overweight

Importance Obesity affects 1 in 5 children and adolescents, increasing the risk of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the few pharmacotherapy options available for this population, necessitating a comprehensive evaluation of efficacy and safety.

Objective To assess the efficacy and safety of GLP-1 RAs in children and adolescents (<18 years) with obesity, prediabetes, or T2D.

Data Sources A systematic search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized clinical trials (RCTs) published from inception until February 28, 2025. Data analysis was completed from January 2025 to April 2025.

Study Selection RCTs comparing GLP-1 RAs to placebo in children and adolescents with obesity, overweight, prediabetes, or T2D with reported safety and efficacy data were included.

Data Extraction and Synthesis Two reviewers independently extracted data on sample size, population, interventions, follow-up, and outcomes. Risk of bias was assessed using version 2 of the Cochrane risk of bias tool (RoB2). Efficacy outcomes (except lipids) were analyzed as estimated treatment differences, lipids as estimated treatment ratios, and safety via rate ratios. A random-effects inverse variance model was used for all outcomes.

Main Outcomes and Measures The primary efficacy outcomes were change in hemoglobin A1c (HbA1c) (in percentage points), fasting glucose (in milligrams per deciliter), body weight (in kilograms), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), BMI z scores or percentiles, BMI standard deviation score (SDS), lipid outcomes, and blood pressure. Exploratory efficacy outcomes included obstructive sleep apnea and metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease. Safety outcomes included gastrointestinal adverse effects (GI AEs), infections, hepatobiliary disorders, suicidal ideation or behaviors, depression, hypoglycemia, and adverse event discontinuations.

Results A total of 18 RCTs (11 in obesity, 6 in T2D, and 1 in prediabetes) with 1402 participants (838 GLP-1 RA users and 564 placebo) were included (mean [range] age, 13.7 [6-17] years; 831 female participants (59.3%); median [IQR] treatment duration, 0.51 [0.25-1.00] years). GLP-1 RAs significantly reduced HbA1c (−0.44%; 95% CI, −0.68% to −0.21%), fasting glucose (−9.92 mg/dL; 95% CI, −16.20 to −3.64), body weight (−3.02 kg; 95% CI, −4.98 to −1.06), BMI (−1.45; 95% CI, −2.40 to −0.49), BMI SDS (−0.20; 95% CI, −0.36 to −0.05), BMI percentile (−7.24%; 95% CI, −12.97% to −1.51%), and systolic blood pressure (−2.73 mm Hg; 95% CI, −4.04 to −1.43) and increased GI AE (log[rate ratio] [RR], 0.75). Other AEs, including suicidal ideation or behaviors, showed no significant differences.

Conclusions and Relevance In this systematic review and meta-analysis of 18 trials, GLP-1 RAs significantly improved glycemic, weight, and cardiometabolic outcomes in children and adolescents with T2D or obesity. Available data over a relatively short follow-up suggested suicidal ideation or behaviors were not significantly different, although GI AEs warrant attention in long-term management.

Author/s:

Pareeta Kotecha, Wenxi Huang, Ya-Yun Yeh

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

Diagnosis and Treatment of Type 2 Diabetes in Adults A Review

Hope Smashey — Tue, 01 Jul 2025 19:34:58 +0000

Date Added:

July 1, 2025

Journal/Publication:

JAMA

Publication Date:

June 23, 2025

URL:

Diagnosis and Treatment of Type 2 Diabetes in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.5956

Keywords

diabetes

type 2 diabetes

treatment

PMID (1):

40549398

MeSH

diabetes mellitus

Type 2

cardiovascular diseases

dipeptidyl-peptidase IV inhibitors

Insulin Resistance

Insulin Secretion

Glucose Tolerance Test

overweight

risk factors

An evidence-based review of the treatment of patients with Type 2 diabetes mellitus. James W. Mold, MD, MPH

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Importance: Type 2 diabetes involves progressive loss of insulin secretion from pancreatic β cells in the setting of insulin resistance and manifests clinically as hyperglycemia. Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally, with estimates ranging from 589 million to 828 million people worldwide. In the US, type 2 diabetes affects approximately 1 in 6 adults.

