A New Hope for Oral Diabetes Medication

A novel oral medication, Orforglipron, is poised to potentially revolutionize type 2 diabetes treatment. The complete results of the first phase 3 study, “Achieve-1,” are scheduled for presentation at the American Diabetes Association’s (ADA) 85th Scientific Sessions in June, followed by publication in a peer-reviewed specialist journal. This announcement has generated considerable excitement within the medical community, particularly due to Orforglipron’s unique mechanism and promising clinical trial outcomes.

Orforglipron vs. Semaglutide: A Comparative Edge

Orforglipron is classified as a non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, administered orally once daily. One of its key advantages lies in its ease of use compared to the already approved oral GLP-1 agonist Semaglutide (Rybelsus, Novo Nordisk). Semaglutide requires strict adherence to a fasting state,taken 30 minutes before the first meal of the day. orforglipron, conversely, boasts a more flexible administration schedule, as it can be used regardless of meals and water intake. This flexibility could significantly improve patient compliance and overall treatment effectiveness.

achieve-1 Study: Important Improvements in HbA1c and Weight

The “Achieve-1” study involved 559 patients with type 2 diabetes,observed over a 40-week period. Participants were administered either 3 mg, 12 mg, or 36 mg of Orforglipron, or a placebo. The study revealed significant reductions in HbA1c levels, a key indicator of long-term blood sugar control.

• The average baseline HbA1c was 8.0%.
• HbA1c reduction ranged from 1.3 percentage points (3 mg) to 1.6 points (12 mg).
• Placebo group saw a reduction of only 0.1 percentage points.
• Reductions were statistically significant across all orforglipron dosages.
• More than 65% of patients on the highest dose achieved an HbA1c value of 6.5% or below, the target recommended by the American Diabetes Association.

The study also demonstrated notable benefits in terms of body weight reduction:

• Weight reduction ranged from 4.7% to 7.9%, depending on the dose.
• The placebo group experienced a weight reduction of only 1.6%.
• In absolute terms, this translated to a weight loss of 4.4 to 7.3 kg for Orforglipron, compared to 1.3 kg for placebo.

Lilly, the pharmaceutical company developing Orforglipron, believes there is potential for even greater weight loss, stating, It truly seems that the full weight loss has not yet been reached.

Side Effects: A Manageable Profile

The most common side effects reported in the “achieve-1” study were consistent with the known profile of GLP-1 receptor agonists, primarily gastrointestinal issues. These included:

• Diarrhea (up to 26%)
• Nausea (up to 18%)
• Vomiting (up to 14%)

These rates were significantly lower in the placebo group. The discontinuation rate due to adverse events was up to 8%. researchers noted that the side effect profile was a gastrointestinal similar to Semaglutid, but with diarrhea in the first place.Vomiting was less frequently enough reported than in Semaglutid. Importantly, no indications of liver toxicity were observed.

Expert Opinion: High Potential, Cautious Optimism

Professor Naved Sattar, a cardiometabolic expert at the University of Glasgow, expressed optimism regarding the findings. Speaking to the UK Science Media Center, he stated:

These are significant results. New oral active ingredients that reduce both blood sugar and weight significantly more than most existing diabetes medication are crucial for the future care for type 2 diabetes.
Professor Naved Sattar, University of Glasgow

Though, Sattar also emphasized the need for further research, noting:

There is a reservation that we do not yet know how this new therapy affects cardiovascular events – this will show future studies. It is also gratifying to hear from a cheap security profile, especially regarding the liver. It becomes exciting to see the full data.
Professor Naved Sattar, University of Glasgow

Looking Ahead: Approval and Availability

The “Achieve-1” phase 3 study is part of a larger development program encompassing seven studies. Additional results, particularly those related to weight loss from the “Attain” program, are anticipated in 2025. lilly plans to submit applications for approval for weight management to global regulatory authorities in 2025, with the submission for type 2 diabetes approval slated for 2026.

The company has expressed confidence in its ability to manage the global rollout without encountering supply chain disruptions. Information regarding the pricing of Orforglipron has not yet been disclosed.