- Oral GLP 1 agonist orforglipron led to about ten percent weight loss in people with obesity and type 2 diabetes
- The pill avoids injections and is expected to cost less than current injectable drugs
- Side effects resemble those of injectable GLP 1 medicines and remain dose dependent
Drugs that mimic the hormone GLP 1 have transformed obesity and diabetes care in recent years.
Brands such as Ozempic and Mounjaro have shown substantial weight loss and cardiometabolic benefits but are given as regular injections, need cold storage and can be very expensive.
Drug companies are now racing to produce effective GLP 1 pills that are simpler to use and more affordable. Orforglipron, developed by Eli Lilly, is one of the leading candidates.
A phase 3 trial published in The Lancet tested orforglipron in more than 1,500 adults from ten countries. All participants had obesity and type 2 diabetes.
They received:
- Daily orforglipron at varying doses, or
- A matched placebo
All participants also received advice on healthy eating and physical activity.
After 72 weeks:
- People on the highest dose, 36 milligrams daily, lost about ten percent of their body weight
- Those on placebo lost about two percent
- Earlier work in people with obesity but without diabetes found around twelve percent weight loss on the pill
These results are below the approximately twenty two percent weight loss seen with weekly injectable Mounjaro over similar time periods, but still represent clinically meaningful change.
Side effects and tolerability
The safety profile of orforglipron was broadly in line with other GLP 1 drugs. Common side effects, especially at higher doses, included:
- Nausea and vomiting
- Constipation
- Diarrhoea
These effects tend to appear early in treatment and can often be managed by slower dose escalation and dietary adjustments, but they remain a limiting factor for some people.
Cost, access and future role
According to the lead author, Deborah Horn of UTHealth Houston, if orforglipron is approved by the United States Food and Drug Administration it is expected to become available in 2026 at a substantially lower cost than current injectable GLP 1 drugs.
Injectable GLP 1 medicines can cost more than 1,000 US dollars a month in the United States.
Independent analyses suggest that generic versions could be manufactured for a few dollars a month, raising questions about equity of access, especially in lower income countries where the health burden of obesity is rising.
GLP 1 medicines were developed for diabetes treatment but are now being studied across a wide range of conditions, from cardiovascular disease and sleep apnoea to addiction.
An effective oral option would be easier to deploy at scale in both diabetes and obesity care.
