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
Top Cited Papers
Open Access
- 10 July 2019
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 42 (12), 2262-2271
- https://doi.org/10.2337/dc19-0898
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], and –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], −2.0 kg [−3.0, −1.0], and −3.3 kg [−4.2, −2.3]; 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.Keywords
This publication has 28 references indexed in Scilit:
- Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study)Diabetes Care, 2016
- Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trialsBMC Endocrine Disorders, 2016
- GLP-1 RAs as compared to prandial insulin after failure of basal insulin in type 2 diabetes: lessons from the 4B and Get-Goal DUO 2 trialsDiabetes & Metabolism, 2015
- Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo‐controlled trialDiabetes, Obesity and Metabolism, 2015
- Contribution of Liraglutide in the Fixed-Ratio Combination of Insulin Degludec and Liraglutide (IDegLira)Diabetes Care, 2014
- Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysisBMJ, 2013
- Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta‐analysisDiabetes, Obesity and Metabolism, 2012
- Graphical approaches for multiple comparison procedures using weighted Bonferroni, Simes, or parametric testsBiometrical Journal, 2011
- Addressing barriers to initiation of insulin in patients with type 2 diabetesPrimary Care Diabetes, 2010
- Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 DiabetesThe New England Journal of Medicine, 2007