Elicit: GLP-1 and Anxiety: Clinical Insights (public)
GLP-1 and Anxiety: Clinical Insights (public)
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September 11, 2025
Clinical studies evaluating the effects of GLP-1 on anxiety
Clinical studies of GLP-1 agents measured anxiety only as secondary outcomes using indirect methods rather than dedicated anxiety scales, with results showing modest changes that do not support a clear direct effect on anxiety.
Abstract
GLP-1 agent studies in patients with type 2 diabetes, overweight/obesity, or cardiovascular disease provide only indirect insights into anxiety outcomes. None of the five trials employed dedicated, validated anxiety scales. Instead, anxiety was measured as a subdomain of general quality‐of‐life instruments (including SF-36v2, DTR-QoL, EQ-5D/EQ-5D-5L, and TRIM-D) or recorded as infrequent neuropsychiatric adverse events.
- In one trial, DTR-QoL anxiety scores increased by 12.9 (SD 20.8) with an insulin degludec/liraglutide combination versus 0.4 (SD 17.2) with insulin degludec alone.
- Another trial reported an EQ-5D Visual Analog Scale improvement of +2.83 with albiglutide compared to +1.36 with placebo (p < 0.001).
- Where systematically documented, anxiety or anxiety disorder adverse events occurred in 0.1–0.8% of participants.
The studies consistently measured anxiety only as a secondary or adverse outcome, and the modest changes and low event rates do not support a clear, direct effect of GLP-1 agents on anxiety.
Methods
We analyzed 5 sources from an initial pool of 18, using 7 screening criteria. Each paper was reviewed for 6 key aspects that mattered most to the research question. More on methods
Papers identified with Elicit search
n = 18
Papers screened using: Human Participants, GLP-1 Intervention, Anxiety Outcomes, Study Design, GLP-1 Effect Attribution, Publication Type, Intervention Focus
n = 18
Papers screened out
n = 13
Papers included for extraction
n = 5
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Paper search
Using your research question “Clinical studies evaluating the effects of GLP-1 on anxiety”, we searched across all trials from the ClinicalTrials.gov corpus. We retrieved the 18 trials most relevant to the query.
Screening
We screened in sources based on their abstracts that met these criteria:
- Human Participants: Does this study involve human participants of any age?
- GLP-1 Intervention: Does this study involve administration of GLP-1 receptor agonists (e.g., exenatide, liraglutide, semaglutide, dulaglutide) or native GLP-1?
- Anxiety Outcomes: Does this study measure anxiety as a primary or secondary outcome using validated instruments OR report anxiety-related adverse events with quantifiable data?
- Study Design: Is this study a randomized controlled trial, cohort study, case-control study, cross-sectional study, case series with 3 or more participants, systematic review, or meta-analysis?
- GLP-1 Effect Attribution: Can the effects of GLP-1 on anxiety be isolated or clearly attributed to the GLP-1 intervention (rather than confounded by other simultaneous interventions)?
- Publication Type: Is this a peer-reviewed original research study with sufficient methodological detail (not a conference abstract, editorial, commentary, or opinion piece without original data)?
- Intervention Focus: Does this study focus on GLP-1 agonists or native GLP-1 (rather than focusing solely on GLP-1 antagonists or inhibitors)?
We considered all screening questions together and made a holistic judgement about whether to screen in each paper.
Data extraction
We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.
- Study Design Type:
Identify the specific type of study design from the full text. Look in the methods section for precise description. Possible types include:
- Randomized controlled trial
- Observational study
- Crossover study
- Parallel group study
If multiple design elements are present, list all. If unclear, note “design not clearly specified”. Prioritize the most specific design description available.
- Intervention Details Related to GLP-1:
Extract specific details about GLP-1 related intervention:
- Specific GLP-1 medication used (e.g., semaglutide, liraglutide)
- Dosage
- Route of administration
- Frequency of administration
- Duration of intervention
Be precise about numerical values. If ranges are provided, record the full range. If multiple intervention arms exist, extract details for each arm separately.
- Participant Demographics:
Extract key demographic information:
- Total sample size
- Age range or mean age
- Gender distribution
- Specific medical conditions or inclusion/exclusion criteria
- Geographic location of study
If percentages or means are provided, record them. If ranges are given, note the full range. If subgroup analyses exist, note those details.
- Anxiety Measurement Methods:
Identify and extract:
- Specific anxiety measurement tools used (e.g., HAM-A, STAI)
- Timing of anxiety assessments
- Primary vs secondary outcome status
- Specific anxiety-related metrics measured
Record exact names of measurement tools. If multiple tools were used, list all. If scoring methods are described, include those details.
- Anxiety-Related Outcomes:
Extract quantitative anxiety outcomes:
- Mean anxiety scores
- Standard deviations
- Statistical significance of anxiety-related findings
- Effect sizes if reported
Prioritize primary outcome data. If multiple time points exist, extract data from each. Note any statistical adjustments or confounding factors considered.
- Study Limitations and Potential Biases:
Extract information about:
- Funding sources
- Potential conflicts of interest
- Limitations acknowledged by authors
- Dropout rates
- Blinding procedures
If multiple limitations are mentioned, list comprehensively. Look specifically in discussion/limitations sections of the full text.
Results
Characteristics of Included Studies
Study Identifier
GLP-1 Agent(s)
Population
Primary Outcomes
Duration
NCT03015220
Semaglutide (oral, 3/7/14 mg daily), Dulaglutide (0.75 mg weekly)
Japanese adults with type 2 diabetes (n=458), mean age 58, 74.5% male, all Asian
Glycemic control, safety
52 weeks\
NCT02911948
Insulin degludec/liraglutide (fixed-ratio), Insulin degludec
Japanese adults with type 2 diabetes inadequately controlled on insulin (n=210), mean age 56, 63.3% male, all Asian
Glycemic control, safety
26 weeks\
NCT01644500
Dulaglutide (0.75, 1.5 mg weekly), Glimepiride
Asian adults with type 2 diabetes (n=737), mean age 52.8, 55.4% male, all Asian
Glycemic control, safety
26 weeks\
NCT03574597
Semaglutide (dose not specified, weekly)
Adults with overweight/obesity and prior cardiovascular disease (n=17,604), mean age 61.6, 72.3% male, 84% White
Major adverse cardiovascular events
2.5–5 years\
NCT02465515
Albiglutide (30–50 mg weekly)
Adults with type 2 diabetes and established cardiovascular disease (n=9,463), mean age 64.1, 69.4% male, 85% White
Major adverse cardiovascular events
Median 1.65 years\
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Key characteristics across studies:
- GLP-1 agents studied:
- Semaglutide (oral and injectable) in 2 studies
- Dulaglutide (injectable) in 2 studies
- Liraglutide (as part of a fixed-ratio with insulin) in 1 study
- Albiglutide in 1 study
- One study directly compared two GLP-1 agents (oral semaglutide vs. dulaglutide)
- One study evaluated a fixed-ratio GLP-1/insulin combination
- In two studies, the comparator was not a GLP-1 agent (glimepiride, insulin degludec)
- Population:
- Four studies included adults with type 2 diabetes (three exclusively, one with established cardiovascular disease)
- One study included adults with overweight/obesity and prior cardiovascular disease
- Three studies were conducted exclusively in Japanese or Asian populations
- Two studies were global, with the majority of participants being White (84–85%)
- Three studies had sample sizes under 1,000; two studies had sample sizes over 1,000
- Primary outcomes:
- Glycemic control and safety in three studies
- Major adverse cardiovascular events in two studies
- Duration:
- Two studies: less than 1 year (26 weeks)
- One study: 1 year (52 weeks)
- One study: between 1 and 2 years (median 1.65 years)
- One study: greater than 2 years (2.5–5 years)
Effects
Direct Anxiety Outcomes
No study used a dedicated, validated anxiety scale (such as the Hamilton Anxiety Rating Scale, State-Trait Anxiety Inventory, or Generalized Anxiety Disorder-7) as a primary or secondary outcome. Anxiety-related outcomes were assessed only indirectly, via subdomains of general quality of life instruments or as adverse events.
