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Diabetes Care. 2019 Sep 17. pii: dc190898. doi: 10.2337/dc19-0898. [Epub ahead of print]

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial.

Author information

1
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada zinman@lunenfeld.ca.
2
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
3
MedStar Health Research Institute, Hyattsville, MD.
4
Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC.
5
Department of Endocrinology, L'Institut du Thorax, CIC INSERM 1413, CHU Nantes, UNIV Nantes, Nantes, France.
6
Department of Family Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
7
Novo Nordisk A/S, Søborg, Denmark.
8
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

OBJECTIVE:

To investigate the efficacy, safety, and tolerability of oral semaglutide added to insulin with or without metformin.

RESEARCH DESIGN AND METHODS:

Patients with type 2 diabetes uncontrolled on insulin with or without metformin were randomized to oral semaglutide 3 mg (N = 184), 7 mg (N = 182), or 14 mg (N = 181) or to placebo (N = 184) in a 52-week, double-blind trial. End points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients.

RESULTS:

Oral semaglutide was superior to placebo in reducing HbA1c (estimated treatment difference [ETD] -0.5% [95% CI -0.7, -0.3%], -0.9% [-1.1, -0.7%], -1.2% [-1.4, -1.0%] for 3, 7, and 14 mg, respectively; P < 0.001) and body weight (ETD -0.9 kg [95% CI -1.8, -0.0 kg], -2.0 kg [-3.0, -1.0 kg], -3.3 kg [-4.2, 2.3 kg]; P = 0.0392 for 3 mg, P ≤0.0001 for 7 and 14 mg) at week 26 (treatment policy estimand). Significantly greater dose-dependent HbA1c and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands). The most frequent adverse event with oral semaglutide was nausea (11.4-23.2% of patients vs. 7.1% with placebo; mostly mild to moderate).

CONCLUSIONS:

Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin with or without metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-like peptide 1 receptor agonists.

PMID:
31530667
DOI:
10.2337/dc19-0898

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