weight loss

Celiac disease is an autoimmune disease that can occur through the lifespan and is characterized by immune-mediated enteropathy in response to dietary gluten.1 Celiac disease affects at least 1% of the global population. Important risk factors are a first-degree relative with celiac disease, carrying specific genetic variants, presence of other autoimmune conditions (eg, type 1 diabetes, Hashimoto thyroiditis), and certain chromosomal disorders (eg, Down syndrome, Turner syndrome, Williams syndrome).

Typical gastrointestinal symptoms include diarrhea (38%), abdominal discomfort (34%), and weight loss from malabsorption (16%).2 Subjective improvement in symptoms with a gluten-free diet has a poor positive predictive value (PPV) for celiac disease (36%), making objective testing essential. Diagnostic guidelines (Table) recommend performing serologic testing in individuals with symptoms and/or signs suggestive of celiac disease while they are consuming a diet containing gluten, which is present in wheat, barley, and rye. Gluten reduction or removal from the diet impairs the diagnostic accuracy of screening.3-7 For patients already following a gluten-free diet, gluten consumption must be resumed prior to screening. However, there is no consensus for the dose or duration of gluten consumption that should be maintained through second confirmatory tests. Of the 2 most recent guidelines, one does not specify a dose or duration4 and one suggests at least 3 g per day for at least 6 weeks.3

Author/s:

MD, Marisa G. Stahl, MSCS, Claire Jansson-Knodel

What Is Celiac Disease?

Mary Cervantes — Mon, 17 Aug 2026 17:21:29 +0000

Date Added:

August 17, 2026

Journal/Publication:

JAMA Patient Page

Publisher:

JAMA

Publication Date:

August 12, 2026

URL:

What Is Celiac Disease?

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jama.2026.13079

Keywords

MeSH

Information for patients about celiac disease. James W. Mold, MD, MPH

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Celiac disease is a chronic autoimmune disease caused by consumption of gluten in people with specific genetic markers. Celiac disease affects about 1% of people worldwide and people can start having symptoms at any age. Individuals at increased risk include those with a first-degree relative who has celiac disease and those with autoimmune diseases (eg, type 1 diabetes or Hashimoto thyroiditis) and certain chromosomal conditions (Down syndrome, Turner syndrome, or Williams syndrome).

Author/s:

Kristin L. Walter

Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity

Hope Smashey — Wed, 08 Oct 2025 00:39:43 +0000

Date Added:

October 7, 2025

Journal/Publication:

New England Journal of Medicine

Publication Date:

September 18, 2025

Issue:

Volume:

393

URL:

Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2500969

Keywords

Semaglutide

overweight

PMID (1):

40934115

MeSH

Oral semaglutide 25mg daily resulted in a 14% reduction in weight in 1.4 years. James W. Mold, MD, MPH

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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

Medications for Obesity: A Review

Alex Haga — Sun, 28 Jul 2024 20:47:45 +0000

Date Added:

July 28, 2024

Journal/Publication:

JAMA

Publication Date:

July 22, 2024

URL:

Medications for Obesity: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.10816

Keywords

obesity

weight loss

PMID (1):

39037780

MeSH

obesity

Anti-Obesity Agents

weight loss

A review of available information about currently available medications for weight loss. James W. Mold, MD, MPH

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Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia.

Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16 964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants).

Conclusion and relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.

Author/s:

Kimberly A Gudzune, Robert F Kushner

Interventions for High Body Mass Index in Children and Adolescents: US Preventive Services Task Force Recommendation Statement

Alex Haga — Sun, 28 Jul 2024 20:28:22 +0000

Date Added:

July 28, 2024

Journal/Publication:

JAMA

Publication Date:

July 16, 2024

Issue:

Volume:

332

Pages:

226-232

URL:

Interventions for High Body Mass Index in Children and Adolescents: US Preventive Services Task Force Recommendation Statement

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.11146

Keywords

PMID (1):

38888912

MeSH

adolescent

Body Mass Index*

Pediatric Obesity* / prevention & control

Pediatric Obesity* / therapy

weight loss

The USPSTF recommends intensive interventions to help obese children over 6 lose weight. James W. Mold, MD, MPH

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Importance: Approximately 19.7% of children and adolescents aged 2 to 19 years in the US have a body mass index (BMI) at or above the 95th percentile for age and sex, based on Centers for Disease Control and Prevention growth charts from 2000. The prevalence of high BMI increases with age and is higher among Hispanic/Latino, Native American/Alaska Native, and non-Hispanic Black children and adolescents and children from lower-income families.

Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on interventions (behavioral counseling and pharmacotherapy) for weight loss or weight management in children and adolescents that can be provided in or referred from a primary care setting.

Population: Children and adolescents 6 years or older.

Evidence assessment: The USPSTF concludes with moderate certainty that providing or referring children and adolescents 6 years or older with a high BMI to comprehensive, intensive behavioral interventions has a moderate net benefit.

Recommendation: The USPSTF recommends that clinicians provide or refer children and adolescents 6 years or older with a high BMI (≥95th percentile for age and sex) to comprehensive, intensive behavioral interventions. (B recommendation).

Author/s:

US Preventive Services Task Force, Wanda K Nicholson, Michael Silverstein, John B Wong

Interventions for High Body Mass Index in Children and Adolescents: US Preventive Services Task Force Recommendation Statement

Alex Haga — Sun, 23 Jun 2024 19:40:54 +0000

Date Added:

June 23, 2024

Journal/Publication:

US Preventive Services Task Force

Publication Date:

June 18, 2024

URL:

Interventions for High Body Mass Index in Children and Adolescents: US Preventive Services Task Force Recommendation Statement

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.11146

Keywords

PMID (1):

38888912

MeSH

body mass index

Growth Charts

weight loss

New USPSTF recommendation regarding treatment of obesity in children and adolescents. James W. Mold, MPH

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Population: Children and adolescents 6 years or older.

Author/s:

Wanda K Nicholson, US Preventive Services Task Force, Michael Silverstein, John B Wong, David Chelmow, Tumaini Rucker Coker, Esa M Davis, Katrina E Donahue

Semaglutide vs Endoscopic Sleeve Gastroplasty for Weight Loss

Alex Haga — Tue, 23 Apr 2024 17:53:30 +0000

Date Added:

April 23, 2024

Journal/Publication:

JAMA Netw Open

Publisher:

JAMA Netw Open

Publication Date:

April 1, 2024

Issue:

Volume:

URL:

Semaglutide vs Endoscopic Sleeve Gastroplasty for Weight Loss

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2024.6221

Keywords

PMID (1):

38607627

MeSH

Adult

Gastroplasty

Glucagon-Like Peptides

Midst the hoopla regarding weight loss drugs, don't forget about surgical options. James W. Mold, MD, MPH

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Importance: Obesity is a disease with a large socioeconomic burden. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic bariatric procedure with wide global adoption. More recently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (eg, semaglutide), have attracted increased attention due to their efficacy. However, their cost-effectiveness over an extended period compared with ESG is a critical gap that needs to be better explored for informed health care decision-making.

Objective: To assess the cost-effectiveness of semaglutide compared with ESG over 5 years for individuals with class II obesity.

Design, setting, and participants: This economic evaluation study, conducted from September 1, 2022, to May 31, 2023, used a Markov cohort model to compare ESG and semaglutide, with a no-treatment baseline strategy. The study comprised adult patients in the US health care system with class II obesity (body mass index [BMI] of 35-39.9). The base case was a 45-year-old patient with class II obesity (BMI of 37). Patients undergoing ESG were subjected to risks of perioperative mortality and adverse events with resultant costs and decrement in quality of life.

Interventions: Strategies included treatment with semaglutide and ESG.

Main outcomes and measures: Costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100 000/QALY. A 5-year time horizon with a cycle length of 1 month with a 3% discount rate was used. Probabilities, costs, and quality-of-life estimates of the model were derived from published literature. One-way, 2-way, and probabilistic sensitivity analyses were also performed.