Study
Anxiety Measurement Tool(s)
Timing
Primary/Secondary Outcome
Quantitative Results
Statistical Significance/Effect Size
NCT03015220
Short Form-36 version 2 (SF-36v2, mental health), Diabetes Therapy-Related Quality of Life (DTR-QoL, anxiety/dissatisfaction)
Weeks 26, 52
Secondary
SF-36v2 mental health: changes from baseline ranged from -1.64 to +0.27; DTR-QoL anxiety: changes from +0.98 to +12.24
No mention found\
NCT02911948
DTR-QoL (anxiety/dissatisfaction), EuroQol 5-Dimension 5-Level (EQ-5D-5L, anxiety/depression)
Weeks 0, 26
Secondary
DTR-QoL anxiety: +12.9 (SD 20.8) with degludec/liraglutide vs. +0.4 (SD 17.2) with degludec; EQ-5D-5L index: +0.02 (SD 0.08) vs. -0.01 (SD 0.11)
No mention found\
NCT01644500
EQ-5D (anxiety/depression)
Week 26
Secondary
Most participants reported “no problems” (208–214 per group); “some problems” in 7–17 per group; “extreme problems” in none
No mention found\
NCT03574597
EQ-5D-5L (anxiety/depression)
Weeks 0, 104
Secondary
No mention found quantitatively; only as adverse events
No mention found\
NCT02465515
EQ-5D (anxiety/depression), Treatment-Related Impact Measure for Diabetes (TRIM-D, psychological health)
Baseline, months 8, 16
Secondary
EQ-5D Visual Analog Scale (VAS): +2.83 (albiglutide) vs. +1.36 (placebo) at 8 months; TRIM-D psychological health: +6.92 (albiglutide) vs. +4.53 (placebo) at 8 months
EQ-5D VAS: p<0.001 at 8 months; TRIM-D: p<0.001 at 8 months\
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Patterns in anxiety measurement and reporting:
- Measurement tools used:
- Diabetes Therapy-Related Quality of Life (DTR-QoL): 2 studies
- EuroQol 5-Dimension (EQ-5D): 2 studies
- EuroQol 5-Dimension 5-Level (EQ-5D-5L): 2 studies
- Short Form-36 version 2 (SF-36v2): 1 study
- Treatment-Related Impact Measure for Diabetes (TRIM-D): 1 study
- Some studies used more than one tool
- Quantitative anxiety results:
- Quantitative results were found for 4 studies
- DTR-QoL anxiety scores: 2 studies
- EQ-5D or EQ-5D-5L anxiety/depression: 2 studies
- SF-36v2 mental health and TRIM-D psychological health: each in 1 study
- One study (NCT01644500) reported proportions of participants with “no problems” or “some problems” on EQ-5D, rather than mean changes
- No mention found of quantitative anxiety results for 1 study
- Quantitative results were found for 4 studies
- Statistical significance or effect size:
- Statistical significance (p-values) for anxiety-related outcomes was found in 1 study (NCT02465515, p<0.001 for both EQ-5D VAS and TRIM-D)
- No mention found of statistical significance or effect size reporting for the other 4 studies
Summary of direct anxiety outcomes:
- No study used a dedicated, validated anxiety scale.
- Anxiety was assessed only as a subdomain of general quality of life instruments or as an adverse event.
- Where measured, changes in anxiety-related domains were small and not robustly tested for statistical significance, except in one study.
- The most commonly used tools for anxiety-related domains were DTR-QoL and EQ-5D/EQ-5D-5L (each in 2 studies).
Neuropsychiatric Adverse Events
Study
GLP-1 Agent
Reported Neuropsychiatric Events
Frequency
NCT03015220
Semaglutide, Dulaglutide
No mention found of systematic reporting; no anxiety-specific adverse events noted
No mention found\
NCT02911948
Insulin degludec/liraglutide
No mention found of systematic reporting; no anxiety-specific adverse events noted
No mention found\
NCT01644500
Dulaglutide
Anxiety: 2 (0.8%) in 1.5 mg group, 1 (0.4%) in 0.75 mg group, 2 (0.8%) in glimepiride group; Anxiety disorder: 1 (0.4%) in 1.5 mg group
Rare\
NCT03574597
Semaglutide
Anxiety: 6 (0.1%) semaglutide, 3 (0.0%) placebo; Anxiety disorder: 1 (0.0%) semaglutide, 0 placebo; Mixed anxiety/depressive disorder: 0 semaglutide, 2 (0.0%) placebo
Very rare\
NCT02465515
Albiglutide
No mention found of systematic reporting; no anxiety-specific adverse events noted
No mention found\
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Key findings on neuropsychiatric adverse events:
- Systematic reporting:
- Systematic reporting of anxiety-specific neuropsychiatric events was found in 2 out of 5 studies
- The other 3 studies did not systematically report these events and did not note any anxiety-specific adverse events
- Frequency of events:
- In the 2 studies with systematic reporting, anxiety or anxiety disorder events were rare or very rare:
- One study reported anxiety events as rare (0.4–0.8% incidence)
- One study reported anxiety events as very rare (≤0.1% incidence)
- No mention found of frequency information for the other 3 studies
- In the 2 studies with systematic reporting, anxiety or anxiety disorder events were rare or very rare:
- Summary:
- Among studies that systematically reported anxiety-specific neuropsychiatric events, these events were rare or very rare
- The majority of studies did not systematically report on these events, limiting interpretability
Indirect Effects Potentially Relevant to Anxiety
Several studies reported small improvements in general psychological health or mental health domains of quality of life instruments with GLP-1 agents compared to placebo or active comparators.
Examples from included studies:
- In NCT02911948, the DTR-QoL anxiety domain improved more with degludec/liraglutide than with degludec alone, though without statistical testing.
- In NCT02465515, the TRIM-D psychological health domain improved more with albiglutide than with placebo, with statistical significance at 8 months.
- These effects were modest and not specific to anxiety.
Interpretation of indirect effects:
- Improvements in psychological health domains may reflect overall health benefits or improved diabetes control, rather than a direct anxiolytic effect of GLP-1 agents.
- The lack of dedicated anxiety measurement and the small magnitude of changes limit interpretability of these findings.
Summary
- Absence of direct evidence:
- The available studies did not use dedicated, validated anxiety measures as primary or secondary outcomes.
- Anxiety-related outcomes were assessed only as subdomains of general quality of life instruments or as rare adverse events.
- Magnitude and significance of effects:
- Where measured, changes in anxiety-related domains were small.
- Statistical significance was only reported in one study, and only for general psychological health domains, not for anxiety specifically.
- Adverse events:
- Neuropsychiatric adverse events, including anxiety, were rare or very rare in studies that systematically reported them.
- Most studies did not systematically report on anxiety-specific adverse events.
- Limitations of the evidence base:
- The evidence is limited by the lack of dedicated anxiety assessment and the indirect nature of available data.
- The findings do not provide clear evidence for or against an effect of GLP-1 agents on anxiety.
