Weight loss treatments have transformed the way we treat obesity. Clinical trials show that people using these medications can lose anywhere between 16% and 21% of their body weight, depending on the drug and how well they stick with treatment.1,2 For many, that’s life-changing progress which leads to less breathlessness when walking upstairs, clothes that fit more comfortably, and improved health markers like blood pressure or blood sugar.1-3
But around 10–15% of people in clinical trials lost less than 5% of their body weight – the threshold considered “clinically meaningful.”1,2 In the real world, obesity specialists estimate that as many as 1 in 5 people don’t respond in the way they hoped. That doesn’t mean the medications are “ineffective,” but it highlights that weight loss is deeply individual, and our biology plays a major role in how we respond.
So why do some people see dramatic results, while others struggle? And why might switching from one medication to another help?
How the medications work
These injections mimic the natural hormones your gut produces after you eat. These hormones communicate with your brain to say “you’re full,” slow down digestion, and help regulate blood sugar.
Some treatments act on GLP-1 receptors, which reduce appetite and promote satiety.1
Others also act on GIP receptors, giving a “dual effect” on appetite, energy storage, and insulin response.2
By targeting one or both pathways, the drugs can quieten the hunger signals that usually kick in when you cut calories. Normally, if you diet, your body fights back by increasing appetite and reducing energy burn, a survival mechanism that can make weight loss frustrating.3 These medications switch off that defence system, making lifestyle changes like diet and exercise more effective.
But people aren’t all wired the same way. The gut-brain axis is influenced by genetics, hormones, and even the microbiome.4 In other words, these drugs can affect appetite control in one person in a profound way, while in another, the response is far more modest.
Why don’t some people respond well to certain weight loss medications?
Obesity isn’t a failure of willpower. It’s a complex mix of biology, environment, and lifestyle. For example, research shows that around 0.3% of the UK population carries a genetic variation that disrupts appetite regulation, leading to significant weight gain from childhood.4 For people with differences like this, one type of medication may work brilliantly, while another produces only a small effect.
Even outside of rare mutations, hundreds of genes play a role in appetite, metabolism, and fat storage.6 This variability may help explain why some people fall into the “non-responder” group.
In trials, participants also receive intensive support from dietitians, psychologists, and exercise coaches. That combination boosts results, but in real life, many people don’t have the same level of structured support. Without it, progress may feel slower or stall altogether.
Lifestyle, adherence, and the long game
The science also shows that consistency matters. Clinical trials run for well over a year, with participants monitored closely. Outside that environment, people sometimes stop early, miss doses, or ramp up doses too quickly. This can lead to side effects, reduced effectiveness, or weight regain.
It’s also worth remembering that weight loss injections are intended as long-term treatments. One 2022 study found that people who stopped treatment regained two-thirds of their lost weight within a year.7 For many, this reinforces the idea that obesity is a chronic condition requiring ongoing management, much like high blood pressure or asthma.
Why switching sometimes helps
If one medication isn’t delivering the results you’d hoped for, your clinician might suggest switching. That’s because different drugs target the appetite and energy pathways in slightly different ways.
Dual-action treatments (working on GLP-1 and GIP receptors) may feel stronger for some people, offering more appetite suppression.
GLP-1-only treatments may suit others better, especially if side effects are an issue. Cardiovascular protection is another factor, as one medication in this class has been shown to reduce the risk of heart attack and stroke, which can be an important reason to choose it if you’re at higher risk.
Switching is often seamless, but there may be a small hiccup depending on your circumstances. There typically isn't a washout period when switching between weight loss medications, meaning that there won't be a delay in your treatment if you were to switch. Your prescriber will ensure that you start at the dose of your new treatment that’s safe for you and minimises disruptions to your weight loss journey. They’ll also take into account your current medication dose, side effects, and your personal goals when deciding the most appropriate starting dose
Managing expectations
It’s easy to see headlines about dramatic weight loss and expect the same for yourself. But the reality is more nuanced. These injections are effective for most people, but not all.
If you don’t see big changes at first, it doesn’t mean you’ve failed. It may simply mean your biology responds differently, or that another medication might be a better fit. It could also mean that lifestyle adjustments like sleep, stress, nutrition, and activity need a closer look.
Studies have shown that the best results come when medication is combined with lifestyle changes: eating nourishing foods, staying active, getting enough sleep, managing stress, and having good social support. These habits reinforce the effect of the medication, while also improving overall health in their own right.
The numan take
The arrival of weight loss medications has reshaped what’s possible in obesity care. For millions of people, they represent the first effective option for sustained weight loss. But one size doesn’t fit all. Around 1 in 5 people may not see the results they expect, and that’s where switching, ongoing monitoring, and lifestyle support can make a difference.
These medications are powerful tools, but they’re not magic. If one treatment isn’t the right fit, there are alternatives. With the right plan, switching may be exactly what’s needed to help you keep moving towards your goals.
References
Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4 randomized clinical trial: The STEP 4 randomized clinical trial. JAMA: the journal of the American Medical Association. 2021;325(14): 1414–1425.
Ard J, Lee CJ, Gudzune K, Addison B, Lingvay I, Cao D, et al. Weight reduction over time in tirzepatide-treated participants by early weight loss response: Post hoc analysis in SURMOUNT-1. Diabetes, obesity & metabolism. 2025;27(9): 5064–5071.
Sarwan G, Daley SF, Rehman A. Management of weight loss plateau. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025.
Clinical Pharmacist and Copywriter, Master of Pharmacy (MPharm)
Hassan is a specialist clinical pharmacist with a background in digital marketing and business development. He works as a Clinical Copywriter at Numan, leveraging his research and writing abilities to shine a light on the health complications affecting men and women.