Results: The model found that ESG was more cost-effective than semaglutide over a 5-year time horizon, with an ICER of -$595 532/QALY. Endoscopic sleeve gastroplasty added 0.06 QALYs and reduced total cost by $33 583 relative to semaglutide. The results remained robust on 1-way and probabilistic sensitivity analyses. Endoscopic sleeve gastroplasty sustained greater weight loss over 5 years vs semaglutide (BMI of 31.7 vs 33.0). To achieve nondominance, the annual price of semaglutide, currently $13 618, would need to be $3591.

Conclusions and relevance: This study suggests that ESG is cost saving compared with semaglutide in the treatment of class II obesity. On price threshold analyses, a 3-fold decrease in the price of semaglutide is needed to achieve nondominance.

Author/s:

Haseeb, M., Chhatwal, J., Xiao, J., Jirapinyo, P., Thompson, C.C.

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

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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

Approach to Obesity Treatment in Primary Care: A Review

Erin Blanchette — Tue, 19 Mar 2024 17:28:36 +0000

Date Added:

March 19, 2024

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

March 11, 2024

URL:

Approach to Obesity Treatment in Primary Care: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2023.8526

Keywords

PMID (1):

38466272

MeSH

A review of current recommended primary care approaches for helping patients lose weight and keep it off. James W. Mold, MD, MPH

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Importance: More than 40% of US adults have obesity, which increases the risks for multiple chronic diseases and premature mortality. Historically, nonsurgical interventions often have not led to sufficient weight loss and maintenance to improve health, but highly effective antiobesity medications (AOMs) have recently become available, and additional effective therapeutics are under development. Given that most medical care for adults with obesity is delivered in primary care settings, guidance for integrating weight-management approaches is needed.

Observations: Lifestyle interventions can lead to a mean weight loss of 2% to 9% of initial weight at 1 year and increase the likelihood of weight loss of 5% or more, but weight regain over time is common even with continued treatment. Adjunctive treatments, including AOMs and surgical approaches, can lead to larger, more sustained weight loss and improvements in numerous obesity-associated medical conditions. Highly effective AOMs, including nutrient-stimulated hormone-based therapies, induce mean weight loss of 15% or more. Barriers to intervention, including access to care, have a disproportionate influence on populations most affected by obesity and its consequences.

Conclusions and relevance: Primary care clinicians play a vital role in the assessment, management, and support of patients with obesity. With careful clinical assessment and shared decision-making, a flexible treatment plan can be developed that reflects evidence of treatment efficacy, patient preference, and feasibility of implementation. Adjunctive therapies to lifestyle interventions, including more effective pharmacotherapeutics for obesity, offer hope to patients and the potential for considerable improvements in health and quality of life.

Author/s:

Susan Z Yanovski, Jack A Yanovski

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss

Erin Blanchette — Mon, 12 Feb 2024 17:22:55 +0000

Date Added:

February 12, 2024

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

October 5, 2023

Issue:

Volume:

330

Pages:

1795-1797

URL:

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2023.19574

Keywords

PMID (1):

37796527

MeSH

glucagon-like peptide 1

Estimated rates of various adverse GI events in patients taking GLP1 receptor agonists. James W. Mold, MD, MPH

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This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events.

Author/s:

Mohit Sodhi, Ramin Rezaeianzadeh, Abbas Kezouh, Mahyar Etminan

Stress Incontinence in Women

Bethie Seay — Thu, 08 Jul 2021 05:00:00 +0000

Date Added:

July 8, 2021

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1056/NEJMcp1914037

PMID (1):

34161707

MeSH

Obesity/complications

urinary incontinence, stress/diagnosis

urinary incontinence, stress/etiology

urinary incontinence, stress/surgery

urinary incontinence, stress/therapy

weight loss

A summary of current management recommendations for stress urinary incontinence in women.

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This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.

