overweight

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

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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

Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial

Alex Haga — Thu, 29 May 2025 13:14:00 +0000

Date Added:

May 29, 2025

Journal/Publication:

JAMA

Publication Date:

April 24, 2025

Issue:

Volume:

333

Pages:

1804-1812

URL:

Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2025.3471

Keywords

PMID (1):

40274279

MeSH

Hypoglycemic Agents* / therapeutic use

Metformin* / therapeutic use

Obesity* / complications

osteoarthritis

Knee* / complications

Metformin 2000mg per day appears to reduce the pain of osteoarthritis of the knees in people who are overweight or obese. James W. Mold, MD, MPH

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Importance: Preclinical and preliminary human evidence suggests that metformin, a first-line treatment for type 2 diabetes, reduces inflammation, preserves cartilage, and improves knee pain in knee osteoarthritis.

Objective: To evaluate the effects of metformin on knee pain at 6 months in participants with symptomatic knee osteoarthritis and overweight or obesity.

Design, setting, and participants: Community-based randomized, parallel-group, double-blind, placebo-controlled clinical trial that used telemedicine to recruit and follow up participants remotely. Individuals with knee pain for 6 months or longer, a pain score greater than 40 mm on a 100-mm visual analog scale (VAS), and body mass index of 25 or higher were recruited from the community through local and social media advertisements in Victoria, Australia, between June 16, 2021, and August 1, 2023. Final follow-up occurred on February 8, 2024.

Interventions: Participants were randomly assigned to receive either oral metformin, 2000 mg/d (n = 54), or identical placebo (n = 53) for 6 months.

Main outcomes and measures: The primary outcome was change in knee pain, measured using a 100-mm VAS (score range, 0-100; 100 = worst; minimum clinically important difference = 15) at 6 months.

Results: Of 225 participants assessed for eligibility, 107 (48%) were randomized (mean age, 58.8 [SD, 9.5] years; 68% female) and assigned to receive metformin or placebo. Eighty-eight participants (82%) completed the trial. At 6 months, the mean change in VAS pain was -31.3 mm in the metformin group and -18.9 mm in the placebo group (between-group difference, -11.4 mm; 95% CI, -20.1 to -2.6 mm; P = .01), corresponding to an effect size (standardized mean difference) of 0.43 (95% CI, 0.02-0.83). The most common adverse events were diarrhea (8 [15%] in the metformin group and 4 [8%] in the placebo group) and abdominal discomfort (7 [13%] in the metformin group and 5 [9%] in the placebo group).

Conclusions and relevance: These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.

Author/s:

Feng Pan, Yuanyuan Wang, Yuan Z Lim, Donna M Urquhart

Obesity in Adolescents: A Review

Alex Haga — Sat, 10 Aug 2024 18:21:58 +0000

Date Added:

August 10, 2024

Journal/Publication:

JAMA

Publication Date:

August 5, 2024

URL:

Obesity in Adolescents: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.11809

Keywords

PMID (1):

39102244

MeSH

cardiovascular diseases

diabetes mellitus

diabetes mellitus, type 2

depression

Life Style

exercise

A review of obesity management in adolescents. James W. Mold, MD, MPH

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Importance: Obesity affects approximately 21% of US adolescents and is associated with insulin resistance, hypertension, dyslipidemia, sleep disorders, depression, and musculoskeletal problems. Obesity during adolescence has also been associated with an increased risk of mortality from cardiovascular disease and type 2 diabetes in adulthood.

Observations: Obesity in adolescents aged 12 to younger than 18 years is commonly defined as a body mass index (BMI) at the 95th or greater age- and sex-adjusted percentile. Comprehensive treatment in adolescents includes lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Lifestyle modification therapy, which includes dietary, physical activity, and behavioral counseling, is first-line treatment; as monotherapy, lifestyle modification requires more than 26 contact hours over 1 year to elicit approximately 3% mean BMI reduction. Newer antiobesity medications, such as liraglutide, semaglutide, and phentermine/topiramate, in combination with lifestyle modification therapy, can reduce mean BMI by approximately 5% to 17% at 1 year of treatment. Adverse effects vary, but severe adverse events from these newer antiobesity medications are rare. Surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) for severe adolescent obesity (BMI ≥120% of the 95th percentile) reduces mean BMI by approximately 30% at 1 year. Minor and major perioperative complications, such as reoperation and hospital readmission for dehydration, are experienced by approximately 15% and 8% of patients, respectively. Determining the long-term durability of all obesity treatments warrants future research.

Conclusions and relevance: The prevalence of adolescent obesity is approximately 21% in the US. Treatment options for adolescents with obesity include lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Intensive lifestyle modification therapy reduces BMI by approximately 3% while pharmacotherapy added to lifestyle modification therapy can attain BMI reductions ranging from 5% to 17%. Surgery is the most effective intervention for adolescents with severe obesity and has been shown to achieve BMI reduction of approximately 30%.