Observations: Risk factors for type 2 diabetes include older age, family history, overweight or obesity, physical inactivity, gestational diabetes, Hispanic ethnicity, and American Indian or Alaska Native, Asian, or Black race. Diabetes is diagnosed if fasting plasma glucose is greater than or equal to 126 mg/dL, hemoglobin A1C is greater than or equal to 6.5%, or 2-hour glucose during 75-g oral glucose tolerance testing is greater than or equal to 200 mg/dL. Approximately one-third of adults with type 2 diabetes have cardiovascular disease and 10.1% have severe vision difficulty or blindness. The prevalence of type 2 diabetes is 39.2% among patients with kidney failure. Although weight management is an important component of treatment for type 2 diabetes, no specific diet has been proven to be most effective for improving health outcomes. Physical activity can reduce hemoglobin A1C by 0.4% to 1.0% and improve cardiovascular risk factors (ie, hypertension and dyslipidemia). Randomized clinical trials have reported absolute reductions in microvascular disease (3.5%), such as retinopathy and nephropathy, myocardial infarction (3.3%-6.2%), and mortality (2.7%-4.9%), with intensive glucose-lowering strategies (hemoglobin A1C <7%) vs conventional treatment 2 decades after trial completion. First-line medications for type 2 diabetes include metformin and, in patients with cardiovascular or kidney comorbidities or at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is). Common add-on medications include dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RAs, dipeptidyl peptidase-4 inhibitors, sulfonylureas, and thiazolidinediones. Approximately one-third of patients with type 2 diabetes require treatment with insulin during their lifetime. Several randomized clinical trials have demonstrated benefits of specific SGLT2i and GLP-1RA medications compared with placebo for atherosclerotic cardiovascular disease (12%-26% risk reduction), heart failure (18%-25% risk reduction), and kidney disease (24%-39% risk reduction) over 2 to 5 years. Most trial participants with type 2 diabetes were taking metformin. High-potency GLP-1RA and dual GIP/GLP-1RA medications result in weight loss of greater than 5% in most individuals with type 2 diabetes, and weight loss may exceed 10%.

Conclusions: Type 2 diabetes affects up to 14% of the global population and is associated with preventable long-term complications, such as cardiovascular disease, kidney failure, vision loss, and increased mortality. In addition to lifestyle modifications including diet, exercise, and weight management, metformin is generally first-line therapy for attainment of hemoglobin A1C targets. For individuals with type 2 diabetes and cardiovascular or kidney disease or at high cardiovascular risk, guidelines recommend early treatment with SGLT2i and/or GLP-1RA medications.

Author/s:

Rita R Kalyani, Joshua J Neumiller, Nisa M Maruthur, Deborah J Wexler

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

Summary of Revisions: Standards of Medical Care in Diabetes—2020

John Bayhi — Sat, 14 Mar 2020 19:35:38 +0000

Date Added:

March 14, 2020

Journal/Publication:

Diabetes Care

Publisher:

American Diabetes Association

Publication Date:

January 1, 2020

Issue:

Supplement 1

Volume:

Pages:

S4-S6

URL:

Summary of Revisions: Standards of Medical Care in Diabetes—2020

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.2337/dc20-Srev

Keywords

PMID (1):

31862743

MeSH

Sodium-Glucose Transporter 2 Inhibitors

Diabetic Ketoacidosis

Ficus

Glucagon-Like Peptide-1 Receptor

glycated hemoglobin a

cardiovascular diseases

Consensus

Farmers

Cystic Fibrosis

Transients and Migrants

Pharmaceutical Preparations

depression

Smell

Patient Comfort

electronic nicotine delivery systems

Blood Glucose Self-Monitoring

celiac disease

follow-up studies

Latent Autoimmune Diabetes in Adults

seasons

social determinants of health

Standard of Care

Time-to-Treatment

united states food and drug administration

risk reduction behavior

Centers for Disease Control and Prevention

glucagon-like peptide 1

anxiety disorders

Feeding and Eating Disorders

thyroid diseases

Infections

This is a three-page summary of the 2020 updates to the ADA Guidelines for Type 2 diabetes. James W. Mold, MD, MPH

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No abstract available.

Twenty-Four-Hour Movement Guidelines and Body Weight in Youth

John Bayhi — Thu, 20 Feb 2020 18:44:17 +0000

Date Added:

February 20, 2020

Journal/Publication:

The Journal of Pediatrics

Publisher:

Elsevier, Inc.

