Semaglutide, an oral glucagon-like peptide-1 receptor agonist (GLP-1-RA), has been approved for use in type 2 diabetes in India, in daily doses of 3 mg, 7 mg and 14 mg. Injectable semaglutide preparations are used, in varying doses, for the management of both type 2 diabetes and obesity. There has been much interest and curiosity regarding the utility of higher doses of oral semaglutide in obesity care. The much-awaited phase 3 clinical trial PIONEER PLUS has recently reported its top end results.

PIONEER PLUS studied 25 and 50 mg doses of oral semaglutide in patients with type 2 diabetes for a duration of 68 weeks. Oral semaglutide 14 mg was also used as a comparator arm.

The 25 and 50 mg doses showed significant reduction in glycosylated hemoglobin (HbA1c) and weight reduction in comparison to 14 mg of oral semaglutide. As per the treatment policy estimand, 25 mg and 50 mg oral semaglutide showed superior HbA1c reduction of 1.8% and 2% compared with a reduction of 1.5% with oral semaglutide 14 mg. Patients treated with oral semaglutide 25 mg and 50 mg also experienced a superior weight loss of 6.7 kg and 8.0 kg, respectively compared to a weight loss of 4.4 kg with oral semaglutide 14 mg.^1,2

Like the 14 mg dose of oral semaglutide, 25 and 50 mg doses were also safe and well-tolerated. The most common adverse events were gastrointestinal (GI) events, which were transient and mild to moderate in nature.

The interim results declared by Novo Nordisk seem very promising and open the doors for the use of oral semaglutide in higher doses of 25 and 50 mg. If we look at the HbA1c reduction, a greater number of patients can be expected to achieve glycemic targets with higher doses of oral semaglutide.  Therefore, 25 and 50 mg doses can be a therapeutic option for those type 2 diabetes patients who need further glycemic control or weight loss. Detailed data about GI adverse events is awaited.

Based on above data Novo Nordisk plans to file regulatory approval for higher doses of oral semaglutide for treatment intensification.¹

The results need to be viewed from the Indian perspective. A post hoc analysis of tolerability should be carried out in Indian patients. The complete results may be presented at future international conferences or could be published in journals. As we await detailed results, we hope for better outcomes for persons living with diabetes and obesity.

References

1. Oral semaglutide 25 mg and 50 mg demonstrate superior reductions in HbA1c and body weight versus 14 mg in people with type 2 diabetes in the PIONEER PLUS phase 3 trial. Available at: https://www.globenewswire.com/news-release/2023/03/24/2634147/0/en/Oral-semaglutide-25-mg-and-50-mg-demonstrate-superior-reductions-in-HbA1c-and-body-weight-versus-14-mg-in-people-with-type-2-diabetes-in-the-PIONEER-PLUS-phase-3-trial.html. March 24, 2023.
2. Kalra S, Das S, Zargar AH. A review of oral semaglutide available evidence: a new era of management of diabetes with peptide in a pill form. Indian J Endocrinol Metab. 2022 Mar-Apr;26(2):98-105. doi: 10.4103/ijem.ijem_522_21.