While GLP-1 weight-loss drugs such as Wegovy and Mounjaro have helped patients lose weight, a major concern has been weight regain once the therapy is stopped.
Now, a new study by US scientists suggests that a daily pill may help prevent that rebound weight gain.
According to a clinical trial led by Weill Cornell Medicine and NewYork-Presbyterian, switching to the once-daily orforglipron pill may not only help maintain weight loss but also preserve cardiometabolic benefits.
Orforglipron is US drugmaker Eli Lilly's first oral pill for weight loss, marketed as Foundayo. In April, it received approval from the US Food and Drug Administration (FDA).
Weight Loss With Daily Pill Orforglipron
In the Eli Lilly-funded trial, published in the journal Nature Medicine, researchers found that patients in the Phase 3b clinical trial maintained around 75-80 per cent of their weight loss. They also experienced several additional health benefits, including:
- Reduced waist circumference
- Improved blood pressure
- Better blood sugar control
- Lower triglyceride levels
- Improved cholesterol levels
"Obesity is a chronic condition like high blood pressure, elevated cholesterol, or high blood sugar and requires chronic treatment," said Louis J. Aronne, who also serves as a consultant for Eli Lilly.
The Clinical Trial
The ATTAIN-MAINTAIN trial enrolled patients who had already achieved substantial weight loss that later plateaued while taking weekly injectable GLP-1 drugs during the SURMOUNT-5 trial.
The study randomized:
- 205 patients taking tirzepatide
- 171 patients taking semaglutide
Participants were assigned to either daily orforglipron or placebo treatment for one year.
The results showed that patients switching from tirzepatide to orforglipron maintained an average of 74.7 per cent of their body weight reduction, compared with 49.2 per cent in the placebo group.
Meanwhile, patients who switched from semaglutide to orforglipron maintained 79.3 per cent of their body weight reduction, compared with 37.6 per cent in the placebo arm.
Over the 52-week trial period, participants treated with orforglipron gained:
- An average of 5 kg (11 lbs) in the tirzepatide group
- An average of 1 kg (2.2 lbs) in the semaglutide group
How The Daily Pill Orforglipron Works
Eli Lilly licensed orforglipron, the active ingredient in Foundayo, from a Japanese pharmaceutical company in 2018.
Like injectable GLP-1 drugs, Orforglipron is available in six doses ranging from 0.8 mg to 17.2 mg. Patients typically begin at the lowest dose and gradually increase under medical supervision.
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Unlike some oral GLP-1 drugs, people taking orforglipron do not need to restrict food or drink intake after taking the pill. Researchers say the small molecule is absorbed quickly into the bloodstream and reaches target tissues efficiently.
Orforglipron: Side Effects And Safety Concerns
Foundayo is not approved for use in children and carries warnings about potential thyroid tumours, including thyroid cancer.
The drugmaker advises patients to watch for symptoms such as:
- Lump or swelling in the neck
- Hoarseness
- Trouble swallowing
- Shortness of breath
Other common side effects include:
- Nausea
- Constipation
- Diarrhoea
- Vomiting
- Indigestion
- Stomach pain
- Headache
- Swollen belly
- Fatigue
- Belching
- Heartburn
- Gas
- Hair loss.
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