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.

Zinman B, Aroda VR, Buse JB, Cariou B, Harris SB, Hoff ST, Pedersen KB, Tarp-Johansen MJ, Araki E

Diabetes care17 Sept 2019Cited by 222 (Europe PMC)

PMID31530667PMCIDPMC7364672DOI10.2337/dc19-0898PepBankPUB-31530667

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study9

9 results from studies that gave the peptide. 9 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide 3 mg reduced HbA1c more than placebo at week 26.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide 3 mg lowered HbA1c more than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 26, 3 mg
Study
n = 368
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3 mg · oral · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−0.5%
3 mg, week 26
Source sentences
Summary
Oral semaglutide was superior to placebo in reducing HbA_1c (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)
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066701
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide 7 mg reduced HbA1c more than placebo at week 26.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide 7 mg lowered HbA1c more than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 26, 7 mg
Study
n = 366
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
7 mg · oral · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−0.9%
7 mg, week 26
Source sentences
Summary
Oral semaglutide was superior to placebo in reducing HbA_1c (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)
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066702
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide 14 mg reduced HbA1c more than placebo at week 26.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide 14 mg lowered HbA1c more than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 26, 14 mg
Study
n = 365
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
14 mg · oral · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−1.2%
14 mg, week 26
Source sentences
Summary
Oral semaglutide was superior to placebo in reducing HbA_1c (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)
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066703
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide 3 mg reduced body weight more than placebo at week 26.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide 3 mg led to more weight loss than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseBody weight change at week 26, 3 mg
Study
n = 368
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
3 mg · oral · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−0.9 kg
3 mg, week 26
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066704
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide 7 mg reduced body weight more than placebo at week 26.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide 7 mg led to more weight loss than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseBody weight change at week 26, 7 mg
Study
n = 366
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
7 mg · oral · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−2 kg
7 mg, week 26
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066705
06HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide 14 mg reduced body weight more than placebo at week 26.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide 14 mg led to more weight loss than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseBody weight change at week 26, 14 mg
Study
n = 365
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
14 mg · oral · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−3.3 kg
14 mg, week 26
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066706
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide reduced HbA1c more than placebo in a dose-dependent way at weeks 26 and 52 under both estimands.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide lowered HbA1c more than placebo, with bigger drops at higher doses.
Peptide
Semaglutide
Outcome
DecreaseHbA1c reduction at weeks 26 and 52, both estimands
Study
n: not reported in source
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3, 7 and 14 mg · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
Significantly greater dose-dependent HbA_1c and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066707
08HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on insulin, oral semaglutide reduced body weight more than placebo in a dose-dependent way at weeks 26 and 52 under both estimands.
In plain wordsIn adults with type 2 diabetes on insulin, oral semaglutide led to more weight loss than placebo, with bigger losses at higher doses.
Peptide
Semaglutide
Outcome
DecreaseBody weight reduction at weeks 26 and 52, both estimands
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
3, 7 and 14 mg · oral · 52 weeksAs given in this study (human).
Source sentences
Summary
Significantly greater dose-dependent HbA_1c and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066708
09HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes on insulin, nausea was the most frequent adverse event with oral semaglutide, in 11.4-23.2% of patients versus 7.1% with placebo.
In plain wordsIn adults with type 2 diabetes on insulin, nausea occurred in 11.4-23.2% on oral semaglutide, against 7.1% on placebo.
Peptide
Semaglutide
Outcome
IncreaseNausea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
3, 7 and 14 mg · oral · 52 weeksAs given in this study (human).
Measurements
Nausea incidence
11.4 to 23.2%
oral semaglutide
Nausea incidence
7.1%
placebo
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Report a problemFND-3153066709

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03021187

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin

Novo Nordisk A/Sn = 7312 Feb 2017 to 22 Aug 2018

Diabetes · Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 2 Mar 2020

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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