Author/s:

Aaron S Kelly, Sarah C Armstrong, Marc P Michalsky, Claudia K Fox

Food Intake Compared to Exercise Association with Obesity in Children Ages 3–6

Aubrey Delammermore — Sat, 07 Jan 2023 06:00:00 +0000

Date Added:

January 7, 2023

Journal/Publication:

Journal of the American Board of Family Medicine

Publisher:

American Board of Family Medicine

Publication Date:

November 17, 2022

Issue:

Volume:

Pages:

1072-1080

URL:

Food Intake Compared to Exercise Association with Obesity in Children Ages 3–6

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.3122/jabfm.2022.220159R1

Keywords

PMID (1):

36396411

MeSH

child, preschool

Pediatric Obesity* / epidemiology

Pediatric Obesity* / etiology

body mass index

exercise

In preschool children, physical activity level was correlated with BMI, and caloric intake was not. James W. Mold, MD, MPH

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Background: Childhood obesity affects 19.3% of children ages 2 to 19 years in the US, and 25.6% of Hispanic children. Study objectives were to (1) assess the feasibility of monitoring physical activity and daily caloric intake in children ages 3 to 6 years, (2) assess whether known obesity risk factors apply to this age-group, and (3) explore the factors that may contribute to the higher prevalence of obesity in Hispanic preschooler.

Methods: Children ages 3 to 6 years were recruited at well child visits (n = 37, 65% male, 30% Hispanic). Parents completed a questionnaire (child’s physical activity and screen time) along with a detailed dietary assessment. Children were provided with a fitness tracker worn for 5 days. Fisher’s exact test, t test/Wilcoxon rank sum tests were conducted.

Results: Thirty-four (92%) participants produced usable activity data. Baseline dietary recall was completed by 35 (97%) of the parents and 25 (68%) completed the second unassisted dietary recall. Mean body mass index of the study sample was 60th percentile, 12 (32%) classified as overweight/obese. Children with overweight/obesity showed no significant difference in mean daily calories compared with those without (1403.9 vs 1406.1 Kcal/day, P = .980) or daily hours of screen time (1.5 ± 1.1 vs 1.7 ± 0.8, P = .442). Children with overweight/obesity had fewer mean daily steps compared with those without overweight/obesity (8038 ± 2685 vs 10038 ± 2599 P = .051).

Discussion: Findings indicate that pedometer activity tracking can be used in children 3 to 6 years old and that decreased physical activity correlates more closely to preschool overweight/obesity than caloric intake.

Author/s:

Bedell, D., Sevcik, T., Daly, J. M., Levy, B. T.

Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity

Aubrey Delammermore — Sat, 24 Sep 2022 05:00:00 +0000

Date Added:

September 24, 2022

Journal/Publication:

JAMA Network Open

Publisher:

American Medical Association

Publication Date:

September 19, 2022

Issue:

Volume:

Pages:

1-11

URL:

Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2022.31982

Keywords

Cohort Studies

overweight

Retrospective Studies

middle aged

weight loss

PMID (1):

36121652

MeSH

Glucagon-Like Peptides

diabetes mellitus

Type 2* / drug therapy

Hypoglycemic Agents / therapeutic use

Obesity / drug therapy

Overweight* / chemically induced

A non-randomized cohort study corroborating approximately 10% reduction in weight with weekly SC Semaglutide. I’m waiting to see if the effect lasts for more than 2 years and how many people are willing and able to continue the drug long term. James W. Mold, MD, MPH

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Importance No retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg).

Objective To study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity.

Design, Setting, and Participants This cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded.

Exposures Weekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months.

Main Outcomes and Measures The primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months.

Results The study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P < .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P < .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months (P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months (P = .005).

Conclusions and Relevance The results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.

Author/s:

Ghusn, W., De la Rosa, A., Sacoto, D.

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

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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

Obesity Treatment, Beyond the Guidelines: Practical Suggestions for Clinical Practice

Tracy Ashby — Fri, 22 Mar 2019 05:00:00 +0000

Date Added:

March 26, 2019

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 21, 2019

URL:

Obesity Treatment, Beyond the Guidelines: Practical Suggestions for Clinical Practice

Type:

Clinical Decision Aids

Format:

Article

DOI (1):

10.1001/jama.2019.2352

Keywords

PMID (1):

30896727

MeSH

This provides some practical clinical advice for primary care clinicians trying to help their patients lose weight and keep it off. James W. Mold, MD, MPH

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Author/s:

Kahan, Scott, Manson, JoAnn E.