A phase IIIa trial (PIONEER 5) reports with oral semaglutide in adults with type 2 diabetes and moderate renal impairment.- Novo Nordisk.

Novo Nordisk announced the headline results from PIONEER 5, a phase IIIa trial with oral semaglutide in adults with type 2 diabetes and moderate renal impairment. Oral semaglutide is an investigational GLP-1 analogue taken once daily as a tablet. The 26-week trial investigated the efficacy and safety of 14 mg oral semaglutide compared with placebo in 324 people with type 2 diabetes and moderate renal impairment inadequately controlled with metformin, sulfonylurea alone or in combination with metformin, or basal insulin alone or in combination with metformin.

Two distinct statistical approaches to evaluating the effects of oral semaglutide were applied in the PIONEER 5 trial; a primary statistical approach required by recent regulatory guidance evaluating the effect regardless of discontinuation of treatment and use of rescue medication, and a secondary statistical approach describing the effect while on treatment and without use of rescue medication. The trial achieved its primary objective according to the primary statistical approach by demonstrating statistically significant and superior reductions in HbA1c with oral semaglutide compared to placebo at week 26. Furthermore, people treated with oral semaglutide achieved statistically significant and superior reductions in body weight compared to placebo at week 26. When applying the secondary statistical approach, people treated with oral semaglutide experienced a statistically significantly greater reduction in HbA1c of 1.1% compared to 0.1% with placebo. Reduction in body weight was statistically significantly greater with oral semaglutide at week 26, with a reduction of 3.7 kg compared to 1.1 kg with placebo. From a baseline HbA1c of 8.0%, the proportion of people achieving the American Diabetes Association (ADA) target of HbA1c below 7.0% was statistically significantly greater with 14 mg oral semaglutide, with 64% achieving the target at week 26, compared to 21% with placebo.

In this 26-week trial, oral semaglutide was well-tolerated in people with moderate renal impairment, with a profile consistent with GLP-1-based therapies. The most common adverse event for oral semaglutide was mild to moderate nausea. In PIONEER 5, 19% of people treated with oral semaglutide experienced nausea, compared to 8% of people treated with placebo. The proportion of people who discontinued treatment due to adverse events was 15% for people treated with oral semaglutide compared to 6% with placebo.