Weight-loss injections, such as Wegovy and Mounjaro, have transformed how we treat obesity. Around 1.6 million adults in Great Britain have used weight-loss drugs in the past year, with the vast majority of patients buying these drugs privately.
The issue with these weight-loss drugs is that, despite their success in shedding weight while patients are taking them, studies report significant weight regain when people come off them. What's more, the health benefits seen when taking these drugs, such as reductions in blood pressure, blood glucose and lipids, also disappear.
In the UK, a private prescription for Mounjaro costs about £300 a month. And therein lies the issue. The ongoing cost is unsustainable for most patients.
The reason these drugs are so expensive is mainly due to the way they are made. First, the active components of these drugs are peptides - small proteins that are rapidly degraded in the stomach and digestive tract, meaning they must be administered via an injection. Second, the injector pens are expensive to make and they must be stored in a fridge.
Orforglipron (brand name: Foundayo), a once-daily pill-based weight-loss drug that targets the same GLP-1 system as Wegovy, has recently been approved by the US Food and Drug Administration for treating obesity. Rather than the active compound being a peptide, it is instead a "small molecule", meaning it can withstand the harsh environment of the digestive system and is much cheaper to make and store. (Most drugs, including aspirin, ibuprofen and statins, are small-molecule drugs.)
This makes orforglipron a promising new arrival on the weight-loss market, with the potential to democratise access to these important medications. In the US, the cost of a month's supply of orforglipron is between US$149 and US$299 (£112-£224), compared with over US$1,000 for a monthly supply of Mounjaro.
Clinical trials have shown that orforglipron results in just over 15% body weight loss in adults with obesity, placing it on par with that seen with Wegovy , but significantly lower than the 21% weight loss seen with Mounjaro.
What is much more interesting, however, is the prospect that patients could use orforglipron to tackle the big problem of weight loss drugs: the rapid weight regain seen following their cessation.
Keeping the weight off
Researchers recently published findings from a trial investigating whether weight loss achieved through either Wegovy or Mounjaro could be sustained by switching to orforglipron.
The study recruited patients who had successfully lost at least 5% of their body weight over 72 weeks while on one of the two existing weight-loss jabs. Patients were taken off their original medication and given either orforglipron or a placebo drug for 52 weeks.
Among patients who originally took Mounjaro, those on placebo regained just over 50% of the lost weight at week 52. In contrast, those who took orforglipron regained just 26%, with over two-fifths of participants maintaining over 80% of their body weight reduction.
Similar results were seen in patients who had originally taken Wegovy, with those taking a placebo pill regaining 62% of their lost body weight, compared to 21% weight regain in those taking orforglipron.
Across both groups, people who took orforglipron also saw lasting improvements in key health markers, including blood sugar, blood pressure, insulin and cholesterol levels.
The trial was small - just over 100 people in each group - but it suggests a promising path: that weight loss achieved through these medications can be maintained in the long term, along with their wider health benefits, in a way that may also be more affordable.
Orforglipron is not yet licensed in the UK for weight loss. Assuming it is approved by the UK's Medicines and Healthcare products Regulatory Agency, it is anticipated to be available late 2026 to early 2027.
Simon Cork does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
