New daily pill can replace injectable weight-loss drugs, show early results

This is significant as it raises hopes of an effective and easy-to-use treatment in a market that currently relies heavily on weight loss injections. Injectable GLP-1 drugs became available in India only earlier this year.

Why is the trial important?

One of the biggest challenges of taking injectables is the hassle of getting the once-weekly shot. With the ease-of-use, an oral regimen is likely to make the drugs more accessible.

“The drug helped over 65 per cent of participants reach healthy HbA1C levels (average blood sugar counts of three months) with mainly mild side effects and excellent adherence. No liver safety issues were observed, unlike Pfizer’s recently abandoned oral obesity drug. While this represents progress, cost and accessibility concerns remain, especially in markets like India where oral GLP-1 receptor analogues are already available,” says Dr Anoop Misra, chairman, Fortis CDOC for Endocrinology and Diabetes.

How effective is the drug?

A phase 3 trial showed that type 2 diabetes patients on Orforglipron lost 16 pounds, or nearly 8% of their body weight, over 40 weeks. “Levels of HbA1c, or average blood sugar count over three months, fell by an average of 1.3% to 1.6% across doses. After 40 weeks of treatment in the multi-dose trial, orforglipron showed body weight reductions of 4.7% at 3 mg, 6.1% with 12 mg, and 7.9% with 36 mg. Patients on placebo lost 1.6%. This efficacy seems good for an oral pill,” says Dr V Mohan, Chairman, Dr Mohan’s Diabetes Specialities Centre, Chennai.

“Although we cannot compare the effects with more advanced injectables that are expected to hit the market, this could be a good option for those who do not want injections,” he adds.

How does it compare to other oral GLP-1 drugs?

When it comes to oral semaglutide, the OASIS-1 trial showed that it led to a 15.1% reduction in body weight. But this was at the highest 50 mg dose and at 68 weeks, meaning a higher dose and duration as compared to the current Orforglipron trial.

“The Danish company Novo Nordisk had already introduced the first oral semaglutide called Rybelsus, which is being used in India, is safe and helps to reduce weight as well as blood sugar levels. The advantage of Rybelsus is that it is the world’s first ‘peptide (amino acids) in a pill’ and was developed by a revolutionary breakthrough technology. However, Orforglipron is a chemically synthesised, small-molecule drug. So there will be differences in how they are absorbed and taken. So one has to see the results long-term,” says Dr Mohan.

Orforglipron, being a small molecule, is absorbed more easily and doesn’t require the same dietary restrictions as Rybelsus, which is a peptide. Rybelsus needs to be taken on an empty stomach and with water, with specific timing restrictions.

What about safety?

Eli Lilly claims Orforglipron’s safety profile was consistent with other GLP-1s. “The trial found that 13% to 18% of patients given the drug experienced nausea across doses, compared with 2% on placebo. The rate for diarrhoea was 19% to 26% and vomiting 5% to 14%. But long-term tolerability has to be studied,” says Dr K P Singh, Director, Endocrinology, Fortis Hospital, Mohali.