An oral GLP-1 medication developed by pharmaceutical giant Eli Lilly has been found to be more effective for blood sugar control and weight loss as compared to the oral version of the popular drug semaglutide, according to results of the first head-to-head comparison of both the oral medications.
When the drug, called Orforglipron, becomes available in the market, doctors say it can be an “attractive option” for patients in whom metformin fails to control blood glucose levels. This is significant considering the oral medicines are easier to use as compared to all other GLP-1 medicines in the market which are injectables.
What did the study find?
When it comes to blood sugar control, the study found that orforglipron 12 mg reduced HbA1c (average blood sugar count of three months) by 1.71%, orforglipron 36 mg by 1.91% as compared to 1.23% with oral semaglutide 7 mg and 1.47% with oral semaglutide 14 mg. At the beginning of the study, the average HbA1c levels of the participants stood at 8.3%. An HbA1c level below 5.7% is considered to be normal, between 5.7% and 6.4% is considered to be pre-diabetes, and 6.5% or higher is considered to be diabetes.
When it comes to weight loss, the study found that participants on orforglipron 12mg lost 6.1% of their body weight and those on orforglipron 36 mg lost 8.2% after a year. To compare, those on semaglutide 7mg lost 3.9% and those on semaglutide 14mg lost 5.3%.
The results are based on data of 1,698 participants across the US, Argentina, China, Japan, Mexico and Puerto Rico.
Is there any reason to choose this drug over others?
“The study was mainly done to assess the drug impact on blood glucose levels and it shows that there might be some weight loss. I am not too impressed with the weight loss as it is not very significant. And the study has not compared the drug with the injectable versions that have been shown to lead to more weight loss,” said Dr Anoop Misra, chairman, Fortis C Doc Centre for Diabetes.
Dr Ambrish Mithal, chairman, diabetes and Endocrinology, Max Healthcare, raises similar concerns: “The 7 mg and 14 mg semaglutide are meant for blood sugar control — the study does not compare orforglipron to the higher 25 mg dose oral semaglutide, which has now been approved for weight loss.”
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Dr Misra says this might be an option for patients who have uncontrolled blood sugar levels despite taking medicines such as metformin. The high blood sugar control makes it a preferable choice as compared to oral semaglutide.
“One important thing to consider is that this drug seems to have more gastro-intestinal side effects than semaglutide. The GI side effects are one of the most potent deterrents to continued treatment. So, if it is higher for orforglipron, it can be a challenge,” explains Dr Mithal.
What about prices?
Both medicines are likely to be similarly priced as both are under patent. The injectable version of semaglutide, however, will go off patent next month, opening the market for cheaper, generic versions.
How does it compare to other weight-loss medicines in the same class?
A previous study — designed primarily to examine the weight loss properties of orforglipron — found that it was comparable to both the oral and injectable versions of its competition semaglutide but inferior to Eli Lilly’s own injectable weight loss drug tirzepatide. Those on the highest 36 mg dose of the medicine on average lost 12.4% of their body weight at 72 weeks, comparable to oral and injectable semaglutide, but lower than the 26% weight loss achieved with tirzepatide at 84 weeks.
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Why is the molecule important?
One of the biggest challenges of taking the new GLP-1 receptor agonist drugs — such as semaglutide and tirzepatide — is the hassle of getting the once-weekly shot. With the ease-of-use, an oral regimen is likely to make the drugs more accessible.
Another important distinction, which may make orforglipron the preferred pill, is that it is the first small molecule GLP-1 drug. To compare, the oral semaglutide is a peptide molecule or a chain of amino acids that are inserted in a delivery system that prevents it from degradation in the stomach. Small molecule drugs are generally easier and cheaper to manufacture than peptides that have a more complex structure, need a delivery mechanism, and are more sensitive to temperature, pH and other environmental factors. This also means there are no food or water restrictions for taking orforglipron.
