Daily pill tops oral semaglutide in diabetes and weight-loss trial
Orforglipron lowered blood sugar and weight more than oral semaglutide, but more patients reported gastrointestinal side effects.
By Priya Raghavan · Science Reporter
3 min read
A once-daily experimental pill from Eli Lilly produced greater blood sugar reductions and weight loss than oral semaglutide in a large trial of adults with type 2 diabetes, according to reporting by The Conversation. The results point to a possible new competitor in the fast-growing market for GLP-1 weight-loss and diabetes drugs, though side effects may limit use for some patients.
The 52-week phase 3 trial enrolled 1,698 adults with type 2 diabetes in six countries, The Conversation reported. Researchers compared orforglipron, a daily tablet, with currently available oral semaglutide products.
The main measure was HbA1c, a blood test that reflects average blood sugar over roughly three months and is commonly used to assess diabetes control. Participants began the study with an average HbA1c of 8.3%, according to The Conversation.
Trial results
After 52 weeks, orforglipron reduced HbA1c by an average of 1.71% to 1.91%, while oral semaglutide lowered it by 1.47%, The Conversation reported. The findings meant orforglipron met the study goal of showing it was at least as effective as oral semaglutide and also performed better on blood sugar reduction.
Weight loss was also greater among patients taking orforglipron. Participants on the drug lost an average of 6.1kg to 8.2kg, compared with 5.3kg among those taking oral semaglutide, according to The Conversation.
Both drugs are part of the broader GLP-1 field, which targets pathways linked to appetite, digestion and insulin release. Semaglutide, sold under brand names including Ozempic and Wegovy, is widely used in injectable form for diabetes and weight management, The Conversation reported.
GLP-1 drugs imitate the effects of a gut hormone released after eating. According to The Conversation, that hormone helps signal fullness to the brain, slows digestion and promotes insulin release, making the drug class useful for type 2 diabetes management and weight loss.
Convenience and side effects
Injectable GLP-1 medicines require shots into areas such as the abdomen, thigh or back of the arm, which can deter people who dislike needles or do not want to self-inject, The Conversation reported. They also require refrigeration through the supply chain, creating barriers in places where cold storage is unreliable.
Oral semaglutide avoids injections but has its own limits. The Conversation reported that it must be taken on an empty stomach, with users waiting 30 minutes before eating or drinking, and that only about 1% of the ingested drug is absorbed.
Orforglipron differs from semaglutide because it is a small-molecule drug, The Conversation reported. That means it is a synthetic chemical compound that can be absorbed through the gut wall and act on GLP-1 receptors, rather than a peptide drug whose structure resembles the natural hormone.
That distinction could matter for production and access. Small-molecule drugs are cheaper and simpler to manufacture than peptide-based medicines such as semaglutide, and orforglipron does not require refrigeration, according to The Conversation.
The trial also showed a tolerability concern. About 59% of participants taking orforglipron reported gastrointestinal symptoms such as nausea, vomiting, diarrhea or constipation, compared with 37% to 45% of those on semaglutide, The Conversation reported.
Discontinuation rates were higher with orforglipron. Around 10% of patients taking it stopped treatment because of adverse effects, compared with 4% to 5% of participants taking semaglutide, according to The Conversation.
No head-to-head trial has compared injectable GLP-1 medicines with orforglipron, The Conversation reported. Trials of orforglipron in people with obesity who do not have diabetes are still under way.
This story draws on original reporting from ScienceDaily.