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NCT03015220: Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes
Lead Sponsor: Novo Nordisk A/S, Sponsor: None
NIH·
2021·
Citations unknown
ClinicalTrials
Study Design Type
Randomized controlled trial with parallel group design
The study is specifically described as having RANDOMIZED allocation with a PARALLEL intervention model. It is classified as an INTERVENTIONAL study type with no masking (open-label), confirming this is both a randomized controlled trial and uses a parallel group study design.
Intervention Details Related to GLP-1
GLP-1 Interventions:
Semaglutide: - Medication: Semaglutide - Dosages: 3 mg, 7 mg, 14 mg - Route of administration: Oral administration - Frequency of administration: Once-daily - Duration of intervention: 52-week treatment period
Dulaglutide: - Medication: Dulaglutide - Dosage: 0.75 mg - Route of administration: Subcutaneously administration (s.c., under the skin) - Frequency of administration: Once-weekly - Duration of intervention: 52-week treatment period
Both medications were administered as add-on to pre-trial oral antidiabetic drug (OAD).
Participant Demographics
Total Sample Size: - 458 participants (actual enrollment)
Age Demographics: - Minimum age: 20 years - Mean age: 58 years (standard deviation 10 years) across all participants - Individual treatment group means: Oral Semaglutide 3 mg: 59 (10), 7 mg: 58 (11), 14 mg: 57 (10), Dulaglutide: 61 (9)
Gender Distribution: - Females: 117 participants (25.5%) - Males: 341 participants (74.5%) - All sexes eligible
Race and Ethnicity: - All participants were Asian: 458/458 (100%) - All participants were Not Hispanic or Latino: 458/458 (100%)
Medical Conditions: - Japanese subjects with type 2 diabetes - Diagnosed with type 2 diabetes mellitus for at least 60 days prior to screening - HbA1c levels between 7.0%-10.5% (53-91 mmol/mol)
Geographic Location: - Study conducted in Japan with 34 locations - Sites distributed across multiple Japanese cities and prefectures including Tokyo, Osaka, Sapporo, and other regions
Anxiety Measurement Methods
Not mentioned - This trial focused on safety and efficacy of diabetes medications and did not include any specific anxiety measurement tools. While the study included quality of life assessments (SF-36v2 Health Survey and DTR-QoL questionnaire) that have some mental health components, no dedicated anxiety measurement instruments such as HAM-A, STAI, GAD-7, or other clinical anxiety scales were used as outcome measures.
Anxiety-Related Outcomes
Anxiety-related outcomes were assessed through two quality of life instruments in this trial:
SF-36v2 Mental Health Domain (change from baseline, mean [SD]): Week 26: Oral semaglutide 3mg: -1.03 (6.54), Oral semaglutide 7mg: 0.16 (6.66), Oral semaglutide 14mg: -0.41 (7.32), Dulaglutide 0.75mg: 0.27 (7.34) Week 52: Oral semaglutide 3mg: -1.64 (7.63), Oral semaglutide 7mg: -0.35 (6.68), Oral semaglutide 14mg: 0.27 (7.58), Dulaglutide 0.75mg: -0.31 (10.24)
SF-36v2 Mental Component Summary (change from baseline, mean [SD]): Week 26: Oral semaglutide 3mg: -1.13 (6.54), Oral semaglutide 7mg: -0.07 (5.85), Oral semaglutide 14mg: -0.71 (5.91), Dulaglutide 0.75mg: -0.42 (6.04) Week 52: Oral semaglutide 3mg: -1.52 (7.26), Oral semaglutide 7mg: -0.19 (6.31), Oral semaglutide 14mg: -0.23 (6.15), Dulaglutide 0.75mg: -0.74 (8.57)
DTR-QoL Anxiety and Dissatisfaction with Treatment Domain (change from baseline, mean [SD]): Week 26: Oral semaglutide 3mg: 6.54 (18.08), Oral semaglutide 7mg: 10.94 (17.83), Oral semaglutide 14mg: 12.24 (17.41), Dulaglutide 0.75mg: 9.24 (20.87) Week 52: Oral semaglutide 3mg: 0.98 (18.60), Oral semaglutide 7mg: 9.93 (19.61), Oral semaglutide 14mg: 11.37 (18.68), Dulaglutide 0.75mg: 3.14 (19.79)
No statistical significance testing, effect sizes, or statistical adjustments were reported for these anxiety-related outcomes. The SF-36 scores use norm-based scoring where positive changes indicate improvement, while DTR-QoL scores range 0-100 with higher scores indicating better outcomes (less anxiety).
Study Limitations and Potential Biases
Funding Sources: - Sponsored by Novo Nordisk A/S, a pharmaceutical company that manufactures semaglutide, the primary investigational drug being tested
Potential Conflicts of Interest: - Principal investigator was not a sponsor employee, reducing direct conflicts - However, funding by drug manufacturer (Novo Nordisk A/S) represents inherent potential conflict as study contact organization is Novo Nordisk A/S
Study Design Limitations: - Open-label design with no masking/blinding, which could introduce bias in outcome assessment and participant behavior since both investigators and patients knew which treatment was being administered
Dropout Rates: - Low overall dropout rates with 10 total participants not completing across all groups: 3 (semaglutide 3mg), 2 (semaglutide 7mg), 3 (semaglutide 14mg), 2 (dulaglutide) - Most discontinuations were voluntary subject withdrawals rather than protocol violations - Minimal loss to follow-up with only 1 participant lost in the semaglutide 14mg group
Author-Acknowledged Limitations: Not mentioned (no discussion or limitations section is provided in this clinical trial registry document)
Note: This analysis is based on the clinical trial registry information provided. A comprehensive assessment of study limitations would typically require access to the full published manuscript with discussion and limitations sections.
Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes (NCT03015220)
Summary
- Status: COMPLETED
- Study Type: INTERVENTIONAL
- Phase: PHASE3
- Allocation: RANDOMIZED
- Intervention Model: PARALLEL
- Primary Purpose: TREATMENT
- Masking: NONE
- Enrollment: 458 participants (ACTUAL)
- Start Date: 2017-01-10
- Primary Completion Date: 2018-07-12
- Completion Date: 2018-07-12
- First Posted: 2017-01-09
- Results First Posted: 2019-12-30
- Last Update Posted: 2021-03-02
- Sponsor: Novo Nordisk A/S
This trial is conducted in Asia. The aim of this trial is to investigate Safety and efficacy of oral semaglutide versus dulaglutide both in combination with one OAD (oral antidiabetic drug) in Japanese subjects with type 2 diabetes.