Publication Date:

January 17, 2020

Issue:

March 2020

Volume:

218

Pages:

204-209

URL:

Twenty-Four-Hour Movement Guidelines and Body Weight in Youth

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/j.jpeds.2019.11.031

Keywords

24-hour healthy movement

PMID (1):

31959469

MeSH

Cross-Sectional Studies

Surveys and Questionnaires

I thought some of you might be interested in seeing or re-reviewing the three 24-hour movement guidelines for children (potentially useful for providing parents with specific/official guidance). James W. Mold, MD, MPH

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Objective

To examine the prevalence of youth meeting the 24-hour healthy movement guidelines (ie, ≥60 minutes of moderate-to-vigorous physical activity, ≤2 hours of screen time, age-appropriate sleep duration), and which combination of meeting these guidelines was most associated with bodyweight status, in a nationally representative US sample.

Study design

Cross-sectional data from the 2016-2017 National Survey of Children's Health were used. A multinomial regression model of body weight status was generated (underweight, overweight, obese vs healthy weight) and then stratified by sex. Analyses were adjusted for potential confounders.

Results

The sample (n = 30 478) was 50.4% female, 52.4% white, and the mean age was 13.85 ± 2.28 years; 15% percent were obese and 15.2% were overweight. Overall, 9.4% met all 3 of the 24-hour healthy movement guidelines, 43.6% met 2, 37.9% met 1, and 9.1% met none. Meeting zero guidelines (vs 3) was associated with the greatest likelihood of overweight (aOR, 1.85; 95% CI, 1.31-2.61), and obesity (aOR, 4.25; 95% CI, 2.87-6.31). Females (aOR, 4.97; 95% CI, 2.59-9.53) had higher odds of obesity than males (aOR, 3.99; 95% CI, 2.49-6.40) when zero (vs 3) guidelines were met. Meeting the moderate-to-vigorous physical activity guideline, either alone or in combination with screen time or sleep duration (vs all 3), was associated with the lowest odds for overweight and obesity in the full sample.

Conclusion

Meeting all movement guidelines was associated with the lowest risk for obesity, particularly in females. Meeting the moderate-to-vigorous physical activity guideline may be a priority to prevent overweight and obesity in youth.

Author/s:

Zhu, X, Healy, S, Haegele, JA, Patterson, F

Effectiveness of Behaviorally Designed Gamification Interventions With Social Incentives for Increasing Physical Activity Among Overweight and Obese Adults Across the United States: The STEP UP Randomized Clinical Trial

Brian Desmarais — Wed, 11 Sep 2019 19:46:36 +0000

Date Added:

September 11, 2019

Journal/Publication:

JAMA Internal Medicine

Publisher:

JAMA

Publication Date:

September 9, 2019

URL:

Effectiveness of Behaviorally Designed Gamification Interventions With Social Incentives for Increasing Physical Activity Among Overweight and Obese Adults Across the United States: The STEP UP Randomized Clinical Trial

Type:

Practice Management Reviews and Guidelines

DOI (1):

10.1001/jamainternmed.2019.3505.

Keywords

weigh loss programs

competition

MeSH

Wearable Electronic Devices

Economics, Behavioral

Goals

motivation

body mass index

Adding competition to a weight loss program enhanced and sustained its effectiveness. James W. Mold, MD, MPH

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IMPORTANCE:

Gamification, the use of game design elements in nongame contexts, is increasingly being used in workplace wellness programs and digital health applications. However, the best way to design social incentives in gamification interventions has not been well examined.

OBJECTIVE:

To assess the effectiveness of support, collaboration, and competition within a behaviorally designed gamification intervention to increase physical activity among overweight and obese adults.

DESIGN, SETTING, AND PARTICIPANTS:

This 36-week randomized clinical trial with a 24-week intervention and 12-week follow-up assessed 602 adults from 40 states with body mass indexes (calculated as weight in kilograms divided by height in meters squared) of 25 or higher from February 12, 2018, to March 17, 2019.

