Are weight loss drugs worthwhile?

Dr Nick Fuller
Leading Obesity Expert at the University of Sydney and founder of Interval Weight Loss.

Over-the-counter (OTC) weight loss pills and prescription weight loss drugs are very appealing for those needing to lose weight. 

Recent data shows that 15% of people have tried an OTC weight loss pill. However, despite the abundance of supplements available, marketed with the promise they can help people lose weight, few have scientific support for their safety and efficacy and they’re often pulled from the market. Of great concern, clinical evidence for the safety and effectiveness of a weight loss supplement is not required before it hits the market.

On the other hand, pharmaceutical prescription drugs require regulatory approval and go through an extensive process to validate their safety and effectiveness. They require a script from the doctor to use.

Two of the latest weight loss drugs approved by overseas regulators, accompanied by significant media attention, are semaglutide and tirzepatide, injectable weight loss that are analogues of gut hormones. They’ve been labelled 'miracle drugs' and 'game-changers', helping people with overweight and obesity lose substantial amounts of weight and keep it off while taking the drug. 

But are weight loss injections safe and as effective as social media suggests?  

What are semaglutide and tirzepatide and how do they work?

Semaglutide (manufactured by Novo Nordisk) is a drug that mimics a hormone called glucagon-like peptide-1 (GLP-1). GLP-1 is produced in our small intestine after eating, acting on appetite receptors in our brain to tell us when we are full. Naturally produced GLP-1 is short-lived and contributes to our feelings of hunger between meals.

GLP-1 stimulates insulin secretion if blood glucose levels are elevated. Hence, semaglutide was developed as a treatment for reducing blood glucose levels in people with type 2 diabetes. This drug stimulates the pancreas to secrete insulin if blood glucose levels are high. It also slows the release of food from the stomach to the small intestine, and this may augment its glucose lowering effects. 

Tirzepatide (manufactured by Eli Lilly) is similar but it combines a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (another hormone that stimulates insulin production) and GLP-1 receptor agonist in a single molecule.

When the appetite lowering effects of semaglutide and tirzepatide were discovered, further trials were done to test their value as weight-loss medications. As a result, semaglutide has been approved for the management of obesity in many countries. In Australia, semaglutide (sold under the brand names Ozempic and Wegovy) is approved as a treatment for type 2 diabetes, and obesity. However, there are current global supply issues. Novo Nordisk have informed the TGA that semaglutide will not be available in Australia from mid-November 2022 until the end of 2023. Tirzepatide (sold under the brand name Mounjaro) has so far only been approved for the management of type 2 diabetes in the United States.

Do they work?

The pros

1. It results in large weight loss while on the drug

There is no doubt semaglutide and tirzepatide have helped people achieve large weight loss when taking the drug.

In trials on people with overweight and obesity, based on their Body Mass Index (BMI), participants who injected semaglutide once weekly reduced their body weight by an average 16% over 68 weeks. In contrast, the trial's control group (who received placebo injections) reduced their body weight by a mean of 2%.

Seventy one percent of trial participants injecting semaglutide reduced their baseline body weight by at least 10%. Only 15% of the control group, who relied on lifestyle interventions (diet and exercise) to reduce weight, achieved this measure.

In trials with tirzepatide the results are even more impressive and similar to longer term results (greater than 2 years) seen following bariatric surgery. In a 72 week trial comparing treatment with tirzepatide and placebo, participants on the highest dose of tirzepatide (the same dose as that approved for people with type 2 diabetes in the United States), reduced their weight by an average of 21% over 72 weeks, whereas participants on placebo achieved an average body weight loss of 3%. 

2. It addresses the underlying biology that drives weight regain

An inability to lose weight is not a lack of willpower. 

When our weight loss plateaus, it is because our body's physiological responses are taking protective action to prevent further weight loss. A person ends up regaining the weight they lost because their appetite changes telling them to eat more, to counteract the weight loss. Both semaglutide and tirzepatide fight the body’s appetite changes in response to weight loss by stimulating anti-appetite receptors in the brain, but only while you’re taking them.

The cons

1. Weight regain occurs when the medication is ceased

Trials completed in 2021 found people taking semaglutide for weight-loss regained weight when the weight loss injections stopped. In one follow-up study, people who stopped semaglutide injections had regained two-thirds of their prior weight loss within a year. Similar declines in cardiometabolic parameters, such as blood pressure and blood glucose levels (both of which increased), were also observed. While there is no follow-up weight loss data yet following cessation of tirzepatide, the same results are expected.

2. They have side effects

Most trial participants taking semaglutide experienced nausea, diarrhoea, vomiting or constipation. While this has shown to subside with time, 4.5% ultimately stopped injecting the drug because of these side effects. It is a similar story for tirzepatide with 6.2% of people on the highest tirzepatide dose (15 mg weekly) discontinuing drug due to gastrointestinal side effects.

3. The costs are not yet known

The costs for semaglutide 2.4 mg once weekly (branded Wegovy for weight loss) and tirzepatide 15 mg once weekly in Australia are yet to be finalised. They are very costly overseas. The Pharmaceuticals Benefits Advisory Committee rejected an application for semaglutide 2.4 mg once weekly to be subsidised on the Pharmaceutical Benefits Scheme (PBS). However, the PBS subsidises semaglutide 1 mg once weekly for people with type 2 diabetes and a prescription for semaglutide is about $42.50 AUD for individuals with type 2 diabetes. Without the subsidy, a course of semaglutide 1 mg once weekly (a four-week supply on a private prescription) will cost approximately $135 AUD. While semaglutide is unavailable due to current global supply issues, an older Novo Nordisk GLP1 analogue, liraglutide (Saxenda) is approved for weight loss in Australia. At the recommended dose of 3 mg daily with mean weight loss of 6.4%, it costs approximately $390 AUD per month. 

4. You are required to inject them

Because they are hormone-like proteins, both drugs need to be administered once-weekly by subcutaneous injection. While some people have a fear of injections, the devices are easy to use in a way that is similar to injecting insulin.

Take-home message

These drugs do not offer a quick fix. Changes to lifestyle - diet, exercise and sleep - are still required to achieve the results reported and you will regain the weight when you cease the drug.

About Dr Nick Fuller

Dr Nick Fuller is the founder of Interval Weight Loss and is a leading obesity expert at the University of Sydney with a Ph.D. in Obesity Treatment. Dr Fuller is also the author of three best-selling books and his work been published in top ranked journals in the medical field, including JAMA, Lancet and American Journal of Clinical Nutrition.