Phase 3 · Semaglutide

OASIS 4 trial results

Efficacy and Safety of Oral Semaglutide 25 mg Once Daily in Adults With Overweight or Obesity

Percentage Change in Body Weight (Percentage change in body weight), Baseline (week 0), end of treatment (week 64). Oral Semaglutide 25 mg: -14.4; Placebo: -2.5.

Participants: 307
Status: completed
Completed: 2024-05-07
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT05564117), updated at source Feb 25, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What OASIS 4 measured first

Percentage Change in Body WeightPercentage change in body weight · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=192	Placebon=90
-14.4(10.5)	-2.5(7.9)

Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal to (≥) 5% (Yes/No)Participants · At end of treatment (week 64) · count of participants

Measure	Oral Semaglutide 25 mgn=192	Placebon=90
Yes	152	28
No	40	62

Side effects by arm

Side effects in OASIS 4

Percent of participants affected, From week 0 to week 71. The most common events the registry lists.

Event	Oral Semaglutide 25 mg	Placebo
Any serious event	3.9%	8.8%
Nausea	46.6%	18.6%
Vomiting	30.9%	5.9%
Nasopharyngitis	21.1%	26.5%
COVID-19	20.1%	17.6%
Constipation	20.1%	9.8%
Dyspepsia	18.1%	8.8%
Diarrhoea	17.6%	8.8%
Headache	11.8%	8.8%
Eructation	10.3%	2%
Influenza	7.4%	9.8%
Abdominal pain upper	8.8%	2%
Upper respiratory tract infection	5.4%	8.8%
Gastrooesophageal reflux disease	7.8%	4.9%
Abdominal pain	7.4%	3.9%
Fatigue	7.4%	1%
Bronchitis	4.4%	6.9%
Decreased appetite	6.9%	1%
Sinusitis	3.4%	6.9%
Alopecia	6.4%	2%
Urinary tract infection	6.4%	2.9%
Arthralgia	2.9%	5.9%
Back pain	2.9%	5.9%
Tonsillitis	2.5%	5.9%
Dizziness	5.4%	1%

Secondary outcomes

What else it measured

Number of Participants Who Achieved Body Weight Reduction ≥ 10% (Yes/No)Participants · At end of treatment (week 64) · count of participants

Measure	Oral Semaglutide 25 mgn=192	Placebon=90
Yes	121	13
No	71	77

Number of Participants Who Achieved Body Weight Reduction ≥ 15% (Yes/No)Participants · At end of treatment (week 64) · count of participants

Measure	Oral Semaglutide 25 mgn=192	Placebon=90
Yes	96	5
No	96	85

Number of Participants Who Achieved Body Weight Reduction ≥ 20% (Yes/No)Participants · At end of treatment (week 64) · count of participants

Measure	Oral Semaglutide 25 mgn=192	Placebon=90
Yes	57	3
No	135	87

Change in Physical Function Domain (5-items) Score Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite for CT)Score on a scale · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=188	Placebon=89
16.8(20.4)	8.3(16.7)

Number of Participants Who Achieved ≥14.6 IWQOL-Lite-CT Physical Function Domain (PFD) Score (Yes/No)Participants · Baseline (week 0), end of treatment (week 64) · count of participants

Measure	Oral Semaglutide 25 mgn=188	Placebon=89
Yes	104	31
No	84	58

Change in Body Weight - Kilogram (kg)kg · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=192	Placebon=90
-15.0(11.3)	-2.3(8.2)

Change in Body Mass Index (BMI)Kilogram per square meter (kg/m^2) · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=192	Placebon=90
-5.3(4.0)	-0.9(2.8)

Change in Waist Circumferencecentimeter (cm) · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=191	Placebon=89
-12.9(12.3)	-3.1(11.2)

Change in Systolic Blood PressureMillimeters of mercury (mmHg) · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=192	Placebon=90
-7(15)	-5(15)

Change in Diastolic Blood PressuremmHg · Randomisation (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=192	Placebon=90
-3(9)	-2(10)

Change in Glycosylated Haemoglobin (HbA1c)Percentage of HbA1c · Baseline (week 0), end of treatment (week 64) · mean

Oral Semaglutide 25 mgn=190	Placebon=86
-0.3(0.3)	-0.0(0.2)

Change in Total Cholesterol - Ratio to BaselineRatio of total cholesterol · Baseline (week 0), end of treatment (week 64) · geometric mean

Oral Semaglutide 25 mgn=187	Placebon=87
0.96(15.3)	0.98(16.4)

The trial

How OASIS 4 was run

This study will look how well semaglutide tablets taken once daily helps people with body weight above the healthy range. Participants will either get semaglutide 25 milligram (mg) once daily or placebo once daily. This study will last for 72 weeks, which includes 1-week screening period, 64 weeks of treatment period and 7 weeks of follow up period.

Oral semaglutide 25 mg: Participants will receive semaglutide tablets orally once daily. Participants will receive semaglutide in a dose escalation manner for 64 weeks: 3 mg (weeks 0 to 4), 7 mg (weeks 5 to 8), 14 mg (weeks 9 to 12), and 25 mg (weeks 13 to 64).
Oral semaglutide placebo: Participants will receive placebo tablets matched to semaglutide orally once daily for 64 weeks.

Who could join the trial

Inclusion Criteria: * Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study * Male or female, age greater than or equal to 18 years at the time of signing informed consent * Body mass index (BMI) of * Greater than or equal to 27.0 kg/m\^2 with the presence of at least one of the following weight-related complications (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular (CV) disease OR * Greater than or equal to 30.0 kg/m\^2 * History of at least one self-reported unsuccessful dietary effort to lose body weight Exclusion Criteria: * A self-reported change in body weight greater than 5 kg (11 pound \[lbs\]) within 90 days before screening irrespective of medical records * HbA1c greater than or equal to 6.5 percent (48 mmol/mol) as measured by the central laboratory at screening

Published papers

Papers from OASIS 4

Wharton S, Lingvay I, Bogdanski P, Duque do Vale R, Jacob S, Karlsson T, Shaji C, Rubino D, Garvey WT; OASIS 4 Study Group. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. N Engl J Med. 2025 Sep 18;393(11):1077-1087. doi: 10.1056/NEJMoa2500969.

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.