Lilly’s oral GLP-1 pill cuts blood sugar and weight without injections—Here’s what the breakthrough data shows

How Did Lilly’s Oral GLP-1 Pill Perform In Phase 3?

Eli Lilly and Company has reported successful topline results from the Phase 3 ACHIEVE-1 trial evaluating orforglipron, a once-daily oral small molecule GLP-1 receptor agonist. According to the company, the investigational therapy demonstrated statistically significant reductions in A1C levels and body weight, with a safety profile comparable to injectable GLP-1 therapies. These results mark the first time a non-peptide oral GLP-1 agonist has successfully completed a Phase 3 study, and could reshape treatment accessibility for type 2 diabetes and obesity globally.

The company emphasised that orforglipron, which does not require administration with food or water, may be produced and distributed at global scale without supply chain constraints. With an estimated 760 million adults projected to have diabetes by 2050, Lilly views orforglipron as a scalable, daily-use solution with high potential public health impact.

What Are The Key Efficacy Results From The ACHIEVE-1 Trial?

In ACHIEVE-1, orforglipron achieved the primary endpoint of A1C reduction at 40 weeks, with reductions ranging between 1.3% and 1.6% from a baseline of 8.0%. At the highest dose, over 65% of participants achieved an A1C of 6.5% or lower, which falls below the American Diabetes Association‘s threshold for diagnosing diabetes.

Weight loss, a key secondary endpoint, also favoured orforglipron. Participants receiving the 36 mg dose experienced an average weight loss of 7.3 kg (16.0 lbs), equivalent to 7.9% of body weight. Notably, weight loss had not plateaued at the study’s 40-week endpoint, suggesting continued benefit may be possible with extended treatment duration.

The efficacy estimand data indicated consistent performance across all dosage arms:

• 3 mg dose: 1.3% A1C reduction, 4.4 kg weight loss (9.7 lbs)

• 12 mg dose: 1.6% A1C reduction, 5.5 kg weight loss (12.2 lbs)

• 36 mg dose: 1.5% A1C reduction, 7.3 kg weight loss (16.0 lbs)

• Placebo: 0.1% A1C reduction, 1.3 kg weight loss (2.9 lbs)

Under the treatment-regimen estimand, the drug’s glycaemic and weight loss efficacy remained statistically significant at all doses.

How Does Orforglipron Compare On Safety?

The safety and tolerability profile of orforglipron closely mirrored that of injectable GLP-1 therapies. The most frequent adverse events were gastrointestinal, including diarrhea, nausea, dyspepsia, constipation, and vomiting. Most events were reported as mild to moderate.

Discontinuation due to adverse events remained relatively low—6% (3 mg), 4% (12 mg), and 8% (36 mg) compared to 1% for placebo. No liver toxicity signals were identified in the trial, reinforcing the safety data seen in prior studies.

What’s Next For Orforglipron And The Broader Development Program?

The ACHIEVE-1 trial is the first among seven global Phase 3 trials in Lilly’s ACHIEVE and ATTAIN programs evaluating orforglipron for type 2 diabetes and obesity-related conditions. The company noted that over 6,000 participants have been enrolled across five global trials since the program began in 2023.

Lilly expects to present the full data at the 85th Scientific Sessions of the American Diabetes Association (ADA), with publication in a peer-reviewed journal to follow. The company also anticipates submitting orforglipron for regulatory approval for weight management before the end of 2025, followed by submission for type 2 diabetes in 2026.

What Is Orforglipron And Why Is It Significant?

Orforglipron is the first oral, non-peptide GLP-1 receptor agonist to advance this far in clinical development. The compound was discovered by Chugai Pharmaceutical and licensed by Lilly in 2018. Unlike injectable GLP-1 drugs such as semaglutide, orforglipron is a small molecule that can be taken without regard to food or water timing.

This convenience factor, combined with demonstrated glucose-lowering and weight-reducing effects, may expand patient access, especially in populations where injectable therapies are difficult to administer or accept.

In addition to diabetes and weight management, orforglipron is being studied for related conditions such as obstructive sleep apnea and hypertension in patients with obesity, pointing to broader applications in metabolic health.

How Has Eli Lilly’s Stock Responded To Orforglipron Trial Results?

Eli Lilly and Company (NYSE: LLY) has seen a significant uplift in its stock price following the announcement of positive Phase 3 data. On April 17, 2025, LLY shares surged 14.3%, closing at $839.96. This jump reflects the market’s confidence in the commercial potential of orforglipron and its impact on Lilly’s leadership position in the GLP-1 therapeutic segment.

Buy-side interest in Lilly has been reinforced by bullish analyst commentary, with several brokerages maintaining ‘Buy’ ratings and adjusting their price targets upward. The company’s consistent track record of innovation in the metabolic and cardiovascular space continues to attract long-term investor interest.

What Do Institutional Flows Reveal About Investor Confidence?

Eli Lilly’s institutional ownership stood at 82.53% as of the latest data. Over the past 12 months, there have been 2,788 institutional buyers contributing $74.16 billion in inflows, compared to 2,049 sellers recording outflows of $39.34 billion. This strong net positive flow underscores confidence from large funds in the sustainability of Lilly’s drug pipeline and revenue growth trajectory.

While global equity markets have seen FIIs as net sellers in broader indices in recent weeks, Lilly continues to witness support from domestic institutions and long-only global funds, particularly those focused on healthcare innovation.

Is Eli Lilly A Buy After Orforglipron’s Breakthrough?

With orforglipron demonstrating efficacy and safety comparable to injectable GLP-1s, and offering the added convenience of oral administration, its potential market reach is substantial. Analysts forecast that if approved, orforglipron could be used widely in primary care settings, especially in geographies where access to injections is limited or patient adherence is a challenge.

Given the strong trial results, positive sentiment, and accelerating institutional flows, Eli Lilly’s stock is widely viewed as a ‘Buy’. Investors bullish on the future of obesity and diabetes therapeutics may find LLY a compelling long-term hold, especially with multiple regulatory milestones ahead and continued momentum in its incretin portfolio.