The idea that instead of the thankless struggle of dieting you might simply take a “weight-loss drug” and watch the stubborn pounds melt away would have seemed impossible just five years ago. Yet now an estimated 1.5 million people in the UK are on GLP-1s, with most seeing miraculous results. These drugs mimic the hormones that regulate blood sugar and appetite. Well-known examples include Ozempic, Wegovy and Mounjaro.
Not only can they fit into their old skinny jeans, if they were unhealthily overweight or had diabetes — which these medications were initially used to treat — their insulin, blood pressure and bad cholesterol levels fall, their blood sugar control improves and their markers of inflammation reduce.
But it’s not all good news. Apart from the drugs’ increasingly prohibitive cost, doctors and patients are flagging up problems with GLP-1s. Most users experience nausea, constipation, uncomfortable fullness, diarrhoea — not “side-effects” but intrinsic to how the drugs work. They affect the gut and brain, slowing stomach emptying and dampening the sense of reward you naturally get from eating — and much else.
• Read more expert advice on healthy living, fitness and wellbeing
“People say your food noise goes down, but so does your sex noise, so does your interest in your vintage motorbike noise,” says Dr Paul Chell, co-author of The Diet Whisperer with his wife Dr Monique Hope-Ross.
Hope-Ross is a former senior surgeon specialising in the management of metabolic eye diseases. She has held clinical and research posts in Dublin, Belfast and Manhattan, and was a clinical adviser to the ombudsman for the NHS. Chell is a former senior surgeon specialising in corneal transplant surgery, and worked as a senior fellow at Moorfields eye hospital in London.
They have treated thousands of patients with metabolic disorders linked to ocular and systemic disease, such as diabetes. Their latest book, entitled Beyond Weight Loss Jabs, is eye-opening. They report — via gastroenterologist friends — that the stomachs of those on GLP-1s often look like rubbish tips, “full of rotting food, sludge and goo”.
“GLP-1 is a very powerful molecule, and no one’s really looked at the long-term consequences of taking it in these doses,” Chell says.
Almost daily, another risk is reported, such as higher incidence of a stroke of the optic nerve. The singer Robbie Williams has attributed his worsening vision to GLP-1s, but a stroke in the nerve — non-arteritic anterior ischemic optic neuropathy — while rare, is serious and irreversible. “It’s a permanent loss of vision,” Hope-Ross says. “It’s total, black, blindness.”
More common is that with zero appetite, some users practically starve themselves and snack on junk food. The former politician Nadine Dorries wrote about losing three stone on Mounjaro and her hair falling out in clumps. She had been subsisting on crisps, a biscuit, half a chocolate bar. “What did it matter?” she had thought. “I was still losing weight.”
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If you care about your health, not just aesthetics, it matters. But first, we need to understand why we’re stuck being fat. When you and your cells are healthy, your body works like a hybrid car. It seamlessly switches between burning two fuels for energy: carbs and fats. “The ideal balance is 60 to 90 per cent fats and 10 to 40 per cent carbs,” Hope-Ross says. “Generally, the fitter we are, the higher our fat-to-carb burn ratio.”
While GLP-1s can be effective in the short term, diet and exercise remain central to long-term health and happiness
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But if we’re significantly overweight, all is not well inside our cells. “Obesity is a sign of poor cellular health,” Chell says. “And when your cells are sick, they are metabolically inflexible.” That means they struggle to burn fat. They predominantly burn carbs. And if you can’t burn fat, you can’t lose weight.
Unsurprisingly, an inability to burn fat makes us carb-dependent, creating a vicious snack-ridden cycle. “If you’re constantly eating carbs — staples like rice, bread, pasta, potatoes and cereal, which break down into glucose — plus foods containing sugar, which break down into glucose and fructose, the cell mechanisms that naturally burn fat become damaged and dormant,” he adds.
That drip-drip-drip of glucose throughout the day repeatedly spikes insulin — which is released by the pancreas to push glucose out of your blood and into cells. When insulin is circulating, you can’t burn fat. Long-term, this pattern leads to insulin resistance and chronic disease.
How do you repair your cells, so they’re healthy, metabolically agile, fit to burn fat as well as carbs? You give them no choice. “You force feed your body fats and cut out the carbs. And it has to then start relearning how to burn fats.”
Chell and Hope-Ross advise a 12-week high-fat low-carb diet. This lowers insulin fast. Within four weeks, the five cellular abnormalities sabotaging fat loss — high insulin is one — start to repair. Once cells start burning fat again, you can turbocharge fat-loss with intermittent fasting. Your cells will obligingly use your belly fat for fuel. As Hope-Ross says, “You’ve got a snack bar round your middle.”
