obesity

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

Arm Position and Blood Pressure Readings: The ARMS Crossover Randomized Clinical Trial

Alex Haga — Wed, 23 Oct 2024 15:12:08 +0000

Date Added:

October 23, 2024

Journal/Publication:

JAMA Internal Medicine

Publication Date:

October 7, 2024

URL:

Arm Position and Blood Pressure Readings: The ARMS Crossover Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2024.5213

Keywords

arm position

blood pressure

measurements

PMID (1):

39373998

MeSH

Arm position has a significant effect on BP measurements. James W. Mold, MD, MPH

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Importance: Guidelines for blood pressure (BP) measurement recommend arm support on a desk with the midcuff positioned at heart level. Still, nonstandard positions are used in clinical practice (eg, with arm resting on the lap or unsupported on the side).

Objective: To determine the effect of different arm positions on BP readings.

Design, setting, and participants: This crossover randomized clinical trial recruited adults between the ages of 18 and 80 years in Baltimore, Maryland, from August 9, 2022, to June 1, 2023.

Intervention: Participants were randomly assigned to sets of triplicate BP measurements with the arm positioned in 3 ways: (1) supported on a desk (desk 1; reference), (2) hand supported on lap (lap), and (3) arm unsupported at the side (side). To account for intrinsic BP variability, all participants underwent a fourth set of BP measurements with the arm supported on a desk (desk 2).

Main outcomes and measures: The primary outcomes were the difference in differences in mean systolic BP (SBP) and diastolic BP (DBP) between the reference BP (desk 1) and the 2 arm support positions (lap and side): (lap or side - desk 1) - (desk 2 - desk 1). Results were also stratified by hypertensive status, age, obesity status, and access to health care within the past year.

Results: The trial enrolled 133 participants (mean [SD] age, 57 [17] years; 70 [53%] female); 48 participants (36%) had SBP of 130 mm Hg or higher, and 55 participants (41%) had a body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or higher. Lap and side positions resulted in statistically significant higher BP readings than desk positions, with the difference in differences as follows: lap, SBP Δ 3.9 (95% CI, 2.5-5.2) mm Hg and DBP Δ 4.0 (95% CI, 3.1-5.0) mm Hg; and side, SBP Δ 6.5 (95% CI, 5.1-7.9) mm Hg and DBP Δ 4.4 (95% CI, 3.4-5.4) mm Hg. The patterns were generally consistent across subgroups.

Conclusion and relevance: This crossover randomized clinical trial showed that commonly used arm positions (lap or side) resulted in substantial overestimation of BP readings and may lead to misdiagnosis and overestimation of hypertension.

Author/s:

Hairong Liu, Di Zhao, Ahmed Sabit

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

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

Eating Family Meals Together at Home

Erin Blanchette — Tue, 26 Mar 2024 16:55:00 +0000

Date Added:

March 26, 2024

Journal/Publication:

JAMA Pediatrics

Publisher:

American Medical Association

Publication Date:

March 25, 2024

URL:

Eating Family Meals Together at Home

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jamapediatrics.2023.6669

Keywords

PMID (1):

38526499

MeSH

child development

child

adolescent

Feeding and Eating Disorders

Feeding and Eating Disorders of Childhood/psychology*

Information for parents regarding the benefits of family meals together. James W. Mold, MD, MPH

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Eating meals at home together as a family is important for both parents and children.

Eating dinner together at least 3 or 4 times per week has positive effects on child development and has been linked to children’s lower rates of overweight and obesity, substance abuse, teen pregnancy, depression, and eating disorders; higher self-esteem; and better academic performance. Eating family meals also has nutritional benefits. Families who eat dinner together eat more fruits and vegetables and fewer fried foods and sugary drinks. Family meals also help adults and children learn to like a variety of foods.

Author/s:

Callie L Brown, Melissa C Kay, Lindsay A Thompson

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

Diagnosis and management of polycystic ovarian syndrome

Erin Blanchette — Mon, 12 Feb 2024 16:38:09 +0000

Date Added:

February 12, 2024

Journal/Publication:

Canadian Medical Association Journal

Publisher:

Canadian Medical Association

Publication Date:

January 28, 2024

Issue:

Volume:

196

Pages:

E85-E94

URL:

Diagnosis and management of polycystic ovarian syndrome

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.231251

Keywords

diagnosis

diagnostic

polycystic ovarian syndrome

PCOS

menstruation

PMID (1):

38286488

MeSH

Polycystic Ovary Syndrome

A concise review of polycystic ovarian syndrome. James W. Mold, MD, MPH

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KEY POINTS

Polycystic ovarian syndrome (PCOS) is a chronic disorder associated with infertility; miscarriage; adverse pregnancy outcomes; and cardiovascular, metabolic, psychological and neoplastic risks.

DIagnosis of PCOS can be made based on the presence of any 2 of menstrual irregularities, clinical or biochemical hyperandrogenism or polycystic ovarian morphology on transvaginal ultrasonography.

Treatment of PCOS may target anovulation, androgen excess, hyperinsulinemia and weight management.

Patients with PCOS should have regular monitoring of their body mass index, blood pressure and metabolic parameters, and should be regularly screened for depression, anxiety and obstructive sleep apnea.

Author/s:

Ebernella Shirin Dason, Olexandra Koshkina, Crystal Chan, Mara Sobel

Axillary and inguinal erythrasma

Bethie Seay — Tue, 05 Oct 2021 05:00:00 +0000

Date Added:

October 5, 2021

Journal/Publication:

CMAJ

Publication Date:

October 4, 2021

Issue:

Volume:

193

Pages:

E1535

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1503/cmaj.210310

A concise review of erythrasma.

