Orforglipron: slimming pill and the status of its EU authorisation

Orforglipron is a non-peptide active substance. This means that, chemically speaking, it is not a peptide. It activates the GLP-1 receptor. Active substances used as weight-loss injections also act on this receptor.

The weight-loss pill is to be taken once daily. According to the dosing regimen examined, there are no restrictions regarding food or water intake. Orforglipron could therefore provide an oral treatment option for people who prefer a tablet to an injection.

Foundayo is the proposed trade name of the medicine. The applicant is Eli Lilly Nederland B.V. No conclusions regarding market launch, price or reimbursement can yet be drawn from the EMA’s positive opinion.

The effectiveness of orforglipron depends, amongst other things, on the group of people studied. In cases of overweight and obesity, initial weight, comorbidities and the dosing regimen must also be taken into account.

The figure of 11.2 per cent from ATTAIN-1 is an average. It does not predict how much weight an individual will lose. Nor can it be deduced from the result whether the effect will persist after treatment has ended.

The side effects most frequently cited by the EMA relate to the digestive system. These include:

• Nausea
• Vomiting
• Diarrhoea

In the ATTAIN-1 trial, depending on the dose, approximately 5.3 to 10.3 per cent of participants discontinued treatment due to adverse events. When assessing this weight-loss pill, therefore, tolerability is just as important as efficacy.

Anyone already taking medication for weight loss or diabetes should not stop taking it on their own or replace it with orforglipron. This also applies to switching from weight-loss injections to oral tablets. Such a change should be managed by a doctor.

The recommended indication is narrower than the term ‘weight-loss pill’ might suggest. Foundayo is intended for adults with inadequately controlled type 2 diabetes where metformin is not suitable. Orforglipron should then be used as the sole pharmacological treatment.

The EMA’s positive opinion does not mean that Foundayo has already been authorised in the EU. Nor is it a general authorisation for weight loss and weight reduction in all people with obesity.

Whether the active ingredient might be suitable for a particular person therefore does not depend solely on their BMI or on a preference for a tablet form. The recommended indication and the individual’s specific treatment situation are the decisive factors.

Although the ACHIEVE-3 trial compared orforglipron with semaglutide, both active substances were taken orally. The study ran for 52 weeks. It therefore does not show whether the weight-loss pill is superior to or equivalent to an injectable GLP-1 treatment.

The authors of ATTAIN-MAINTAIN cite the one-year duration of their study as a limitation. The long-term trend in weight loss also remains unclear.

Ongoing treatment should not be altered without consulting a doctor. This also applies to people who wish to switch from an injection to Orforglipron because it is taken orally.

In cases of severe obesity, surgery may be considered alongside drug treatment. It is an option for a BMI of 40 or above. For a BMI between 35 and 40, this applies if there is also a condition such as diabetes.

Bariatric surgery does not bring medical care to an end. Following the procedure, a long-term change in lifestyle and regular check-ups are required. Whether medication or surgery is considered must be assessed on a case-by-case basis by a doctor.