Oral GLP-1 agonists: early HbA1c data, regulators acting, safety data still missing

This week's question

Oral GLP-1 receptor agonists are moving from early trials toward regulators. Four reports this week show different stages of that path. One is a phase II trial of a small-molecule drug. One is registry data from a phase 3 trial. One is a European committee recommendation. One is a list of Indian trial permissions. The question for Sunday Rounds is simple: how far along is this class, and what can a doctor in India say about it today?

What the studies showed

Phase II data: HRS-7535. The HRS-7535 trial report describes a randomised, double-blind, placebo-controlled trial. It enrolled 155 Chinese adults with type 2 diabetes who were already on metformin and an SGLT2 inhibitor. HbA1c fell by 16 mmol/mol with 30 mg and by 20 mmol/mol with 60 mg, against 4 mmol/mol with placebo (p<0.0001 for both doses). HbA1c below 53 mmol/mol (7.0%) was reached by 51.0%, 66.0% and 9.8% of participants respectively. The trial lasted 16 weeks and was funded by Jiangsu Hengrui Pharmaceuticals. The abstract says most adverse events were mild to moderate and that gastrointestinal events were the most common. It gives no event rates by group.

Phase 3 registry data: orforglipron. The ACHIEVE-2 registry report covers an open-label trial of 962 adults on metformin. It compares orforglipron with dapagliflozin. Least squares mean HbA1c change at week 40, in percentage units, was -1.32, -1.74 and -1.73 with orforglipron 3 mg, 12 mg and 36 mg. It was -0.76 with dapagliflozin 10 mg. All four values are falls in HbA1c. The primary analysis is labelled noninferiority. The posted text gives no margin, confidence intervals, p values or safety data. It also gives a "spread" figure for each group without saying what it is. So the record does not show whether noninferiority or superiority was formally met.

Europe: a positive opinion. According to the EMA meeting report, the CHMP recommended a marketing authorisation for Foundayo (orforglipron) for weight management and type 2 diabetes in adults. The European Commission decision is pending. The highlights contain no trial results.

India: trial permissions. The CDSCO committee report covers the Subject Expert Committee meeting of 07.10.2026. The committee recommended permission for four clinical trials. One is a Dr. Reddy's Phase I/III trial of semaglutide tablets 1.5 mg, 4 mg and 9 mg. It is double-blind and compares the firm's tablets with RYBELSUS® in adults with inadequately controlled type 2 diabetes. Another is an Eli Lilly phase III trial of LY3502970. The committee text gives only that code. It does not name the drug class or the condition studied, so its relevance to this theme cannot be judged from the report. The other two entries are insulin products and are outside this theme.

Where they agree and where they do not

On glucose, HRS-7535 (against placebo) and orforglipron (against dapagliflozin) both lowered HbA1c in the data reported. The CHMP recommended Foundayo, and the CDSCO committee recommended permission for an oral semaglutide trial. Neither regulatory report includes efficacy data.

Beyond that, the studies cannot be compared with each other. The differences are large:

• HRS-7535 was tested against placebo, on top of metformin and an SGLT2 inhibitor, for 16 weeks, in Chinese participants.
• Orforglipron was tested against dapagliflozin, on metformin, with the primary outcome at week 40, in an open-label design.
• The HRS-7535 results are given in mmol/mol with percentage equivalents. The ACHIEVE-2 record gives least squares mean change in percentage units only, with an undefined "spread" and no confidence intervals.

Different drugs, comparators, background therapy, durations and populations mean the HbA1c figures should not be placed side by side to rank the drugs. The HRS-7535 trial also had no active comparator. It says nothing about how that drug compares with other GLP-1 drugs.

The regulatory reports also sit at different levels. A CHMP opinion is a recommendation about marketing. A CDSCO committee recommendation is about permission to run a trial. The Indian committee advises the DCGI, and the final decision rests with the DCGI. These steps are not the same, and neither is a final approval for prescribing.

The India status of orforglipron needs care. The ACHIEVE-2 and EMA reports both carry a note that an expert committee of India's regulator has recommended import and marketing permission for orforglipron. As of September 2026 there was no final approval and no launch in India.

What is still unknown

• Safety and tolerability. The HRS-7535 abstract gives no gastrointestinal event rates by group. The ACHIEVE-2 record gives no safety results, no side effects and no discontinuation data. The EMA highlights give none for Foundayo.
• Formal comparison with dapagliflozin. The noninferiority or superiority result for ACHIEVE-2 is not in the posted text. Read the full publication or regulatory review.
• Weight. For HRS-7535, weight loss was reported as -2.4% with 60 mg and -0.7% with placebo. The abstract gives no 30 mg result and no significance test. The ACHIEVE-2 text reports no weight data.
• Hard outcomes. None of the reports includes cardiovascular or kidney outcomes. HbA1c and weight are surrogate outcomes.
• Durability. The HRS-7535 trial lasted 16 weeks. This is too short to show long-term safety or lasting effect.
• Indian data. The Dr. Reddy's trial has only been recommended for permission, and the CDSCO text gives no results. The same text does not say what drug class or condition the LY3502970 trial concerns.
• Orforglipron in India. As of September 2026 there was no final approval and no launch.

For your clinic on Monday

Nothing in these four reports changes current prescribing. The CDSCO entries concern clinical trials, not products for prescribing. The EMA opinion is not yet a European Commission decision. The orforglipron HbA1c data come from a sponsor registry record, and the HRS-7535 data come from a small phase II trial.

If a patient asks about orforglipron, you can say that a European committee has recommended it, that final decisions are awaited, and that in India an expert committee has recommended import and marketing permission but, as of September 2026, there is no final approval and no launch. Do not suggest that an oral orforglipron option can be had now.

For your own reading, look for the full ACHIEVE-2 publication. The points to check are the noninferiority and superiority results, safety and tolerability, and who was enrolled. Keep in mind that none of these reports gives results comparing one oral GLP-1 drug with another. The Dr. Reddy's trial against RYBELSUS® has only been recommended for permission. Current guidelines and the drugs actually available in India remain the practical guide.