Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted globally. The aim of the trial is to examine the dose range, escalation and efficacy of oral semaglutide in subjects with type 2 diabetes.
Interventions
DRUGsemaglutide
Once-daily oral administration as tablets.
DRUGoral placebo
Once-daily oral administration as tablets.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* BMI above or equal to 25 and below or equal to 40 kg/m\^2 * Subjects diagnosed with T2D (Type 2 diabetes) treated with diet and exercise and/or who have been on a stable dose of metformin for at least 30 days prior to screening * HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive)
Exclusion criteria
* Subjects on selected oral medication with a narrow therapeutic window, such as warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline and anticonvulsants * History of chronic pancreatitis or idiopathic acute pancreatitis * Chronic malabsorption, regardless of aetiology * History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease * Treatment with glucose lowering agent(s) other than metformin as stated in the inclusion criteria in a period of 90 days before the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (Glycosylated Haemoglobin) | Week 0, week 26 | Change from baseline (week 0) in HbA1c was evaluated at week 26. The endpoint was evaluated 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Week 0, Week 26 | Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated 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. |
| Change in Waist Circumference | Week 0, week 26 | Change from baseline (week 0) in waist circumference was evaluated at week 26. The endpoint was evaluated 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. |
| Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | After 26 weeks of treatment | Participants who achieved HbA1c \<7.0%, was evaluated at week 26. The endpoint was evaluated 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. |
| Number of Treatment Emergent Adverse Events (TEAEs) Recorded | Weeks 0-31 | TEAEs were recorded during weeks 0-31 (26 weeks treatment period+5 weeks 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. |
| Number of Confirmed Hypoglycaemic Episodes Recorded | Weeks 0-31 | Treatment-emergent confirmed hypoglycaemic episodes were recorded during weeks 0-31 (26 weeks treatment period + 5 weeks 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. Confirmed hypoglycaemic episode is an episode that is severe according to the American Diabetes Association (ADA) classification or plasma glucose value \<3.1 mmol/L with or without symptoms consistent with hypoglycaemia. |
| Change in Body Mass Index (BMI) | Week 0, week 26 | Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. The endpoint was evaluated 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. |
Countries
Austria, Bulgaria, Canada, Denmark, Germany, Israel, Italy, Malaysia, Serbia, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 100 sites in 14 countries as follows: Austria (6), Bulgaria (3), Canada (6), Denmark (6), Germany (6), Israel (6), Italy (4), Malaysia (4), Serbia (1), South Africa (3), Spain (5), Sweden (3), United Kingdom (8) and United States (39).
Pre-assignment details
Data presented in participant flow is based on 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.
Participants by arm
| Arm | Count |
|---|---|
| Oral Semaglutide 2.5 mg Participants were to take 2.5 mg oral semaglutide tablets once daily for 26 weeks. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets. | 70 |
| Oral Semaglutide 5 mg Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 2.5 mg from week 1 to 4 and 5 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets. | 70 |
| Oral Semaglutide 10 mg Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4 and 10 mg from week 5 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets. | 69 |
| Oral Semaglutide 20 mg Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8 and 20 mg from week 9 to 26.
Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets. | 70 |
| Oral Semaglutide 40 mg Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 4, 10 mg from week 5 to 8, 20 mg from week 9 to 12 and 40 mg from week 13 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets. | 71 |
| Oral Semaglutide 40 mg Slow Dose-escalation Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 8, 10 mg from week 9 to 16, 20 mg from week 17 to 24 and 40 mg from week 25 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets. | 70 |
| Oral Semaglutide 40 mg Fast Dose-escalation Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 26: 5 mg from week 1 to 2, 10 mg from week 3 to 4, 20 mg from week 5 to 6 and 40 mg from week 7 to 26. Semaglutide tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than semaglutide tablets could be taken upto 2 hours prior to administration of semaglutide tablets. The semaglutide tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide tablets. Oral medication other than semaglutide tablets could only be taken 2 hours after administration of semaglutide tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide tablets | 70 |
| Subcutaneous Semaglutide 1 mg Participants were to administer subcutaneous semaglutide injections once weekly in a dose escalation manner from week 1 to 26: 0.25 mg from week 1 to 4, 0.50 mg from week 5 to 8 and 1.0 mg from week 9 to 26. Semaglutide injections were to be administered in the thigh, abdomen or upper arm, at any time of day (same day of the week) irrespective of meals. | 69 |
| Placebo Participants were to take oral semaglutide placebo tablets once daily from week 1 to 26. Semaglutide placebo tablets were to be taken once daily in the morning in a fasting state (atleast for 6 hours). Water and oral medication other than the semaglutide placebo tablets could be taken upto 2 hours prior to administration of semaglutide placebo tablets. The semaglutide placebo tablets could be taken with up to 120 mL of water. Participants were not allowed to take food and water for at least 30 minutes after administration of semaglutide placebo tablets. Oral medication other than semaglutide placebo tablets could only be taken 2 hours after administration of semaglutide placebo tablets. If taken along with food, oral medication could be administered 30 minutes after administration of semaglutide placebo tablets. | 71 |
| Total | 630 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 3 | 2 | 1 | 2 | 1 | 3 | 3 | 1 |
| Overall Study | Other | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 2 | 0 | 2 | 2 | 1 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 4 | 2 | 4 | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Subcutaneous Semaglutide 1 mg | Oral Semaglutide 40 mg Fast Dose-escalation | Oral Semaglutide 40 mg Slow Dose-escalation | Oral Semaglutide 40 mg | Oral Semaglutide 20 mg | Oral Semaglutide 10 mg | Oral Semaglutide 5 mg | Oral Semaglutide 2.5 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.1 Years STANDARD_DEVIATION 10.6 | 58.9 Years STANDARD_DEVIATION 10.3 | 56.8 Years STANDARD_DEVIATION 11.8 | 57.7 Years STANDARD_DEVIATION 10.8 | 57.1 Years STANDARD_DEVIATION 10.5 | 56.5 Years STANDARD_DEVIATION 10.2 | 58.3 Years STANDARD_DEVIATION 10.4 | 56.5 Years STANDARD_DEVIATION 10.1 | 55.7 Years STANDARD_DEVIATION 11 | 56.7 Years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 71 Participants | 9 Participants | 7 Participants | 12 Participants | 9 Participants | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 559 Participants | 62 Participants | 62 Participants | 58 Participants | 61 Participants | 64 Participants | 63 Participants | 62 Participants | 63 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Glycosylated haemoglobin (HbA1c) | 7.89 Percentage of HbA1c STANDARD_DEVIATION 0.73 | 8.00 Percentage of HbA1c STANDARD_DEVIATION 0.8 | 7.77 Percentage of HbA1c STANDARD_DEVIATION 0.71 | 7.77 Percentage of HbA1c STANDARD_DEVIATION 0.75 | 7.96 Percentage of HbA1c STANDARD_DEVIATION 0.73 | 8.05 Percentage of HbA1c STANDARD_DEVIATION 0.75 | 7.86 Percentage of HbA1c STANDARD_DEVIATION 0.69 | 7.80 Percentage of HbA1c STANDARD_DEVIATION 0.7 | 7.80 Percentage of HbA1c STANDARD_DEVIATION 0.62 | 7.99 Percentage of HbA1c STANDARD_DEVIATION 0.72 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 50 Participants | 7 Participants | 10 Participants | 4 Participants | 7 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 47 Participants | 6 Participants | 4 Participants | 7 Participants | 7 Participants | 4 Participants | 4 Participants | 7 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 523 Participants | 57 Participants | 54 Participants | 59 Participants | 54 Participants | 63 Participants | 59 Participants | 57 Participants | 63 Participants | 57 Participants |
