Semaglutide

Background
Oral semaglutide at a dose of 25 mg may provide an alternative treatment option to injectable semaglutide (2.4 mg) and higher-dose oral semaglutide (50 mg) for persons with overweight or obesity.

Methods
In a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites in four countries, we enrolled persons without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. The participants were randomly assigned in a 2:1 ratio to receive oral semaglutide (25 mg) or placebo once daily, plus lifestyle interventions. The coprimary end points at week 64 were the percent change in body weight and a reduction of 5% or more in body weight; confirmatory secondary end points included reductions in body weight of 10% or more, 15% or more, and 20% or more and the change in the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score.

Results
A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was −13.6% in the oral semaglutide group and −2.2% in the placebo group (estimated difference, −11.4 percentage points; 95% confidence interval, −13.9 to −9.0; P<0.001). Participants in the oral semaglutide group were significantly more likely than those in the placebo group to have body-weight reductions of 5% or more, 10% or more, 15% or more, and 20% or more (P<0.001 for all comparisons) and to have an improved IWQOL-Lite-CT Physical Function score (P<0.001). Gastrointestinal adverse events were more common with oral semaglutide than with placebo (74.0% vs. 42.2%).

Conclusions
Oral semaglutide at a dose of 25 mg once daily resulted in a greater mean reduction in body weight than placebo in participants with overweight or obesity. (Funded by Novo Nordisk; OASIS 4 ClinicalTrials.gov number, NCT05564117.)

Author/s:

Sean Wharton, Ildiko Lingvay, Pawel Bogdanski, Ruben Duque do Vale, Stephan Jacob, Tobias Karlsson, Chaithra Shaji, Domenica Rubino, W. Timothy Garvey

Managing Adverse Effects of Incretin-Based Medications for Obesity

Megan George — Fri, 01 Aug 2025 13:22:15 +0000

Date Added:

August 1, 2025

Journal/Publication:

JAMA Insights

Publication Date:

July 29, 2025

URL:

Managing Adverse Effects of Incretin-Based Medications for Obesity

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.11153

Keywords

Cardiovascular Diseases

overweight

PMID (1):

40728833

MeSH

diabetes mellitus, type 2

Glucagon-Like Peptide-1 Receptor Agonists

cardiovascular diseases

overweight

Gastric Inhibitory Polypeptide

renal insufficiency

Information on how to deal with the side effects of obesity medications. James W. Mold, MD, MPH

View

This JAMA Insights explores optimal strategies for managing the adverse effects associated with incretin-based medications for obesity, including semaglutide and tirzepatide.

Author/s:

Robert F Kushner, Jaime P Almandoz, Domenica M Rubino

What Should I Know About Injectable Weight-Loss Medications?

Erin Blanchette — Tue, 19 Mar 2024 17:42:08 +0000

Date Added:

March 19, 2024

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

March 11, 2024

URL:

What Should I Know About Injectable Weight-Loss Medications?

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jamainternmed.2023.7268

Keywords

Feeding and Eating Disorders

PMID (1):

38466303

MeSH

Liraglutide

diabetes mellitus

diabetes mellitus, type 2

Information for patients regarding injectable medications for weight loss. James W. Mold, MD, MPH

Free full text

View

How Do I Know If Injectable Weight-Loss Medications Are Right for Me?

The decision to start an injectable weight-loss medication is based on several factors. These include weight, medical history, personal preference, and medication cost. Talk with your health care professional about whether these medications are right for you.

Author/s:

Andrew Kraftson, Dina Griauzde

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Devin Evans — Wed, 24 Mar 2021 05:00:00 +0000

Date Added:

March 24, 2021

Journal/Publication:

New England Journal of Medicine

Publication Date:

March 18, 2021

Issue:

Volume:

384

Pages:

989

URL:

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2032183

Keywords

PMID (1):

33567185

MeSH

Once weekly Semaglutide plus lifestyle counseling was much more effective for helping non-diabetic patients lose weight than placebo plus lifestyle counseling at 68 weeks. The results were clinically significant. James W. Mold, MD, MPH

Free full text

View

Background: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

Methods: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.

Results: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).

Conclusions: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

Author/s:

Wilding, John P.H., Batterham, Rachel L., Calanna, Salvatore, Davies, Melanie, Van Gaal, Luc F., Lingvay, Ildiko, McGowan, Barbara M., Rosenstock, Julio, Tran, Marie T.D., Wadden, Thomas A.,, Sean, Yokote, Koutaro, Zeuthen, Niels, Kushner, Robert F., STEP 1 Study Group