Oral GLP-1 drugs: a committee opinion, registry numbers and an early Phase II signal

This week's question

Oral GLP-1 receptor agonists are moving from trials towards clinics. Three reports this week sit at different stages of that path. One is a regulatory recommendation, one is a set of phase 3 registry results, and one is an early Phase II trial. The question is what these reports add up to, and what they still leave open.

What the studies showed

Regulatory step. The EMA committee report covers the CHMP meeting of 12-15 October 2026. The committee recommended a marketing authorisation for Foundayo (orforglipron), from Eli Lilly Nederland B.V. It is a once-daily tablet for weight management and for treatment of type 2 diabetes in adults. The committee described it as an alternative to injectable and other oral GLP-1 receptor agonists. This is a recommendation only. The European Commission decision is pending. The highlights give no trial results, doses or safety data.

Phase 3 registry results. The ACHIEVE-2 registry report describes a randomised, open-label phase 3 trial. It compared once-daily orforglipron with dapagliflozin in adults with type 2 diabetes and inadequate control on metformin. The registry lists 962 participants and Eli Lilly as sponsor. The primary outcome was change in HbA1c from baseline to week 40, labelled a noninferiority analysis. Least squares mean changes, all falls, were:

• Orforglipron 3 mg: -1.32
• Orforglipron 12 mg: -1.74
• Orforglipron 36 mg: -1.73
• Dapagliflozin 10 mg: -0.76

The falls were numerically larger in all three orforglipron groups. The record gives no confidence intervals, no noninferiority margin and no p values. It does not say whether noninferiority or superiority was formally shown. It also reports no safety results.

Early Phase II signal. The HRS-7535 trial report describes a randomised, double-blind, placebo-controlled trial in Chinese adults. HRS-7535 is an oral small-molecule GLP-1 receptor agonist. All 155 participants were already on metformin plus an SGLT2 inhibitor. At week 16, HbA1c fell by 16 mmol/mol with 30 mg and by 20 mmol/mol with 60 mg. It fell by 4 mmol/mol with placebo. Both doses beat placebo (p<0.0001). HbA1c below 53 mmol/mol (7.0%) was reached by 51.0% with 30 mg, 66.0% with 60 mg and 9.8% with placebo. Body weight loss was reported as -2.4% with 60 mg and -0.7% with placebo. The abstract gives no 30 mg weight result. Most adverse events were mild to moderate, and gastrointestinal events were the most common. No severe hypoglycaemia was reported. Event rates by group were not given.

Where they agree and where they do not

The two efficacy reports point the same way. In each, the oral GLP-1 receptor agonist lowered HbA1c, and the comparison group showed a smaller fall. The regulatory report shows that at least one oral agent has reached the stage of a positive committee opinion.

That is where the agreement ends. These studies cannot be lined up against each other, for several reasons:

• Different drugs. ACHIEVE-2 tested orforglipron. The Phase II trial tested HRS-7535.
• Different comparators. ACHIEVE-2 used dapagliflozin 10 mg. The HRS-7535 trial used placebo.
• Different background therapy. ACHIEVE-2 enrolled people on metformin. The HRS-7535 trial enrolled people on metformin plus an SGLT2 inhibitor.
• Different durations and units. ACHIEVE-2 measured at week 40 and reported percentage units. The HRS-7535 trial measured at week 16 and reported mmol/mol, with percentages alongside.
• Different populations. The HRS-7535 trial enrolled only Chinese participants. The ACHIEVE-2 record gives no participant characteristics.

The quality of the evidence also differs. The HRS-7535 result comes from a journal abstract (Diabetologia) and a double-blind design. The ACHIEVE-2 result is a sponsor-run registry entry from an open-label trial. The regulatory item contains no data at all. The HRS-7535 trial was funded by Jiangsu Hengrui Pharmaceuticals, and ACHIEVE-2 was sponsored by Eli Lilly, the applicant for Foundayo.

The reports also do not say that the ACHIEVE-2 results were part of the evidence behind the CHMP opinion. That link should not be assumed.

What is still unknown

• Formal ACHIEVE-2 results. The noninferiority margin, confidence intervals and whether noninferiority or superiority was shown are all missing from the posted text.
• Safety and tolerability. None of the three reports gives gastrointestinal event rates by group. The ACHIEVE-2 record gives no safety data, and the EMA highlights give none either. Without these data, tolerability and the balance of benefit and harm cannot be judged from these reports.
• Weight. ACHIEVE-2 weight change is not in the posted text. The HRS-7535 30 mg weight result is also missing.
• Hard outcomes and durability. Both trials used HbA1c as the main outcome, a surrogate. Neither report gives cardiovascular or kidney outcomes. The Phase II trial lasted only 16 weeks and had 155 participants.
• Head-to-head comparisons. No report compares an oral GLP-1 receptor agonist with an injectable one, or one oral agent with another.
• What the EMA saw. The highlights do not describe the trial evidence behind the Foundayo opinion.
• Final decisions. The European Commission decision on Foundayo is pending.

For your clinic on Monday

Nothing here changes prescribing. A CHMP opinion is a recommendation, not an approval. Please do not tell patients that an oral orforglipron option is available to them.

If patients ask about a new once-daily tablet, you can say that a European committee has recommended one and that final decisions are awaited. The registry numbers are a general signal only. They are not a basis for choosing between drugs for an individual patient.

Before any new oral incretin enters your practice, look for these in the full publications and regulatory reviews:

• The formal noninferiority and superiority results.
• Gastrointestinal tolerability and discontinuation rates.
• Weight results at each dose.
• Who was enrolled, and whether they resemble your patients.
• Cost and the other effects of each option, which these reports do not cover.

For now, current guidelines and the drugs actually available in India remain the practical guide.

India box: An expert committee of India's national drug regulator has recommended import and marketing permission for orforglipron. As of September 2026 there is no final approval and no launch in India. (Indian regulatory status as checked in September 2026.)