A 43-year-old woman with a history of obesity (body-mass index [the weight in kilograms divided by the square of the height in meters] of 32.0) reports urinary leakage with coughing, sneezing, and exercise. She first noticed these symptoms after delivering her third child 6 years ago. Since then, her symptoms have worsened, and she now soaks through pads when she runs. She is frustrated by her situation because she would like to exercise to lose weight, but exercise exacerbates her urinary leakage. How should this case be evaluated and managed?

Author/s:

Wu, J. M.

Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174772 participants

Saige Blanchard — Fri, 07 May 2021 05:00:00 +0000

Date Added:

May 7, 2021

Publisher:

The Lancet

Publication Date:

May 6, 2021

URL:

Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174772 participants

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

Keywords

gastric bypass

obesity

proportional hazard models

MeSH

Metabolic bariatric surgery appears to increase life expectancy substantially (6+ years) in patient with or without diabetes.

James W. Mold, MD, MPH

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Summary Background Metabolic–bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy—especially stratified by pre-existing diabetes status—are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic–bariatric surgery versus usual care. Methods We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic–bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic–bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472.

Author/s:

Syn, N.L, Cummings, D. E., Wang, L. Z., Lin, D. J., Zhao, J. J., Loh, M., Koh, Z. J., Chew, C. A., Kim, G., Bok-Yan So, J., Kaplan, L. M., Dixon, J. B., Shabbir, A.

The Key Role of Nonpharmacologic Management of Cachexia in Persons With Advanced Illness: A Teachable Moment

Devin Evans — Thu, 29 Apr 2021 05:00:00 +0000

Date Added:

April 29, 2021

Journal/Publication:

Journal of the American Medical Association Internal Medicine

Publication Date:

April 26, 2021

URL:

The Key Role of Nonpharmacologic Management of Cachexia in Persons With Advanced Illness: A Teachable Moment

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2021.1533

Keywords

weight loss

Colon cancer

oncology

nonpharmacological treatment

Cachexia

PMID (1):

33900359

MeSH

Practical guidance for non-pharmacologic management of cachexia. James W. Mold, MD, MPH

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A man in his 80s with advanced colon cancer and malignant ascites presented to the oncology clinic to discuss next steps. He reported weight loss (approximately 15 kg in 2 months), and his daughter commented on his limited appetite, weakness, and that he was “just bones.” Recent computed tomography staging scans had demonstrated progression of the cancer. On examination, temporal wasting and an indwelling peritoneal catheter were noted.

The oncologist discussed the lack of further meaningful chemotherapy or clinical trial options. The daughter requested that something be done for appetite and weight loss. The patient expressed food aversion. The oncologist prescribed a 2-week supply of megestrol acetate solution for anorexia and/or cachexia. The co-pay was $57. Three days later, the daughter called the oncologist and was distressed because her father was now weaker and bedbound. The patient enrolled in home hospice and died the next day. The daughter expressed guilt that she was unable to nourish her father during his last days.

Author/s:

Kabani, A., Dy, S.M., Gupta, A.

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

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial

Devin Evans — Fri, 26 Feb 2021 06:00:00 +0000

Date Added:

February 26, 2021

Journal/Publication:

Journal of the American Medical Association

Publication Date:

February 24, 2021

URL:

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2021.1831

Keywords

PMID (1):

33625476

MeSH

Once weekly SC injections of Semaglutide in addition to intensive behavior change assistance was twice as effective as the behavior change interventions alone after 68 weeks. James W. Mold, MD, MPH

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Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.

Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity.

Design, setting, and participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30).

Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks.

Main outcomes and measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight.

Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants.

Conclusions and relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings.

Author/s:

Wadden, Thomas A., Bailey, Timothy S., Billings, Liana K., Davies, Melanie, Frias, Juan P., Koroleva, Anna, Lingvay, Ildiko, O'Neil, Patrick M., Runino, Domenica M., Skovgaard, Dorthe, Wallenstein, Signe O.R., Garvey, W. TImothy, STEP 3 Investigators