired with caffeine. A number of studies suggest green tea extract boosts fat-burning, and while the overall effect is not huge, a significant proportion of the fat lost appears to be composed of visceral belly fat (the most harmful to your health).

What to consider before taking weight loss pills

Will my GP prescribe it for me?

To have orlistat prescribed by an NHS GP: “You’d need to have a body mass index of over 30, or of 28 with an obesity-related healthy complication like Type 2 diabetes, hypertension or high cholesterol, for example,” explains Prof Miras. No-one in the NHS can prescribe Mysimba, principally because it does not meet the National Institute for Health and Care Excellence (NICE) standards for cost-effectiveness. For that, you would need to see a private doctor. You can talk to your NHS GP about Rybelsus if, and only if, you have Type 2 diabetes.

Are there conditions in which I shouldn’t take them?

Yes. “You should avoid Mysimba in uncontrolled high blood pressure, epilepsy, people taking morphine-type pain killers and specific anti-depressants,” says Prof Miras. “While people taking cyclosporine for kidney disease should not take orlistat.”

Safety and side effects

Orlistat is a very safe medication, says Prof Miras, but be warned: “If people eat fat while taking it, they get terrible diarrhoea. Effectively, it works by punishing people every time they eat fat, so that they reduce the amount they consume.”

Mysimba is also very safe, though its side effects include “nausea, constipation, dizziness and vomiting,” lists Prof Tan. Plus, “it can cause insomnia, irritability, and sometimes, not commonly, increases in blood pressure,” adds Prof Miras. For those reasons, it has a relatively high discontinuation rate of 20 per cent, he points out.

The potential side effects of Rybelsus include nausea, stomach pains, diarrhoea, vomiting and constipation.

If they do work, and you can tolerate them, you are also signing up to a lengthy relationship with them. “If they are effective, you take them long term,” summarises Prof Miras.

When it comes to over-the-counter pills: “the preparations that contain caffeine carry the risk of causing heart problems, if taken in large doses and combined with other caffeine-containing products such as coffee or energy drinks,” warns Prof Tan.

“Before buying or taking any type of weight-loss supplement, people should chat it through first with their doctor, pharmacist or nurse about any potential health implications or contraindications,” agrees Nichola Ludlam-Raine, a specialist dietitian and author of forthcoming book How Not to Eat Ultra-Processed. “Because of a potential for medication interaction, some medical conditions or prescription medications may mean that a certain herbal supplement or other over-the-counter preparation is not suitable and could even be dangerous.”

Complimentary approaches to weight loss

“For orlistat, the only lifestyle change you need to make, in order for it to work, is to cut down dramatically on the amount of fat you eat,” says Prof Miras. Because it works on the brain, leaving you wanting to eat less, the efficacy of Mysimba is less dependent on your lifestyle choices. Still, in both cases: “We advise that people improve the quality of the food they are eating, and also to engage in physical exercise, to enhance the weight loss from the medication.”

A Swedish study published in 2004, followed 3,305 people with obesity, for four years. One group took 120g of orlistat three times a day, the other group took a placebo. In year one, the orlistat group shed an average 10.6 kg, compared to the placebo group’s 6.2 kg. That said, both groups also had to eat a calorie-restricted diet, and take daily walks of at least a kilometre in length to achieve those losses. In the end, the researchers concluded that “orlistat plus lifestyle changes significantly reduced the incidence of Type 2 diabetes over four years and improved weight loss”.

“All these interventions should indeed be conducted in conjunction with a low-calorie diet, or other diet restrictions, and exercise,” summarises Prof Tan. “This should be supervised ideally by a registered dietician, to ensure that people do not experience nutritional deficiencies.”

If you’re tempted by the over-the-counter route, do buy from reputable brands and reliable sources, after speaking to a pharmacist or other healthcare professionals, says Ludlam-Raine. You may not even need the pills, once you have made the lifestyle tweaks.

“People may be able to save money by making a few simple adjustments first, before turning to pills and potions,” she says. “It could be as simple as trying to get more sleep, so that they feel better able to make more helpful food choices the following day – for example having the energy to make a healthy salad or sandwich for lunch, instead of relying on a motorway meal deal!”