| Sex: Female, Male Female | 235 Participants | 31 Participants | 21 Participants | 26 Participants | 29 Participants | 28 Participants | 26 Participants | 26 Participants | 23 Participants | 25 Participants |
| Sex: Female, Male Male | 395 Participants | 40 Participants | 48 Participants | 44 Participants | 41 Participants | 43 Participants | 44 Participants | 43 Participants | 47 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 70 | 0 / 69 | 0 / 70 | 0 / 71 | 0 / 70 | 0 / 70 | 0 / 69 | 0 / 71 |
| other Total, other adverse events | 35 / 70 | 32 / 70 | 37 / 69 | 49 / 70 | 49 / 71 | 42 / 70 | 55 / 70 | 44 / 69 | 34 / 71 |
| serious Total, serious adverse events | 1 / 70 | 2 / 70 | 2 / 69 | 0 / 70 | 1 / 71 | 3 / 70 | 5 / 70 | 2 / 69 | 5 / 71 |
Outcome results
Primary
Change in HbA1c (Glycosylated Haemoglobin)
Change from baseline (week 0) in HbA1c was evaluated at week 26. The endpoint was evaluated 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: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 2.5 mg | Change in HbA1c (Glycosylated Haemoglobin) | -0.88 Percentage of HbA1c | Standard Deviation 0.77 |
| Oral Semaglutide 5 mg | Change in HbA1c (Glycosylated Haemoglobin) | -1.23 Percentage of HbA1c | Standard Deviation 0.79 |
| Oral Semaglutide 10 mg | Change in HbA1c (Glycosylated Haemoglobin) | -1.56 Percentage of HbA1c | Standard Deviation 0.92 |
| Oral Semaglutide 20 mg | Change in HbA1c (Glycosylated Haemoglobin) | -1.70 Percentage of HbA1c | Standard Deviation 0.75 |
| Oral Semaglutide 40 mg | Change in HbA1c (Glycosylated Haemoglobin) | -2.04 Percentage of HbA1c | Standard Deviation 0.9 |
| Oral Semaglutide 40 mg Slow Dose-escalation | Change in HbA1c (Glycosylated Haemoglobin) | -1.76 Percentage of HbA1c | Standard Deviation 0.92 |
| Oral Semaglutide 40 mg Fast Dose-escalation | Change in HbA1c (Glycosylated Haemoglobin) | -1.65 Percentage of HbA1c | Standard Deviation 0.77 |
| Oral Semaglutide 40 mg Pooled | Change in HbA1c (Glycosylated Haemoglobin) | -1.85 Percentage of HbA1c | Standard Deviation 0.86 |
| Subcutaneous Semaglutide 1 mg | Change in HbA1c (Glycosylated Haemoglobin) | -1.85 Percentage of HbA1c | Standard Deviation 0.75 |
| Placebo | Change in HbA1c (Glycosylated Haemoglobin) | -0.40 Percentage of HbA1c | Standard Deviation 0.84 |
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.73, -1.22]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.006995% CI: [-0.69, -0.11]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.18, -0.6]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.47, -0.9]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.68, -1.09]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.89, -1.3]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.72, -1.14]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.64, -1.04]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [-1.85, -1.27]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [0.87, 1.45]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: <0.000195% CI: [0.38, 0.96]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.011695% CI: [0.08, 0.67]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.24495% CI: [-0.12, 0.47]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.797395% CI: [-0.34, 0.26]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.390195% CI: [-0.16, 0.42]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.161295% CI: [-0.09, 0.52]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.266995% CI: [-0.13, 0.46]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.098995% CI: [-0.05, 0.56]Mixed Models Analysis
