
Weight loss pills could help tackle obesity in poorer countries, experts say
Newly developed weight loss pills could have a big impact on tackling obesity and diabetes in low- and middle-income countries, experts have said.
Weight loss jabs such as Wegovy and Mounjaro, that contain the drugs semaglutide and tirzepatide respectively, have become popular in countries including the UK after trials showed they can help people lose more than 10% of their body weight. Medications containing semaglutide and tirzepatide can also be used to help control diabetes.
However, such jabs are not cheap, require an injection pen and needles, and must be kept refrigerated, limiting their using in low- and middle-income countries (LMICs).
Experts say new oral medications that are expected to be cheaper as well as simpler to transport and store could help tackle a growing health concern in such regions.
'Medicines that could lower diabetes risks and simultaneously reduce risks for heart disease and other obesity-related complications could have sizeable benefits in many LMICs where such disease are starting to escalate fast in part due to rising waist girths,' said Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow.
Dr Louis Aronne, an expert in obesity medicine at Weill Cornell Medical College, agreed. 'What we're going to see is that as we move forward, patients and healthcare providers aren't going to wait for people to develop [complications of obesity] when they can prevent them,' he said.
Aronne's work has shown that when people with obesity and pre-diabetes were given tirzepatide for three years, their risk of developing diabetes fell by more than 90%.
'An oral medicine is easier to distribute since it wouldn't need a cold chain to ensure sterility and activity like the current injectables. It would come in a box or bottle and wouldn't need refrigeration, so could be used anywhere,' Aronne said.
Among the drugs causing excitement is orforglipron, which comes as a daily pill for glucose control and weight loss. Like semaglutide, orforglipron mimics a hormone in the body called GLP-1, helping people to feel fuller for longer as well as increasing insulin production, among other actions.
According to the pharmaceutical firm Eli Lilly, a 40-week phase 3 clinical trial of orforglipron in people with diabetes found the medication reduced blood sugar levels and helped patients shed pounds. Aronne noted that it had a weight loss efficacy in the range of semaglutide.
While semaglutide is already available in pill form, orforglipron has further advantages. Sattar said a much higher dose of semaglutide was required in pill form than is used in jabs to achieve a near similar degree of weight loss, and semaglutide must be taken on an empty stomach and food should not be eaten for half an hour afterwards.
Orforglipron is a small molecule, meaning it is more resistant than semaglutide, a peptide, to being digested in the stomach, and so can be taken alongside food and drink. What's more, orforglipron is unlikely to require as high a dose as oral semaglutide, potentially making it cheaper.
Experts say research is ongoing to test orforglipron for weight loss in people without diabetes and to confirm its safety profile – an important step, not least as Pfizer recently ditched its small molecule GLP-1 drug over a potential drug-induced liver injury.
It is also unclear if orforglipron is associated with a reduced risk of heart attack, stroke or death due to cardiovascular disease, as has been found for semaglutide.
But scientists say that if orforglipron and similar drugs in development reach the market, they could aid efforts to tackle obesity and diabetes, including in LMICs where the prevalence of such conditions is rising rapidly.
Aronne said: 'Better food supply and better diet is definitely something that can prevent obesity, but once it's established, a better diet is not going to treat the majority of people. Something physical changes in the brain that makes it hard for people to lose weight and to comply with the diet, and that's why medication appears to be necessary in this situation.'
Such efforts are also important given the relationship between ethnicity and obesity-related diseases. 'As shown by us and others, south Asians and Blacks – and likely other ethnic groups – are more likely to develop type 2 diabetes at lower weight gains than whites across all ages, so that even small population-wide gains in obesity in many countries will lead to large rises in diabetes,' Aronne said, adding there was even some trial evidence that drugs that mimic GLP-1 may lower risks of heart disease by almost twice as much in Asian people than in white people.
Sattar said: 'The more safe and effective weight loss medicines on the market, both injectable and especially oral, to help tackle rising girths, the better the health of many nations.'
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'I think the other issue is that so far, to my knowledge, the NHS and National Institute for Health and Care Excellence have talked about this being something you take for two years, and that's probably related to data from research studies. 'But as we discussed, this is likely to be a lifelong commitment if it is going to be worthwhile to the NHS. 'There's no point in most people taking it for a couple of years and then have the weight bouncing back. 'You can argue possibly you're about to prepare for surgery or something, but in most cases it doesn't make any sense. 'Then I think there's a big issue around access. Most obesity occurs in poorer populations as wealthier populations tend to not be so affected. 'There's a massive sort of socio-economic inequality and there is a worry about this driving that inequality even further. 'Unless the NHS makes sure that these are available across the board equally, I think that's a major risk.' Prof Easton said recent studies had shown people who stopped taking the drugs had put the weight they lost back on within around a year. 'That's often true of any diet, people would say, and that's certainly my experience of having wrestled with my weight in diets over the years,' he said. 'All I would say that I found interesting from that review was that they were suggesting perhaps that weight returns even quicker after having been on GLP-1 drugs. 'Then speculating, because there was no way of knowing from that review, that perhaps it's because people are not changing the behaviours we've been talking about like exercise and other lifestyle changes, just relying on the drugs. 'When you stop them, of course, you're going to put weight back on. The switch is turned back off, or whatever it was. 'I mean very similar to, for example, statins or anti-hypertensive blood pressure medications, if you want lifelong effects, you have to keep on them lifelong.' 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'We're now in the third and fourth generation of these drugs, but the first generation of these drugs we've been using for 15 years for diabetes,' he said. 'There is nothing of concern that has emerged. In fact, all we're seeing are benefits. I'm not too worried about longer term side effects coming out. 'There is no real biological reason why there should be dangerous side-effects in the way that we know these drugs work. 'The benefits of the weight loss improvement in the diabetes are actually by themselves helping health and preventing other diseases, like cancer, heart attacks, renal failure, and potentially even reducing the risk of Alzheimer's disease. 'All those benefits, even if there was something that we hadn't really thought of that emerged down the line, I suspect that the harm of that is outweighed by the potential benefits of weight loss improvement in diabetes control.' Dr Cork said no drug is without side-effects and previous weight loss medications had failed because of them. 'There are side-effects, there are some concerning side-effects that tend to be very rare, but then you can monitor for those side-effects,' he said. 'As long as you're getting the correct care, as long as your GP is aware that you're taking them, then those should be identified. 'If you do find those side-effects, you can stop taking the drug.'