SAN FRANCISCO — As an add-on to insulin therapy in individuals with uncontrolled type 2 diabetes, oral semaglutide reduced hemoglobin A1c (HbA1c) and body weight better than placebo at week 26 and was well-tolerated, without significant increases in hypoglycemia rates, according to research results presented at the American Diabetes Association 79th Scientific Sessions, held June 7 to 11, 2019, in San Francisco, California.
In this 52-week double-blind placebo-controlled trial (PIONEER 8; ClinicalTrials.gov Identifier: NCT03021187), patients with type 2 diabetes uncontrolled on insulin with/without metformin were randomly assigned to receive oral semaglutide or placebo (semaglutide 3 mg, n = 184; 7 mg, n = 182; 14 mg, n = 181; placebo, n = 184). For weeks 0 through 26, total daily insulin was reduced by an optional 20% and capped at baseline level, then was freely adjustable for weeks 26 through 52. Study end points were change from baseline to week 26 in HbA1c and body weight, and scientific questions were addressed by 2 estimands for all participants: a treatment policy estimand (regardless of rescue medication use or trial product discontinuation) and a trial product estimand (on trial product without rescue medication use).
Oral semaglutide was superior to placebo in reducing body weight and HbA1c at week 26, answering the treatment policy estimand. Results also showed significantly greater and dose-dependent body weight and HbA1c reductions compared with placebo at weeks 26 and 52, answering both estimands.
Total daily dose of insulin was significantly reduced from baseline with oral semaglutide compared with placebo at week 26 (except for semaglutide 3 mg) and week 52. The semaglutide and placebo groups showed similar rates of hypoglycemia. The most prevalent adverse event with oral semaglutide was nausea (11.4% to 23.2% vs 7.1% with placebo), and 7.1% to 13.3% of participants prematurely discontinued due to adverse events compared with only 2.7% receiving placebo.
Study investigators concluded that “oral [semaglutide] had superior HbA1c and [body weight] reductions vs. [placebo] at week 26. It also reduced insulin use by week 52 and was well tolerated without significantly increasing hypoglycemia rate.”
Disclosures: Multiple study investigators disclosed associations with pharmaceutical companies. Please see the original reference for a full list of disclosures.
Zinman B, Aroda VR, Buse JB, et al. Oral semaglutide as add-on to insulin in T2D: PIONEER 8. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. Poster 985-P.