This process is excellent for long-term health. With cells tip-top, you lose inflammatory visceral fat, not muscle. You can start enjoying carbs again. But crucially, because chronic diseases such as arthritis, dementia and diabetes share the same cellular root causes as obesity, by healing your cells, you can reverse, stabilise or prevent many of these conditions too.
But why bother if you can just take GLP-1s? Because its effects aren’t the same. When most people start the jabs, Chell explains, “They haven’t made their cells metabolically flexible.” Meanwhile, their appetite withers. “You lose fuel.”
The body’s response? “I haven’t got fat-burning apparatus working properly. I need carbs.” Chell adds, “It gets carbs by converting amino acids into glucose. The amino acids come from protein. The protein comes from your lean tissue — muscle, ligaments, tendons, bone.”
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So even if you reach your weight-loss goal, Chell says, “It’s fool’s gold. From 15 to 60 per cent of weight loss will be lean tissue.” Hope-Ross says that adding three resistance training sessions weekly for at least 18 months will rebuild it. If not, “You’re in a position of frailty,” she says. You have sped up your muscle loss. “We call it accelerated sarcopenia.” Plus, losing muscle worsens blood sugar control, which leads to raised insulin and eventually weight gain.
Once off GLP-1s, Hope-Ross says, “You’ll struggle to keep that weight off. All your hormones are working against you, because you haven’t changed anything.” Data shows that within a year, “Most people put the bulk of their weight back on, only as fat.”
They suggest that if you plan to take GLP-1s, heal your cells first so they can burn fat. “We believe that that will minimise many of the complications. It will also help to reverse the underlying root causes of obesity so that your metabolism will improve.”
And if you’ve come off the jabs, or don’t wish to take them but want to lose weight healthily, sustainably and reverse disease? Their simple, safe and scientific method is for you too.
The five scientific reasons you’re not losing weight
by Dr Paul Chell and Dr Monique Hope-Ross
1. Fat is trapped in your cells
Any excess glucose you eat, beyond what you can store in your liver and muscles, is converted to fat. Fat is stored as triglycerides in fat globules inside our fat cells. When our body needs energy, these triglycerides must be broken down into fatty acids. The fatty acids must then enter the mitochondria (the power plant of every cell) to be burnt for fuel. In healthy cells, triglycerides can exit the fat globule when needed. In obesity, the “unlocking” mechanism sticks so the triglycerides can’t get out. Your fat is literally locked inside your fat cells so you can’t burn it as energy. More glucose can get in though and is converted to triglycerides, so more and more fat is stored.
2. You have insulin resistance
Insulin is called “the fat-storing hormone” because when it’s in your bloodstream, you can’t burn fat. Anything in your diet or lifestyle that raises insulin levels creates this fat trap. And the higher, longer and more frequently insulin is raised, the worse it gets. Many people are in a high insulin state all day, because they’re constantly consuming carbs and sugars — it’s stealth insulin dosing. Over time, your cells become desensitised to insulin, so it’s released in bigger doses and circulates for longer just to do its job of ushering glucose out of the blood into cells. It’s another vicious cycle — you get high blood sugar that stays high for hours, increasing fat storage, reducing fat burning and making you fatigued.
3. Your mitochondrial drawbridges are up
Theoretically, your mitochondria — the power stations in cells that convert fuel into energy — can burn both carbs and fat. But fats and carbs each get into the mitochondria via their own special “drawbridge”. If your metabolism is healthy, both fat and carbs can get in. But with obesity or poor metabolic health, the fat drawbridge is raised (in scientific terms, carnitine palmitoyltransferase 1 is closed for business). Causes are high insulin, chronic inflammation and oxidative stress, which damages mitochondria, making them less efficient at burning fat. That’s right — not only can fat not escape its fat globule, it can’t get into the mitochondria. So you can only burn glucose. Hello weight gain.
4. Your fat-burning enzymes are faulty
In yet another obstacle to losing weight, the fat-burning machinery inside the mitochondria malfunctions. So even if a doughty triglyceride does make it into the cell’s power plant, the fat-burning enzymes inside are too damaged to process it. Causes include our old nemesis, high insulin. Leptin resistance is also responsible. Leptin is the satiety hormone and when resistance develops, it leads to overeating, plus it directly influences the fat-burning machinery’s ability to burn fat. Being sedentary is also a contributor as there is less demand for fat as fuel. And chronic inflammation also impairs fat burning.
5. You’re high in oxidative stress
A “redox imbalance” essentially means there’s more oxidative stress in your cells than they can overcome with antioxidants and other “reductive” forces. This chemical stress blocks fat burning and fuels inflammation. It leads to mitochondrial dysfunction, faster ageing, low energy and disease. Culprits include chronic stress, poor sleep, pollution, being sedentary and a diet high in UPFs, alcohol and sugary foods.
Nothing is as important as having healthy mitochondria and fit, functioning cells. Follow our rules, and you can.
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