Indianapolis, June 21, 2025 /PRNewswire/ — Eli Lilly (LLY) is making waves in the diabetes treatment landscape. The pharma giant today unveiled positive Phase 3 results for orforglipron, an investigational once-daily oral drug, positioning it as a potential game-changer in the fight against type 2 diabetes.
The ACHIEVE-1 trial delivered compelling data, published simultaneously in *The New England Journal of Medicine*. The study showcased orforglipron’s efficacy in lowering A1C levels – a key marker of blood sugar control – in adults with type 2 diabetes who were managing their condition with diet and exercise alone. Across the different doses tested (3mg, 12mg, and 36mg), the drug achieved an average A1C reduction ranging from 1.3% to 1.6%. Impressively, these improvements were observed as early as four weeks into the trial.
“This is a significant development,” noted a healthcare analyst following the announcement, “because it’s a pill, and the market is hungry for more convenient options.”
Beyond glycemic control improvements, orforglipron also demonstrated a positive impact on weight management. At the highest dose (36mg), patients experienced an average weight loss of 16 pounds (7.9%) by week 40, a noteworthy outcome from a secondary endpoint perspective.
The investigational once-daily pill lowered A1C by an average of 1.3% to 1.6% across doses, with improvements seen as early as four weeks, in adults with type 2 diabetes
In ACHIEVE-1, orforglipron also led to an average weight loss of 16.0 lbs (7.9%) at the highest dose by week 40 in a key secondary endpoint
The safety profile of orforglipron was consistent with the established GLP-1 class
The safety profile of orforglipron appears to be consistent with the well-established GLP-1 receptor agonist class of diabetes medications. The most frequently reported side effects were gastrointestinal-related, mirroring the common experiences with other drugs in this category.
Dr. Julio Rosenstock, lead investigator of the trial, highlighted the significance of these findings. “The ACHIEVE-1 trial demonstrated that orforglipron, a novel oral small-molecule GLP-1, achieved clinically meaningful reductions in A1C and body weight over 40 weeks in adults with type 2 diabetes,” he stated. “The early onset of glycemic improvement, observed as soon as four weeks, reinforces the therapeutic potential of orforglipron as an effective, oral GLP-1 therapy for early type 2 diabetes treatment. These findings support further investigation in broader populations and longer-duration studies.”
Here’s a snapshot of the key findings:
|
Full Results |
|||||
|
Orforglipron 3 mg |
Orforglipron 12 mg |
Orforglipron 36 mg |
Placebo
|
||
|
Primary Endpoint |
|||||
|
A1C reduction from baseline of 8.0 %i |
Efficacy estimand |
1.3 % |
1.6 % |
1.5 % |
0.1 % |
|
Treatment-regimen estimand4 |
1.2 % |
1.5 % |
1.5 % |
0.4 % |
|
|
Key Secondary Endpointsii |
|||||
|
Percent weight reduction from baseline of 90.2 kg (198.9 lbs)i,iii |
Efficacy estimand |
4.7 % |
6.1 % |
7.9 % |
1.6 % |
|
Treatment-regimen estimand |
4.5 % |
5.8 % |
7.6 % |
1.7 % |
|
|
Weight reduction from baseline of 90.2 kg (198.9 lbs)i,iii |
Efficacy estimand |
4.4 kg |
5.5 kg |
7.3 kg |
1.3 kg (2.9 lbs) |
|
Treatment-regimen |
4.2 kg (9.3 lbs) |
5.2 kg (11.5 lbs) |
7.2 kg (15.8 lbs) |
1.5 kg (3.4 lbs) |
|
|
Percent of participants achieving A1C i |
Efficacy estimand |
72.9 % |
76.2 % |
74.9 % |
28.0 % |
|
Treatment-regimen estimand |
68.1 % |
72.9 % |
72.7 % |
33.0 % |
|
|
Percent of participants achieving A1C ≤6.5 %i,ii |
Efficacy estimand |
61.5 % |
62.3 % |
66.0 % |
13.5 % |
|
Treatment-regimen |
56.9 % |
58.1 % |
61.9 % |
14.9 % |
|
|
Percent of participants |
Efficacy estimand |
17.7 % |
25.8 % |
23.9 % |
3.8 % |
|
Treatment-regimen estimand |
16.8 % |
23.9 % |
21.5 % |
3.8 % |
|
|
Fasting serum glucose of 147.5 mg/dLi |
Efficacy estimand |
30.6 mg/dL |
37.4 mg/dL |
37.8 mg/dL |
1.1 mg/dL |
|
Treatment-regimen estimand |
30.7 mg/dL |
36.5 mg/dL |
34.7 mg/dL |
10.8 mg/dL |
|
The ACHIEVE-1 trial results solidify orforglipron’s promise. The study showed that the drug met its primary endpoint of superior A1C reduction compared to placebo, with reductions ranging from 1.3% to 1.6%. Key secondary endpoints showed that up to 76.2% of participants taking orforglipron achieved the ADA treatment target A1C of 7%, with 66% achieving an A1C of ≤6.5% and 25.8% reaching 5.7%, which is defined as a normal A1C value. Improvements in A1C were also observed as early as four weeks, coupled with similar reductions in fasting serum glucose.
Lilly is clearly excited by the results, with Dr. Jeff Emmick, senior vice president of product development, stating, “This convenient once-daily pill with no restrictions on food and water intake could be an option for millions of people with type 2 diabetes who prefer oral medications over injectables.”
Lilly is wasting no time in advancing its development program. Later this year, investors can anticipate topline results from ACHIEVE-2, comparing orforglipron to dapagliflozin, and ACHIEVE-3, pitting orforglipron against oral semaglutide. Data from the ATTAIN program, which is studying the drug’s potential in obesity, are also slated for release in the third quarter. The company is targeting regulatory submissions for weight management by the end of the year and for type 2 diabetes treatment in 2026.
The road ahead is promising. With these new data in hand, and with other late-stage readouts expected soon, orforglipron could reshape the treatment landscape for type 2 diabetes and potentially offer new avenues for weight management. While the market has seen progress in oral GLP-1 agonists, the convenience, safety, and efficacy shown by orforglipron could make it a strong contender in the booming market for diabetes and weight-loss treatments.
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