Conditions & Interventions
Conditions (2)
- Diabetes
- Diabetes Mellitus, Type 2
Interventions (2)
| Type | Name | Description | Arms |
|---|---|---|---|
| DRUG | Semaglutide | Oral administration once-daily, as add-on to pre-trial oral antidiabetic drug (OAD). | Oral semaglutide 14 mg, Oral semaglutide 3 mg, Oral semaglutide 7 mg |
| DRUG | Dulaglutide | Subcutaneously administration (s.c., under the skin) once-weekly, as add-on to pre-trial oral antidiabetic drug (OAD). | Dulaglutide 0.75 mg |
Eligibility
- Age: Minimum: 20 Years
- Sex: ALL
- Accepts Healthy Volunteers: No
Eligibility Criteria
Inclusion Criteria:
- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
- Japanese male or female, age above or equal to 20 years at the time of signing informed consent
- Diagnosed with type 2 diabetes mellitus for at least 60 days prior to day of screening
- HbA1c (glycosylated haemoglobin) between 7.0%-10.5% (53-91 mmol/mol) (both inclusive)
- OAD (oral antidiabetic drug) monotherapy with stable daily dose for at least 60 days prior to the day of screening of one of SU (sulphonylurea) glinide , TZD (thiazolidinedione), α-GI (alpha-glucosidase inhibitor) or SGLT-2 (sodium-glucose cotransporter-2) inhibitor according to Japanese labelling
Exclusion Criteria:
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives
- Any disorder, which in the investigator’s opinion might jeopardise subject’s safety or compliance with the protocol
- Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC)
- History of pancreatitis (acute or chronic)
- History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
- Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack (TIA) within the past 180 days prior to the day of screening and randomisation
- Subjects presently classified as being in New York Heart Association (NYHA) Class IV
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Subjects with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL)
- Renal impairment defined as estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)
- Treatment with once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) or once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor in a period of 90 days before the day of screening
- For subjects treated with an OAD other than TZD at screening: Treatment with TZD in a period of 90 days before the day of screening
- Treatment with any medication for the indication of diabetes or obesity in addition to background OAD medication (SU, glinide, TZD, α-GI or SGLT-2 inhibitor) in a period of 60 days before the day of screening with the exception of short-term insulin treatment for acute illness for a total of at least 14 days
- Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
- History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in situ carcinomas)
- History of diabetic ketoacidosis
Locations (34)
Countries: Japan (34)
| Facility | City | State/Province | Country | Status |
|---|---|---|---|---|
| Novo Nordisk Investigational Site | Adachi-ku, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Annaka-shi, Gunma | — | Japan | — |
| Novo Nordisk Investigational Site | Arakawa-ku, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Chiba-shi, Chiba | — | Japan | — |
| Novo Nordisk Investigational Site | Chuo-ku, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Fukushima | — | Japan | — |
| Novo Nordisk Investigational Site | Gunma | — | Japan | — |
| Novo Nordisk Investigational Site | Ibaraki | — | Japan | — |
| Novo Nordisk Investigational Site | Iruma-shi, Saitama | — | Japan | — |
| Novo Nordisk Investigational Site | Kanagawa | — | Japan | — |
| Novo Nordisk Investigational Site | Kashiwara-shi, Osaka | — | Japan | — |
| Novo Nordisk Investigational Site | Kawagoe-shi, Saitama | — | Japan | — |
| Novo Nordisk Investigational Site | Kawaguchi-shi, Saitama | — | Japan | — |
| Novo Nordisk Investigational Site | Kumamoto | — | Japan | — |
| Novo Nordisk Investigational Site | Kurashiki-shi, Okayama | — | Japan | — |
| Novo Nordisk Investigational Site | Kyoto-shi, Kyoto | — | Japan | — |
| Novo Nordisk Investigational Site | Mitaka-shi, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Mito-shi, Ibaraki | — | Japan | — |
| Novo Nordisk Investigational Site | Miyazaki | — | Japan | — |
| Novo Nordisk Investigational Site | Osaka | — | Japan | — |
| Novo Nordisk Investigational Site | Ota-ku, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Sapporo | — | Japan | — |
| Novo Nordisk Investigational Site | Sapporo-shi, Hokkaido | — | Japan | — |
| Novo Nordisk Investigational Site | Sendai-shi, Miyagi | — | Japan | — |
| Novo Nordisk Investigational Site | Shimotsuke-shi, Tochigi | — | Japan | — |
| Novo Nordisk Investigational Site | Shinagawa-ku, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Shizuoka-shi, Shizuoka | — | Japan | — |
| Novo Nordisk Investigational Site | Suita-shi, Osaka | — | Japan | — |
| Novo Nordisk Investigational Site | Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Toshima-ku, Tokyo | — | Japan | — |
| Novo Nordisk Investigational Site | Yamato-shi, Kanagawa | — | Japan | — |
Oversight & Regulatory
Data Monitoring Committee: No
FDA Regulation
- FDA Regulated Drug: No
- FDA Regulated Device: No
Results
Participant Flow
Study Groups: 4
- FG000: Oral Semaglutide 3 mg
- FG001: Oral Semaglutide 7 mg
- FG002: Oral Semaglutide 14 mg
- FG003: Dulaglutide 0.75 mg
Overall Study
| Milestone | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|
| STARTED | 131 | 132 | 130 | 65 |
| Full Analysis Set (FAS) | 131 | 132 | 130 | 65 |
| Safety Analysis Set (SAS) | 131 | 132 | 130 | 65 |
| COMPLETED | 128 | 130 | 127 | 63 |
| NOT COMPLETED | 3 | 2 | 3 | 2 |
Withdrawals
Withdrawal by Subject
Oral Semaglutide 3 mg: 3
Oral Semaglutide 7 mg: 2
Oral Semaglutide 14 mg: 2
Dulaglutide 0.75 mg: 2 Lost to Follow-up
Oral Semaglutide 3 mg: 0
Oral Semaglutide 7 mg: 0
Oral Semaglutide 14 mg: 1
Dulaglutide 0.75 mg: 0
Baseline Characteristics
Age, Continuous
| Characteristic | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg | Total |
|---|---|---|---|---|---|
| — | 59 (10) | 58 (11) | 57 (10) | 61 (9) | 58 (10) |
Sex: Female, Male
| Characteristic | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg | Total |
|---|---|---|---|---|---|
| Female | 31 | 42 | 30 | 14 | 117 |
| Male | 100 | 90 | 100 | 51 | 341 |
Ethnicity (NIH/OMB)
| Characteristic | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 131 | 132 | 130 | 65 | 458 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
Race (NIH/OMB)
| Characteristic | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 131 | 132 | 130 | 65 | 458 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
Outcome Measures
Primary Outcomes (1)