Comparison: Results are based on the data from the on-treatment without rescue medication observation period. The analysis was based on mixed model for repeated measurements with treatment, stratum and country as fixed factors and baseline value as covariate, all nested within visit. Group mean estimates were adjusted according to observed baseline distribution.p-value: 0.556595% CI: [-0.21, 0.39]Mixed Models Analysis
Secondary
Change in Body Mass Index (BMI)
Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. The endpoint was evaluated 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: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 2.5 mg | Change in Body Mass Index (BMI) | -0.67 kg/m^2 | Standard Deviation 0.98 |
| Oral Semaglutide 5 mg | Change in Body Mass Index (BMI) | -0.98 kg/m^2 | Standard Deviation 1.14 |
| Oral Semaglutide 10 mg | Change in Body Mass Index (BMI) | -1.72 kg/m^2 | Standard Deviation 1.44 |
| Oral Semaglutide 20 mg | Change in Body Mass Index (BMI) | -1.93 kg/m^2 | Standard Deviation 1.87 |
| Oral Semaglutide 40 mg | Change in Body Mass Index (BMI) | -2.37 kg/m^2 | Standard Deviation 1.58 |
| Oral Semaglutide 40 mg Slow Dose-escalation | Change in Body Mass Index (BMI) | -2.04 kg/m^2 | Standard Deviation 1.45 |
| Oral Semaglutide 40 mg Fast Dose-escalation | Change in Body Mass Index (BMI) | -2.92 kg/m^2 | Standard Deviation 1.93 |
| Oral Semaglutide 40 mg Pooled | Change in Body Mass Index (BMI) | -2.32 kg/m^2 | Standard Deviation 1.04 |
| Subcutaneous Semaglutide 1 mg | Change in Body Mass Index (BMI) | -0.43 kg/m^2 | Standard Deviation 0.94 |
Secondary
Change in Body Weight
Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated 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: Week 0, Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 2.5 mg | Change in Body Weight | -2.01 kg | Standard Deviation 3.08 |
| Oral Semaglutide 5 mg | Change in Body Weight | -2.89 kg | Standard Deviation 3.32 |
| Oral Semaglutide 10 mg | Change in Body Weight | -4.90 kg | Standard Deviation 4.04 |
| Oral Semaglutide 20 mg | Change in Body Weight | -5.75 kg | Standard Deviation 5.63 |
| Oral Semaglutide 40 mg | Change in Body Weight | -6.91 kg | Standard Deviation 4.57 |
| Oral Semaglutide 40 mg Slow Dose-escalation | Change in Body Weight | -5.93 kg | Standard Deviation 4.34 |
| Oral Semaglutide 40 mg Fast Dose-escalation | Change in Body Weight | -8.29 kg | Standard Deviation 5.27 |
| Oral Semaglutide 40 mg Pooled | Change in Body Weight | -6.71 kg | Standard Deviation 3.18 |
| Subcutaneous Semaglutide 1 mg | Change in Body Weight | -1.16 kg | Standard Deviation 2.59 |
Secondary
Change in Waist Circumference
Change from baseline (week 0) in waist circumference was evaluated at week 26. The endpoint was evaluated 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: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 2.5 mg | Change in Waist Circumference | -2.00 cm | Standard Deviation 4.31 |
| Oral Semaglutide 5 mg | Change in Waist Circumference | -2.29 cm | Standard Deviation 4.54 |
| Oral Semaglutide 10 mg | Change in Waist Circumference | -5.28 cm | Standard Deviation 5.55 |
| Oral Semaglutide 20 mg | Change in Waist Circumference | -4.08 cm | Standard Deviation 4.01 |
| Oral Semaglutide 40 mg | Change in Waist Circumference | -5.71 cm | Standard Deviation 4.65 |
| Oral Semaglutide 40 mg Slow Dose-escalation | Change in Waist Circumference | -4.86 cm | Standard Deviation 5.48 |
| Oral Semaglutide 40 mg Fast Dose-escalation | Change in Waist Circumference | -6.24 cm | Standard Deviation 4.71 |
| Oral Semaglutide 40 mg Pooled | Change in Waist Circumference | -6.34 cm | Standard Deviation 4.65 |
| Subcutaneous Semaglutide 1 mg | Change in Waist Circumference | -2.29 cm | Standard Deviation 3.99 |
Secondary
Number of Confirmed Hypoglycaemic Episodes Recorded
Treatment-emergent confirmed hypoglycaemic episodes were recorded during weeks 0-31 (26 weeks treatment period + 5 weeks 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. Confirmed hypoglycaemic episode is an episode that is severe according to the American Diabetes Association (ADA) classification or plasma glucose value \<3.1 mmol/L with or without symptoms consistent with hypoglycaemia.
