glucagon-like peptide 1

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

I Am Taking a GLP-1 Weight-Loss Medication—What Should I Know?

Megan George — Thu, 04 Sep 2025 19:54:15 +0000

Date Added:

September 4, 2025

Journal/Publication:

JAMA Internal Medicine

Publication Date:

July 14, 2025

URL:

I Am Taking a GLP-1 Weight-Loss Medication—What Should I Know?

Type:

Patient Education Materials

Format:

Poster

DOI (1):

10.1001/jamainternmed.2025.1133

Keywords

diet

GLP-1

weight loss

PMID (1):

40658429

MeSH

glucagon-like peptide 1

Glucagon-Like Peptide-1 Receptor Agonists

Information for patients about GLP-1 medications. James W. Mold, MD, MPH

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This JAMA Internal Medicine Patient Page describes how glucagon-like peptide-1 (GLP-1) receptor agonists work and what behaviors to adopt while using them.

Author/s:

Farhad Mehrtash, Jody Dushay, JoAnn E. Manson

I Am Taking a GLP-1 Weight-Loss Medication-What Should I Know?

Hope Smashey — Tue, 15 Jul 2025 17:39:40 +0000

Date Added:

July 15, 2025

Journal/Publication:

JAMA Internal Medicine

Publication Date:

July 14, 2025

URL:

I Am Taking a GLP-1 Weight-Loss Medication-What Should I Know?

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jamainternmed.2025.1133

Keywords

Glucagon-Like Peptide 1

PMID (1):

40658429

MeSH

Glucagon-Like Peptide-1 Receptor Agonists

glucagon-like peptide 1

Exenatide

Information for patients who are taking GLP-1 medications for weight loss. James W. Mold, MD, MPH

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This JAMA Internal Medicine Patient Page describes how glucagon-like peptide-1 (GLP-1) receptor agonists work and what behaviors to adopt while using them.

Author/s:

Farhad Mehrtash, Jody Dushay, JoAnn E Manson

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

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.

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

Jeffrey Wilson — Mon, 22 Oct 2018 15:42:39 +0000

Date Added:

November 1, 2018

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

April 17, 2018

Issue:

Volume:

319

Pages:

1580-1591

URL:

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2018.3024

Keywords

SGLT-2 inhibitors

GLP-1 agonists

hypertension

PMID (1):

29677303

MeSH

dipeptidyl-peptidase IV inhibitors

diabetes mellitus, type 2

glucagon-like peptide 1

sodium-glucose transport proteins

While both SGLT-2 inhibitors and GLP-1 agonists reduced both cardiovascular and all-cause mortality compared to controls, their impact was very small (1% or less in both/all cases), probably not enough to be a reason to choose these medications over others, particularly if you are recommending more effective risk reduction strategies like smoking cessation, physical activity, BP reduction, and statins.

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IMPORTANCE:

The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown.

OBJECTIVE:

To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis.

DATA SOURCES:

MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017.

STUDY SELECTION:

Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment.

DATA EXTRACTION AND SYNTHESIS:

Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed.

MAIN OUTCOMES AND MEASURES:

The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia.

RESULTS:

This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]).

CONCLUSIONS AND RELEVANCE:

In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

Author/s:

Zheng, Sean L., Roddick, Alistair J., Aghar-Jaffar, Rochan, Shun-Shin, Matthew J., Francis, Darrel, Oliver, Nick, Meeran, Karim