Number of Treatment-emergent Adverse Events (TEAEs)
Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame: Weeks 0-57 | Units: Events | Type: NUMBER
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Value | 330 | 350 | 324 | 178 |
Secondary Outcomes (32)
Change in HbA1c
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Percentage of HbA1c | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -1.1 (0.9) | -1.7 (0.9) | -2.0 (1.0) | -1.6 (0.9) |
| Week 52 | -0.8 (1.0) | -1.4 (1.0) | -1.8 (1.0) | -1.4 (0.9) |
Change in Fasting Plasma Glucose
Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: mmol/L | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -1.23 (1.54) | -2.25 (1.93) | -2.72 (1.86) | -2.22 (1.71) |
| Week 52 | -0.95 (1.72) | -1.96 (1.72) | -2.18 (2.50) | -1.80 (1.71) |
Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile
Change from baseline (week 0) in mean 7-point SMPG profile was evaluated at weeks 26 and 52. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: mmol/L | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -1.8 (2.2) | -2.7 (2.1) | -3.5 (2.3) | -2.9 (2.4) |
| Week 52 | -1.7 (2.1) | -2.5 (2.4) | -3.3 (2.6) | -2.6 (2.6) |
Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All Meals
Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: mmol/L | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -0.9 (2.5) | -1.3 (2.0) | -1.2 (2.4) | -0.7 (2.3) |
| Week 52 | -0.6 (2.6) | -0.8 (2.0) | -0.9 (2.6) | -0.7 (2.3) |
Change in Body Weight (kg)
Change from baseline (week 0) in body weight was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: kg | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -0.1 (2.0) | -1.0 (3.0) | -2.2 (3.2) | 0.3 (2.1) |
| Week 52 | 0.0 (2.4) | -0.9 (3.4) | -1.7 (3.5) | 1.0 (2.7) |
Change in Body Weight (%)
Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Percentage change | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -0.28 (2.79) | -1.49 (4.25) | -3.21 (4.32) | 0.25 (3.33) |
| Week 52 | -0.02 (3.28) | -1.34 (4.77) | -2.33 (4.67) | 1.25 (4.06) |
Change in Body Mass Index (BMI)
Change from baseline (week 0) in BMI was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Kilogram per square meter (kg/m^2) | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | -0.1 (0.7) | -0.4 (1.1) | -0.8 (1.2) | 0.1 (0.8) |
| Week 52 | -0.0 (0.9) | -0.3 (1.3) | -0.6 (1.3) | 0.3 (1.0) |
Change in Waist Circumference
Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Centimeters (cm) | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 0.0 (3.1) | -0.6 (3.4) | -1.2 (4.3) | 0.3 (2.9) |
| Week 52 | -0.1 (3.6) | -0.8 (3.9) | -1.7 (4.2) | 0.7 (3.6) |
Change in Fasting Total Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting total cholesterol (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of fasting total cholesterol | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 0.96 (9.4) | 0.91 (12.3) | 0.91 (12.3) | 0.92 (8.8) |
| Week 52 | 0.98 (12.7) | 0.95 (13.3) | 0.94 (12.5) | 0.93 (11.4) |
Change in Fasting Low-density Lipoprotein (LDL) - Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting low-density lipoprotein (LDL) (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of fasting LDL | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 0.92 (15.9) | 0.88 (18.4) | 0.87 (20.7) | 0.88 (14.5) |
| Week 52 | 0.98 (17.4) | 0.94 (19.0) | 0.92 (18.6) | 0.91 (16.2) |
Change in Fasting High-density Lipoprotein (HDL) - Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting high-density lipoprotein (HDL) (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of fasting HDL | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 1.02 (13.1) | 0.99 (12.8) | 1.00 (12.5) | 0.99 (11.6) |
| Week 52 | 1.03 (11.2) | 0.99 (14.5) | 1.01 (13.1) | 1.00 (11.6) |
Change in Fasting Very-low Density Lipoprotein (VLDL) - Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting very-low density lipoprotein (VLDL) (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of fasting VLDL | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 1.03 (37.9) | 0.92 (32.3) | 0.96 (33.6) | 0.93 (33.5) |
| Week 52 | 0.90 (33.3) | 0.87 (39.4) | 0.86 (36.9) | 0.88 (31.6) |
Change in Fasting Triglyceride (Ratio to Baseline)
Change from baseline (week 0) in fasting triglycerides (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of fasting triglycerides | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 1.03 (41.1) | 0.91 (34.1) | 0.96 (34.0) | 0.93 (33.7) |
| Week 52 | 0.89 (33.9) | 0.87 (43.0) | 0.87 (38.3) | 0.88 (30.8) |
Participants Who Achieve HbA1c Below 7% (53 mmol/Mol), American Diabetes Association Target (Yes/No)
Participants who achieved HbA1c below 7.0% (53 millimoles per mole [mmol/mol]) according to American Diabetes Association (ADA) target (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | — | — | — | — |
| Yes | 59 | 96 | 105 | 45 |
| No | 69 | 32 | 23 | 19 |
| Week 52 | — | — | — | — |
| Yes | 43 | 77 | 90 | 32 |
| No | 83 | 52 | 37 | 31 |
Participants Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target (Yes/No)
Participants who achieved HbA1c below or equal to 6.5% (48 mmol/mol), American Association of Clinical Endocrinologists (AACE) target (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | — | — | — | — |
| Yes | 40 | 67 | 88 | 31 |
| No | 88 | 61 | 40 | 33 |
| Week 52 | — | — | — | — |
| Yes | 22 | 50 | 69 | 23 |
| No | 104 | 79 | 58 | 40 |
Participants Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/No)
Participants who achieved HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia episodes and without weight gain (yes/no) at weeks 26 and 52 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | — | — | — | — |
| Yes | 39 | 63 | 84 | 25 |
| No | 89 | 65 | 44 | 39 |
| Week 52 | — | — | — | — |
| Yes | 23 | 53 | 71 | 16 |
| No | 103 | 76 | 56 | 47 |
Participants Who Achieve HbA1c Reduction More Than or Equal to 1% (10.9 mmol/Mol) and Weight Loss More Than or Equal to 3% (Yes/No)
Participants who achieved HbA1c reduction more than or equal to 1% (10.9 mmol/mol) and weight loss more than or equal to 3% (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | — | — | — | — |
| Yes | 15 | 34 | 62 | 8 |
| No | 113 | 94 | 66 | 56 |
| Week 52 | — | — | — | — |
| Yes | 11 | 32 | 42 | 7 |
| No | 115 | 97 | 85 | 56 |
Participants Who Achieve Weight Loss More Than or Equal to 5% (Yes/No).
Participants who achieved weight loss more than or equal to 5% (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | — | — | — | — |
| Yes | 6 | 23 | 39 | 4 |
| No | 122 | 105 | 89 | 60 |
| Week 52 | — | — | — | — |
| Yes | 7 | 21 | 28 | 4 |
| No | 120 | 108 | 99 | 59 |
Participants Who Achieve Weight Loss More Than or Equal to 10% (Yes/No)