INTERVENTIONS:

Participants used a wearable device to track daily steps, established a baseline, selected a step goal increase, were randomly assigned to a control (n = 151) or to 1 of 3 gamification interventions (support [n = 151], collaboration [n = 150], and competition [n = 150]), and were remotely monitored. The control group received feedback from the wearable device but no other interventions for 36 weeks. The gamification arms were entered into a 24-week game designed using insights from behavioral economics with points and levels for achieving step goals. No gamification interventions occurred during follow-up.

MAIN OUTCOMES AND MEASURES:

The primary outcome was change in mean daily steps from baseline through the 24-week intervention period.

RESULTS:

A total of 602 participants (mean [SD] age, 39 [10] years; mean [SD] body mass index, 30 [5]; 427 [70.9%] male) were included in the study. Compared with controls, participants had a significantly greater increase in mean daily steps from baseline during the intervention in the competition arm (adjusted difference, 920; 95% CI, 513-1328; P < .001), support arm (adjusted difference, 689; 95% CI, 267-977; P < .001), and collaboration arm (adjusted difference, 637; 95% CI, 258-1017; P = .001). During follow-up, physical activity remained significantly greater in the competition arm than in the control arm (adjusted difference, 569; 95% CI, 142-996; P = .009) but was not significantly greater in the support (adjusted difference, 428; 95% CI, 19-837; P = .04) and collaboration (adjusted difference, 126; 95% CI, -248 to 468; P = .49) arms than in the control arm.

CONCLUSIONS AND RELEVANCE:

All 3 gamification interventions significantly increased physical activity during the 24-week intervention, and competition was the most effective. Physical activity was lower in all arms during follow-up and only remained significantly greater in the competition arm than in the control arm.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT03311230.

Author/s:

Patel, M.S., Small, D.S., Harrison, J.D., Fortunato, M.P., Oon, A.L., Rareshide, C.A.L., Reh, G., Szwartz, G., Guszcza, J., Steier, D., Kalra, P., Hilbert V.

The effects of sleep extension on cardiometabolic risk factors: A systematic review

Brian Desmarais — Wed, 19 Jun 2019 20:20:01 +0000

Date Added:

June 19, 2019

Journal/Publication:

The Journal of Sleep Research

Publisher:

European Sleep Research Society

Publication Date:

June 5, 2019

URL:

The effects of sleep extension on cardiometabolic risk factors: A systematic review.

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1111/jsr.12865

Keywords

cardiovascular disease

insulin sensitivity

metabolic syndrome

non-communicable diseases

MeSH

cardiovascular diseases

overweight

Noncommunicable Diseases

Sugars

Insulin Resistance

risk factors

This systematic review found that increasing sleep duration improves direct and indirect measures of insulin sensitivity,

decreased leptin and peptide tyrosine‐tyrosine, and reductions in overall appetite, desire for sweet and salty foods, intake of daily free sugar, and percentage of daily

caloric intake from protein. James W. Mold, MD, MPH

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Studies have shown bidirectional relationships between short- or long-sleep duration and risk for obesity, non-communicable diseases, all-cause mortality and cardiovascular disease mortality. Increasing sleep duration may be an appropriate strategy to reduce cardiometabolic riskin short-sleeping individuals. The aim is to review the effects of sleep extension interventions on cardiometabolic risk in adults. The PubMed and Scopus databases were searched for relevant, English, peer-reviewed scientific publications (until August 2018). Seven studies that aimed to increase sleep duration in adults by any sleep extension intervention and described at least one cardiometabolic risk factor were included. These studies had a combined sample size of 138 participants who were either healthy (n = 14), healthy short-sleeping (n = 92), overweight short-sleeping (n = 10), or pre- or hypertensive short-sleeping (n = 22) individuals. The durations of the sleep extensioninterventions ranged from 3 days to 6 weeks, and all successfully increased total sleep time by between 21 and 177 min. Sleep extensionwas associated with improved direct and indirect measures of insulin sensitivity, decreased leptin and peptide tyrosine-tyrosine, and reductions in overall appetite, desire for sweet and salty foods, intake of daily free sugar, and percentage of daily caloric intake from protein. This review provides preliminary evidence for a role for sleep extension to improve cardiometabolic outcomes and directive towards future studies in the field of cardiometabolic health and sleep.

Author/s:

Henst, R.H.P., Pienaar, P.R., Roden, L.C., Rae, D.E.

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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No abstract available.

Author/s:

Kahan, Scott, Manson, JoAnn E.