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Diabetes Care. 2019 Sep;42(9):1724-1732. doi: 10.2337/dc19-0749. Epub 2019 Jun 11.

PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes.

Author information

1
Brigham and Women's Hospital, Harvard Medical School, Boston, MA varoda@bwh.harvard.edu.
2
MedStar Health Research Institute, Hyattsville, MD.
3
Dallas Diabetes Research Center at Medical City, Dallas, TX.
4
Yokohama City University, Yokohama, Japan.
5
Division of Endocrinology Metabolism Diabetes, Department of Internal Medicine, Sisli Hamidiye Etfal Teaching and Research Hospital, University of Health Sciences, Istanbul, Turkey.
6
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
7
Cardiometabolic Research Center, Aguascalientes, Mexico.
8
Novo Nordisk A/S, Søborg, Denmark.

Abstract

OBJECTIVE:

This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 (GLP-1) receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed by diet and exercise alone. Two estimands addressed two efficacy-related questions: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a trial product estimand (on trial product without rescue medication use) in all randomized patients.

RESEARCH DESIGN AND METHODS:

This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries. Adults with type 2 diabetes insufficiently controlled with diet and exercise were randomized (1:1:1:1) to once-daily oral semaglutide 3 mg, 7 mg, 14 mg, or placebo. The primary end point was change from baseline to week 26 in HbA1c. The confirmatory secondary end point was change from baseline to week 26 in body weight.

RESULTS:

In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA1c 8.0% [64 mmol/mol]), oral semaglutide reduced HbA1c (placebo-adjusted treatment differences at week 26: treatment policy estimand, -0.6% [3 mg], -0.9% [7 mg], and -1.1% [14 mg]; trial product estimand, -0.7% [3 mg], -1.2% [7 mg], and -1.4% [14 mg]; P < 0.001 for all) and body weight (treatment policy, -0.1 kg [3 mg], -0.9 kg [7 mg], and -2.3 kg [14 mg, P < 0.001]; trial product, -0.2 kg [3 mg], -1.0 kg [7 mg, P = 0.01], and -2.6 kg [14 mg, P < 0.001]). Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide. Trial product discontinuations occurred in 2.3-7.4% with oral semaglutide and 2.2% with placebo.

CONCLUSIONS:

In patients with type 2 diabetes, oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA1c (all doses) and body weight loss (14 mg dose) versus placebo, with a safety profile consistent with other GLP-1 receptor agonists.

PMID:
31186300
DOI:
10.2337/dc19-0749

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