Participants who achieved weight loss more than or equal to 10% (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | — | — | — | — |
| Yes | 0 | 6 | 8 | 1 |
| No | 128 | 122 | 120 | 63 |
| Week 52 | — | — | — | — |
| Yes | 0 | 9 | 7 | 0 |
| No | 127 | 120 | 120 | 63 |
Time to Additional Anti-diabetic Medication
Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Weeks 0-52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 0 to week 26 | 1 | 3 | 6 | 1 |
| Week 0 to week 52 | 24 | 13 | 8 | 8 |
Statistical Analyses
- Method: Regression, Cox | P-value: 0.2963
- Method: Regression, Cox | P-value: 0.5997
- Method: Regression, Cox | P-value: 0.1871
Time to Rescue Medication
Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame: Weeks 0-52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 0 to week 26 | 0 | 0 | 1 | 1 |
| Week 0 to week 52 | 22 | 8 | 2 | 6 |
Statistical Analyses
- Method: Regression, Cox | P-value: 0.1672
- Method: Regression, Cox | P-value: 0.3391
- Method: Regression, Cox | P-value: 0.0110
Change in Amylase (Ratio to Baseline)
Change from baseline (week 0) in amylase (measured as units per liter [U/L]) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of amylase | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 1.01 (15.1) | 1.07 (18.1) | 1.10 (19.4) | 1.05 (23.4) |
| Week 52 | 1.03 (18.5) | 1.10 (23.8) | 1.11 (20.0) | 1.07 (18.8) |
Change in Lipase (Ratio to Baseline)
Change from baseline (week 0) in lipase (measured as U/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame: Week 0, week 26, week 52 | Units: Ratio of lipase | Type: GEOMETRIC_MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 1.15 (37.4) | 1.27 (35.8) | 1.40 (42.8) | 1.14 (48.3) |
| Week 52 | 1.11 (34.7) | 1.36 (50.3) | 1.40 (42.0) | 1.15 (57.7) |
Change in Pulse Rate
Change from baseline (week 0) in pulse rate was evaluated at weeks 26 and 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame: Week 0, week 26, week 52 | Units: Beats per minute (beats/min) | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26 | 3 (9) | 4 (10) | 4 (9) | 4 (9) |
| Week 52 | 3 (10) | 3 (9) | 3 (9) | 2 (10) |
Change in Blood Pressure
Change from baseline (week 0) in blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]) was evaluated at weeks 26 and 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame: Week 0, week 26, week 52 | Units: Millimeters of mercury (mmHg) | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Week 26: SBP | -3.0 (13.0) | -5.0 (13.0) | -6.0 (15.0) | -4.0 (12.0) |
| Week 52: SBP | -2.0 (14.0) | -2.0 (13.0) | -2.0 (13.0) | -3.0 (13.0) |
| Week 26: DBP | -1.0 (9.0) | -1.0 (9.0) | -2.0 (10.0) | -1.0 (11.0) |
| Week 52: DBP | 0.0 (9.0) | 0.0 (9.0) | -1.0 (10.0) | 0.0 (9.0) |
Change in ECG Evaluation
Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26 and 52. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS) and abnormal and clinically significant (CS)) from week 0 to week 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week 0, week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Normal (week 0) to normal (week 26) | 103 | 110 | 99 | 54 |
| Normal (week 0) to abnormal NCS (week 26) | 4 | 3 | 3 | 4 |
| Normal (week 0) to abnormal CS (week 26) | 2 | 0 | 0 | 0 |
| Abnormal NCS (week 0) to normal (week 26) | 0 | 3 | 4 | 2 |
| Abnormal NCS (week 0) to abnormal NCS (week 26) | 16 | 12 | 18 | 4 |
| Abnormal NCS (week 0) to abnormal CS (week 26) | 0 | 0 | 2 | 0 |
| Abnormal CS (week 0) to normal (week 26) | 1 | 0 | 0 | 0 |
| Abnormal CS (week 0) to abnormal NCS (week 26) | 0 | 0 | 0 | 0 |
| Abnormal CS (week 0) to abnormal CS (week 26) | 2 | 1 | 2 | 0 |
| Normal (week 0) to normal (week 52) | 103 | 108 | 95 | 55 |
| Normal (week 0) to abnormal NCS (week 52) | 3 | 5 | 6 | 2 |
| Normal (week 0) to abnormal CS (week 52) | 2 | 0 | 1 | 0 |
| Abnormal (week 0) NCS to normal (week 52) | 2 | 5 | 6 | 3 |
| Abnormal (week 0) NCS to abnormal NCS (week 52) | 13 | 10 | 18 | 3 |
| Abnormal (week 0) NCS to abnormal CS (week 52) | 0 | 0 | 0 | 0 |
| Abnormal (week 0) CS to normal (week 52) | 1 | 1 | 0 | 0 |
| Abnormal (week 0) CS to abnormal NCS (week 52) | 0 | 0 | 0 | 0 |
| Abnormal (week 0) CS to abnormal CS (week 52) | 3 | 0 | 1 | 0 |
Change in Physical Examination
Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2), week 26 and weeks 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.
Time Frame: Week -2, week 26, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| 1) Cardiovascular system (week -2) | — | — | — | — |
| Normal | 128 | 132 | 128 | 60 |
| Abnormal NCS | 1 | 0 | 0 | 1 |
| Abnormal CS | 2 | 0 | 2 | 4 |
| 1) Cardiovascular system (week 26) | — | — | — | — |
| Normal | 125 | 128 | 125 | 59 |
| Abnormal NCS | 0 | 0 | 1 | 1 |
| Abnormal CS | 3 | 0 | 2 | 4 |
| 1) Cardiovascular system (week 52) | — | — | — | — |
| Normal | 124 | 129 | 126 | 58 |
| Abnormal NCS | 1 | 0 | 0 | 1 |
| Abnormal CS | 2 | 0 | 1 | 4 |
| 2) Central and peripheral nervous system (week -2) | — | — | — | — |
| Normal | 131 | 131 | 130 | 64 |
| Abnormal NCS | 0 | 1 | 0 | 0 |
| Abnormal CS | 0 | 0 | 0 | 1 |
| 2) Central and peripheral nervous system (week 26) | — | — | — | — |
| Normal | 128 | 127 | 128 | 62 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 1 | 0 | 2 |
| 2) Central and peripheral nervous system (week 56) | — | — | — | — |
| Normal | 127 | 128 | 126 | 62 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 1 | 1 | 1 |
| 3) Gastrointestinal system, incl. mouth (week -2) | — | — | — | — |
| Normal | 126 | 128 | 129 | 60 |
| Abnormal NCS | 0 | 2 | 0 | 0 |
| Abnormal CS | 5 | 2 | 1 | 5 |
| 3) Gastrointestinal system, incl. mouth (week 26) | — | — | — | — |
| Normal | 122 | 123 | 125 | 60 |
| Abnormal NCS | 0 | 2 | 1 | 0 |
| Abnormal CS | 6 | 3 | 2 | 4 |
| 3) Gastrointestinal system, incl. mouth (week 52) | — | — | — | — |
| Normal | 122 | 124 | 126 | 59 |
| Abnormal NCS | 1 | 3 | 1 | 0 |
| Abnormal CS | 4 | 2 | 0 | 4 |
| 4.General appearance (week -2) | — | — | — | — |
| Normal | 131 | 132 | 130 | 64 |
| Abnormal NCS | 0 | 0 | 0 | 1 |
| Abnormal CS | 0 | 0 | 0 | 0 |
| 4.General appearance (week 26) | — | — | — | — |
| Normal | 127 | 128 | 127 | 62 |
| Abnormal NCS | 1 | 0 | 1 | 1 |
| Abnormal CS | 0 | 0 | 0 | 1 |
| 4.General appearance (week 52) | — | — | — | — |
| Normal | 126 | 128 | 127 | 62 |
| Abnormal NCS | 0 | 0 | 0 | 1 |
| Abnormal CS | 1 | 1 | 0 | 0 |
| 5.Head, ears, eyes, nose, throat, neck (week -2) | — | — | — | — |
| Normal | 121 | 127 | 124 | 55 |
| Abnormal NCS | 3 | 2 | 2 | 4 |
| Abnormal CS | 7 | 3 | 4 | 6 |
| 5.Head, ears, eyes, nose, throat, neck (week 26) | — | — | — | — |
| Normal | 119 | 122 | 125 | 56 |
| Abnormal NCS | 4 | 1 | 1 | 3 |
| Abnormal CS | 5 | 5 | 2 | 5 |