Time frame: Weeks 0-31
Population: Overall number of participants analyzed = SAS which comprised all participants exposed to at least 1 dose of randomised semaglutide or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Semaglutide 2.5 mg | Number of Confirmed Hypoglycaemic Episodes Recorded | 4 Episodes |
| Oral Semaglutide 5 mg | Number of Confirmed Hypoglycaemic Episodes Recorded | 4 Episodes |
| Oral Semaglutide 10 mg | Number of Confirmed Hypoglycaemic Episodes Recorded | 6 Episodes |
| Oral Semaglutide 20 mg | Number of Confirmed Hypoglycaemic Episodes Recorded | 1 Episodes |
| Oral Semaglutide 40 mg | Number of Confirmed Hypoglycaemic Episodes Recorded | 1 Episodes |
| Oral Semaglutide 40 mg Slow Dose-escalation | Number of Confirmed Hypoglycaemic Episodes Recorded | 3 Episodes |
| Oral Semaglutide 40 mg Fast Dose-escalation | Number of Confirmed Hypoglycaemic Episodes Recorded | 1 Episodes |
| Oral Semaglutide 40 mg Pooled | Number of Confirmed Hypoglycaemic Episodes Recorded | 6 Episodes |
| Subcutaneous Semaglutide 1 mg | Number of Confirmed Hypoglycaemic Episodes Recorded | 5 Episodes |
Secondary
Number of Treatment Emergent Adverse Events (TEAEs) Recorded
TEAEs were recorded during weeks 0-31 (26 weeks treatment period+5 weeks 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 0-31
Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all participants exposed to at least 1 dose of randomised semaglutide or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Semaglutide 2.5 mg | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 142 Events |
| Oral Semaglutide 5 mg | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 169 Events |
| Oral Semaglutide 10 mg | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 233 Events |
| Oral Semaglutide 20 mg | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 289 Events |
| Oral Semaglutide 40 mg | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 230 Events |
| Oral Semaglutide 40 mg Slow Dose-escalation | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 233 Events |
| Oral Semaglutide 40 mg Fast Dose-escalation | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 245 Events |
| Oral Semaglutide 40 mg Pooled | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 218 Events |
| Subcutaneous Semaglutide 1 mg | Number of Treatment Emergent Adverse Events (TEAEs) Recorded | 127 Events |
Secondary
Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol)
Participants who achieved HbA1c \<7.0%, was evaluated at week 26. The endpoint was evaluated 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: After 26 weeks of treatment
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 2.5 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 27 Participants |
| Oral Semaglutide 2.5 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 29 Participants |
| Oral Semaglutide 5 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 50 Participants |
| Oral Semaglutide 5 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 8 Participants |
| Oral Semaglutide 10 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 49 Participants |
| Oral Semaglutide 10 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 8 Participants |
| Oral Semaglutide 20 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 41 Participants |
| Oral Semaglutide 20 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 7 Participants |
| Oral Semaglutide 40 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 42 Participants |
| Oral Semaglutide 40 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 4 Participants |
| Oral Semaglutide 40 mg Slow Dose-escalation | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 5 Participants |
| Oral Semaglutide 40 mg Slow Dose-escalation | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 47 Participants |
| Oral Semaglutide 40 mg Fast Dose-escalation | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 6 Participants |
| Oral Semaglutide 40 mg Fast Dose-escalation | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 38 Participants |
| Oral Semaglutide 40 mg Pooled | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 45 Participants |
| Oral Semaglutide 40 mg Pooled | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 3 Participants |
| Subcutaneous Semaglutide 1 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Yes | 18 Participants |
| Subcutaneous Semaglutide 1 mg | Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | No | 33 Participants |