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A 50-year-old man presented to the dermatology department with a 1-year history of itchy axillary and groin lesions. He had been treated with a topical antifungal preparation (cyclopyroxolamin), without improvement, by his family physician, who had suspected fungal intertrigo. On physical examination, we observed well-circumscribed, erythematous, brownish, scaly plaques affecting both armpits and the groin area bilaterally (Figure 1). To rule out superficial mycoses, we examined skin scrapings from the infected site under direct microscopy after potassium hydroxide preparation. We did not find any signs of fungal infection and did not isolate any dermatophytes in Sabouraud agar.

Author/s:

Riquelme, R. L., Moyano, E. G.

Screening for Prediabetes and Type 2 Diabetes

Bethie Seay — Thu, 26 Aug 2021 05:00:00 +0000

Date Added:

August 26, 2021

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1001/jama.2021.12531

The U.S. Preventive Services Advisory Committee recommends screening nonpregnant adults aged 35 – 70 with BMI >25 for prediabetes and diabetes. While there is no recommendation regarding how often to screen, they mention that every 3 years seems reasonable based upon the evidence they reviewed.

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IMPORTANCE An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5%
meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older
adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps
because of differences in the definition of prediabetes or the heterogeneity of prediabetes.
Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the
US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver
disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause
of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2
diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of
improving health outcomes.
OBJECTIVE To update its 2015 recommendation, the USPSTF commissioned a systematic
review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic,
nonpregnant adults and preventive interventions for those with prediabetes.
POPULATION Nonpregnant adults aged 35 to 70 years seen in primary care settings who have
overweight or obesity (defined as a body mass index 25 and 30, respectively) and no
symptoms of diabetes.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that screening for
prediabetes and type 2 diabetes and offering or referring patients with prediabetes to
effective preventive interventions has a moderate net benefit.
CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for prediabetes
and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians
should offer or refer patients with prediabetes to effective preventive interventions.
(B recommendation)

Author/s:

US Preventative Services task Force

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.

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

Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial

Brian Desmarais — Thu, 19 Nov 2020 18:03:28 +0000

Date Added:

November 19, 2020

Journal/Publication:

JAMA Network Open

Publication Date:

November 8, 2020

Issue:

Volume:

URL:

Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2020.25850

MeSH

cardiovascular diseases

This large RCT suggests that supplementation with Vit D3 2000 IU daily may reduce the risk of metastatic cancer. James W. Mold, MD, MPH

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Importance Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways.

Objective To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index.

Design, Setting, and Participants VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017.

Interventions Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements.

Main Outcomes and Measures For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations.

Results Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI).

Conclusions and Relevance In this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.

Trial Registration ClinicalTrials.gov Identifier: NCT01169259

Author/s:

Chandler, P.D., Chen, W.Y., Ojala, O.N.

Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial

Brian Desmarais — Tue, 25 Aug 2020 16:39:54 +0000

Date Added:

August 25, 2020

Journal/Publication:

Nutrition & Metabolism

Publication Date:

August 12, 2020

URL:

Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1186/s12986-020-00481-9

MeSH

Absorptiometry, Photon

Glucose Clamp Technique

obesity

Body Composition

Carbohydrate-Restricted

This short-term (8-week) RCT found that 60-75 years old adults with obesity lost a lot more weight and visceral adipose tissue and increased their insulin sensitivity more when following a low carbohydrate diet than when following a low fat diet. James W. Mold, MD, MPH

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Background: Insulin resistance and accumulation of visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) place aging adults with obesity at high risk of cardio-metabolic disease. A very low carbohydrate diet (VLCD) may be a means of promoting fat loss from the visceral cavity and skeletal muscle, without compromising lean mass, and improve insulin sensitivity in aging adults with obesity.

Objective: To determine if a VLCD promotes a greater loss of fat (total, visceral and intermuscular), preserves lean mass, and improves insulin sensitivity compared to a standard CHO-based/low-fat diet (LFD) in older adults with obesity.

Design: Thirty-four men and women aged 60-75 years with obesity (body mass index [BMI] 30-40 kg/m2) were randomized to a diet prescription of either a VLCD (< 10:25:> 65% energy from CHO:protein:fat) or LFD diet (55:25:20) for 8 weeks. Body composition by dual-energy X-ray absorptiometry (DXA), fat distribution by magnetic resonance imaging (MRI), insulin sensitivity by euglycemic hyperinsulinemic clamp, and lipids by a fasting blood draw were assessed at baseline and after the intervention.

Results: Participants lost an average of 9.7 and 2.0% in total fat following the VLCD and LFD, respectively (p < 0.01). The VLCD group experienced ~ 3-fold greater loss in VAT compared to the LFD group (- 22.8% vs - 1.0%, p < 0.001) and a greater decrease in thigh-IMAT (- 24.4% vs - 1.0%, p < 0.01). The VLCD group also had significantly greater thigh skeletal muscle (SM) at 8 weeks following adjustment for change in total fat mass. Finally, the VLCD had greater increases in insulin sensitivity and HDL-C and decreases in fasting insulin and triglycerides compared to the LFD group.

Conclusions: Weight loss resulting from consumption of a diet lower in CHO and higher in fat may be beneficial for older adults with obesity by depleting adipose tissue depots most strongly implicated in poor metabolic and functional outcomes and by improving insulin sensitivity and the lipid profile.

Trial registration: NCT02760641. Registered 03 May 2016 - Retrospectively registered.

Author/s:

Gower, Babara, Goss, Amy, Soleymani, Taraneh, Stewart , Mariah, Pendergrass, May, Lockhart, Mark, Kranz, Olivia, Dowla, Shima, Bush, Nikki, Barry, Valene Garr, Fontaine, Kevin R.