| 5.Head, ears, eyes, nose, throat, neck (week 52) | — | — | — | — |
| Normal | 117 | 123 | 122 | 53 |
| Abnormal NCS | 3 | 1 | 2 | 4 |
| Abnormal CS | 7 | 5 | 3 | 6 |
| 6. Lymph node palpation (week -2) | — | — | — | — |
| Normal | 131 | 131 | 129 | 65 |
| Abnormal NCS | 0 | 1 | 1 | 0 |
| Abnormal CS | 0 | 0 | 0 | 0 |
| 6. Lymph node palpation (week 26) | — | — | — | — |
| Normal | 128 | 127 | 128 | 64 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 1 | 0 | 0 |
| 6. Lymph node palpation (week 52) | — | — | — | — |
| Normal | 127 | 128 | 127 | 63 |
| Abnormal NCS | 0 | 1 | 0 | 0 |
| Abnormal CS | 0 | 0 | 0 | 0 |
| 7. Musculoskeletal system (week -2) | — | — | — | — |
| Normal | 128 | 126 | 127 | 64 |
| Abnormal NCS | 1 | 3 | 2 | 0 |
| Abnormal CS | 2 | 3 | 1 | 1 |
| 7. Musculoskeletal system (week 26) | — | — | — | — |
| Normal | 123 | 123 | 124 | 61 |
| Abnormal NCS | 2 | 2 | 2 | 0 |
| Abnormal CS | 3 | 3 | 2 | 3 |
| 7. Musculoskeletal system (week 52) | — | — | — | — |
| Normal | 120 | 125 | 123 | 62 |
| Abnormal NCS | 4 | 1 | 2 | 0 |
| Abnormal CS | 3 | 3 | 2 | 1 |
| 8) Respiratory system (week -2) | — | — | — | — |
| Normal | 131 | 132 | 130 | 64 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 0 | 0 | 1 |
| 8) Respiratory system (week 26) | — | — | — | — |
| Normal | 128 | 127 | 128 | 62 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 1 | 0 | 2 |
| 8) Respiratory system (week 52) | — | — | — | — |
| Normal | 126 | 127 | 127 | 62 |
| Abnormal NCS | 0 | 1 | 0 | 0 |
| Abnormal CS | 1 | 1 | 0 | 1 |
| 9) Skin (week -2) | — | — | — | — |
| Normal | 125 | 127 | 128 | 63 |
| Abnormal NCS | 3 | 0 | 1 | 0 |
| Abnormal CS | 3 | 5 | 1 | 2 |
| 9) Skin (week 26) | — | — | — | — |
| Normal | 124 | 127 | 126 | 62 |
| Abnormal NCS | 1 | 0 | 1 | 1 |
| Abnormal CS | 3 | 1 | 1 | 1 |
| 9) Skin (week 52) | — | — | — | — |
| Normal | 123 | 127 | 125 | 61 |
| Abnormal NCS | 1 | 1 | 1 | 0 |
| Abnormal CS | 3 | 1 | 1 | 2 |
| 10) Thyroid gland (week -2) | — | — | — | — |
| Normal | 130 | 130 | 129 | 64 |
| Abnormal NCS | 0 | 2 | 0 | 0 |
| Abnormal CS | 1 | 0 | 1 | 1 |
| 10) Thyroid gland (week 26) | — | — | — | — |
| Normal | 128 | 128 | 128 | 63 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 0 | 0 | 1 |
| 10) Thyroid gland (week 52) | — | — | — | — |
| Normal | 127 | 129 | 127 | 62 |
| Abnormal NCS | 0 | 0 | 0 | 0 |
| Abnormal CS | 0 | 0 | 0 | 1 |
Change in Eye Examination Category
Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame: Week -2, week 52 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Left eye (week -2) | — | — | — | — |
| Normal | 96 | 97 | 90 | 48 |
| Abnormal NCS | 7 | 2 | 2 | 4 |
| Abnormal CS | 28 | 33 | 38 | 13 |
| Left eye (week 52) | — | — | — | — |
| Normal | 90 | 92 | 93 | 46 |
| Abnormal NCS | 10 | 8 | 3 | 3 |
| Abnormal CS | 26 | 29 | 31 | 14 |
| Right eye (week -2) | — | — | — | — |
| Normal | 94 | 98 | 89 | 44 |
| Abnormal NCS | 6 | 3 | 2 | 6 |
| Abnormal CS | 31 | 31 | 39 | 15 |
| Right eye (week 52) | — | — | — | — |
| Normal | 93 | 90 | 90 | 48 |
| Abnormal NCS | 9 | 8 | 6 | 4 |
| Abnormal CS | 24 | 31 | 31 | 11 |
Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame: Weeks 0-57 | Units: Episodes | Type: NUMBER
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Value | 4 | 4 | 4 | 0 |
Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Participants with treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame: Weeks 0-57 | Units: Participants | Type: COUNT_OF_PARTICIPANTS
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| Value | 3 | 3 | 4 | 0 |
Change in SF-36v2 (Acute Version) Health Survey Scores: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)
SF-36 is a 36-item patient-reported survey of patient health that measures the participant’s overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.
Time Frame: Week 0, week 26, week 52 | Units: Score on a scale | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| 1) Physical functioning (week 26) | -0.18 (3.34) | 0.08 (4.04) | -0.06 (4.16) | -0.24 (3.71) |
| 1) Physical functioning (week 52) | -0.37 (3.34) | 0.70 (4.08) | -0.02 (4.27) | -0.61 (5.01) |
| 2) Role Physical (week 26) | -0.58 (5.12) | 0.59 (5.49) | -1.01 (6.00) | -0.48 (5.22) |
| 2) Role Physical (week 52) | -0.92 (5.66) | 0.05 (6.13) | -0.92 (7.26) | -0.28 (5.31) |
| 3) Bodily Pain (week 26) | -0.88 (8.39) | 0.05 (8.26) | -0.99 (9.32) | -0.44 (7.25) |
| 3) Bodily Pain (week 52) | -2.72 (9.74) | -0.27 (8.88) | 0.01 (9.48) | 0.24 (5.77) |
| 4)General Health (week 26) | 0.42 (4.59) | 0.09 (5.26) | 0.71 (5.94) | -1.03 (5.28) |
| 4)General Health (week 52) | -0.34 (5.27) | 0.01 (5.27) | 0.59 (6.13) | -0.97 (6.63) |
| 5) Vitality (week 26) | -1.62 (7.49) | -0.79 (7.08) | -0.83 (6.84) | -1.40 (7.94) |
| 5) Vitality (week 52) | -0.90 (7.29) | -0.11 (7.03) | 0.09 (6.83) | -0.86 (7.63) |
| 6) Social functioning (week 26) | -0.77 (5.87) | -0.15 (5.95) | -0.15 (6.08) | 0.15 (4.98) |
| 6) Social functioning (week 52) | -1.98 (8.10) | -0.42 (6.80) | -0.12 (5.92) | -0.08 (6.73) |
| 7) Role emotional (week 26) | -0.54 (7.87) | 0.42 (6.96) | -1.16 (6.60) | -1.01 (6.28) |
| 7) Role emotional (week 52) | -1.02 (7.70) | 0.59 (6.89) | -1.05 (8.16) | -1.21 (7.31) |
| 8) Mental health (week 26) | -1.03 (6.54) | 0.16 (6.66) | -0.41 (7.32) | 0.27 (7.34) |
| 8) Mental health (week 52) | -1.64 (7.63) | -0.35 (6.68) | 0.27 (7.58) | -0.31 (10.24) |
| Physical component summary (week 26) | -0.17 (4.19) | 0.14 (4.27) | -0.23 (5.24) | -0.57 (4.80) |
| Physical component summary (week 52) | -0.88 (4.73) | 0.19 (4.91) | -0.03 (5.34) | -0.24 (4.52) |
| Mental component summary (week 26) | -1.13 (6.54) | -0.07 (5.85) | -0.71 (5.91) | -0.42 (6.04) |
| Mental component summary (week 52) | -1.52 (7.26) | -0.19 (6.31) | -0.23 (6.15) | -0.74 (8.57) |
Diabetes Therapy-Related Quality of Life (DTR-QoL): Total Score and Scores for the 4 Domains
DTR-QoL questionnaire is a 29-item patient-reported survey of patient health that measures the influence of diabetes treatment on health related-QoL on 4 domains on individual scale ranges: “Burden on social activities and daily activities”, “Anxiety and dissatisfaction with treatment”, “Hypoglycemia” and “Satisfaction with treatment” on a 7-point graded response scale. The domain score is calculated from the mean score of the attribute items, and the scoring range is converted to 0 - 100 (best-case response = 100; worst case response = 0). The total score, after simple addition of the item scores, is converted to 0 - 100 (best-case response = 100; worst case response = 0). Change from baseline (week 0) in the scores were evaluated at week 26, week 52. Data based on in-trial observation period is presented. W26 and W52 refer to week 26 and week 52 respectively.
Time Frame: week 0, week 26, week 52 | Units: Score on a scale | Type: MEAN
| Measurement | Oral Semaglutide 3 mg | Oral Semaglutide 7 mg | Oral Semaglutide 14 mg | Dulaglutide 0.75 mg |
|---|---|---|---|---|
| 1.Burden on social and daily activities (W26) | 6.44 (17.59) | 6.93 (18.09) | 4.88 (16.46) | 5.29 (19.65) |
| 1.Burden on social and daily activities (W52) | 4.73 (18.69) | 6.81 (18.85) | 5.44 (16.57) | 3.99 (19.25) |
| 2.Anxiety and dissatisfaction with treatment(W26) | 6.54 (18.08) | 10.94 (17.83) | 12.24 (17.41) | 9.24 (20.87) |
| 2.Anxiety and dissatisfaction with treatment(W52) | 0.98 (18.60) | 9.93 (19.61) | 11.37 (18.68) | 3.14 (19.79) |
| 3.Hypoglycemia (W26) | 5.18 (20.62) | 1.95 (18.14) | 2.67 (21.14) | 3.26 (19.82) |
| 3.Hypoglycemia (W52) | 4.20 (19.61) | 1.94 (19.36) | 3.87 (20.70) | -0.66 (23.10) |
| 4.Satisfaction with treatment(W26) | 9.67 (19.08) | 10.81 (24.53) | 14.29 (28.11) | 13.15 (24.69) |
| 4.Satisfaction with treatment(W52) | 2.46 (19.66) | 7.88 (23.92) | 15.49 (27.01) | 6.35 (26.22) |
| Total score(W26) | 6.74 (13.01) | 7.88 (14.40) | 7.90 (12.72) | 7.18 (15.56) |
| Total score(W52) | 3.31 (13.47) | 7.15 (15.69) | 8.25 (12.81) | 3.44 (14.89) |
Adverse Events
Reporting Threshold: 5
Time Frame: Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product.
Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Event Summary
| Group | Deaths | Serious Events | Other Events |
|---|---|---|---|
| Oral Semaglutide 3 mg | 0/131 (0.0%) | 9/131 (6.9%) | 65/131 (49.6%) |
| Oral Semaglutide 7 mg | 0/132 (0.0%) | 4/132 (3.0%) | 79/132 (59.8%) |
| Oral Semaglutide 14 mg | 0/130 (0.0%) | 7/130 (5.4%) | 84/130 (64.6%) |
| Dulaglutide 0.75 mg | 0/65 (0.0%) | 1/65 (1.5%) | 36/65 (55.4%) |
| Total | 0/458 (0.0%) | 21/458 (4.6%) | 264/458 (57.6%) |
Serious Adverse Events (24)
| Event | Oral Semaglutide 3 mg (n=131) | Oral Semaglutide 7 mg (n=132) | Oral Semaglutide 14 mg (n=130) | Dulaglutide 0.75 mg (n=65) |
|---|---|---|---|---|
| Acute myocardial infarction | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Angina pectoris | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 1 (1.5%) |
| Appendicitis | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Atrioventricular block second degree | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (1.5%) |
| Cardiac ablation | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Cellulitis | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Colorectal cancer | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) |
| Diabetic retinopathy | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Femoral neck fracture | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) |
| Gastrointestinal inflammation | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Herpes zoster | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Ischaemic cerebral infarction | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Large intestine polyp | 1 (0.8%) | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) |
| Osteomyelitis | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Peritonitis | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Pneumonia | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) |
| Prostate cancer | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Rotator cuff syndrome | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Shock | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) |
| Sudden hearing loss | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Benign prostatic hyperplasia | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Colon adenoma | 0 (0.0%) | 0 (0.0%) | 1 (0.8%) | 0 (0.0%) |
| Rectal adenocarcinoma | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Spinal operation | 1 (0.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Total events | 11 | 5 | 8 | 2 |
Other Adverse Events (12)
| Event | Oral Semaglutide 3 mg (n=131) | Oral Semaglutide 7 mg (n=132) | Oral Semaglutide 14 mg (n=130) | Dulaglutide 0.75 mg (n=65) |
|---|---|---|---|---|
| Abdominal discomfort | 3 (2.3%) | 6 (4.5%) | 9 (6.9%) | 1 (1.5%) |
| Back pain | 4 (3.1%) | 5 (3.8%) | 3 (2.3%) | 4 (6.2%) |
| Constipation | 12 (9.2%) | 16 (12.1%) | 20 (15.4%) | 6 (9.2%) |
| Decreased appetite | 0 (0.0%) | 12 (9.1%) | 6 (4.6%) | 3 (4.6%) |
| Diabetic retinopathy | 6 (4.6%) | 12 (9.1%) | 5 (3.8%) | 2 (3.1%) |
| Diarrhoea | 2 (1.5%) | 2 (1.5%) | 10 (7.7%) | 4 (6.2%) |
| Gastrooesophageal reflux disease | 5 (3.8%) | 2 (1.5%) | 8 (6.2%) | 0 (0.0%) |
| Influenza | 9 (6.9%) | 9 (6.8%) | 5 (3.8%) | 2 (3.1%) |
| Nasopharyngitis | 34 (26.0%) | 39 (29.5%) | 39 (30.0%) | 19 (29.2%) |
| Nausea | 7 (5.3%) | 11 (8.3%) | 12 (9.2%) | 6 (9.2%) |
| Upper respiratory tract inflammation | 4 (3.1%) | 4 (3.0%) | 3 (2.3%) | 5 (7.7%) |
| Vomiting | 3 (2.3%) | 1 (0.8%) | 9 (6.9%) | 1 (1.5%) |
Additional Information
PI is Sponsor Employee: No
Point of Contact
- Title: Clinical Reporting Anchor and Disclosure (1452)
- Organization: Novo Nordisk A/S
- Email: clinicaltrials@novonordisk.com
- Phone: (+1) 866-867-7178
IPD Sharing Statement
IPD Sharing: YES
According to the Novo Nordisk disclosure commitent on novonordisk-trials.com
URL: http://novonordisk-trials.com/
Documents & Links
Study Documents
| Document Type | Date | Size | Filename |
|---|---|---|---|
| Protocol, Prot | 2019-01-15 | 1,212,817 bytes | Prot_000.pdf |
| SAP, SAP | 2018-11-02 | 508,998 bytes | SAP_001.pdf |
References (5)
- [1] Ishii H, Hansen BB, Langer J, Horio H. Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial. Diabetes Ther. 2021 Feb;12(2):613-623. doi: 10.1007/s13300-020-00985-w. Epub 2021 Jan 18. (PMID: 33460016) [RESULT]
- [2] Yabe D, Nakamura J, Kaneto H, Deenadayalan S, Navarria A, Gislum M, Inagaki N; PIONEER 10 Investigators. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020 May;8(5):392-406. doi: 10.1016/S2213-8587(20)30074-7. (PMID: 32333876) [RESULT]
- [3] Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4. (PMID: 32998732) [DERIVED]
- [4] Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13. (PMID: 32267058) [DERIVED]
- [5] Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5. (PMID: 31903692) [DERIVED]
Paper sources
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Abstract screening results
Extraction pilot
Extraction results
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