Diabetes and Endocrinology

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

Opioid-Induced Adrenal Insufficiency

Erin Blanchette — Wed, 22 May 2024 23:12:22 +0000

Date Added:

May 22, 2024

Journal/Publication:

JAMA International Medicine

Publisher:

American Medical Association

Publication Date:

May 13, 2024

URL:

Opioid-Induced Adrenal Insufficiency

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2024.0687

Keywords

Opioid-Related Disorders

Opioid Use

Hyponatremia

Methicillin-Resistant Staphylococcus aureus

methadone

opioids

Endocrinology

Diabetes and Endocrinology

PMID (1):

38739374

MeSH

opioid-related disorders

Hyponatremia

Methicillin-Resistant Staphylococcus aureus

methadone

Chronic use of opioids can result in suppression of the hypothalamic, pituitary, adrenal axis causing adrenal insufficiency in up to 15% of patients. James W. Mold, MD, MPH

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A woman in her 40s with opioid use disorder receiving methadone (70 mg daily) was admitted for extended antibiotic treatment for methicillin-resistant Staphylococcus aureus bacteremia. She had been taking methadone at varying doses (ranging from 15 to 70 mg daily) for 15 years.

Following the resolution of bacteremia, she experienced unexplained persistent hyponatremia (129 mEq/L) and dizziness, with her urine sodium levels exceeding 40 mEq/L. A high dose, 250-μg cosyntropin stimulation test was performed, which revealed her cortisol levels were 6.6, 17.2, and 19.2 μg/mL (to convert to nmol/L, multiply by 27.6) at baseline, 30 minutes, and 60 minutes, respectively. A serum adrenocorticotropic hormone (ACTH) level was not measured.

Author/s:

Douglas Rice, Hirofumi Yoshida

Management of Outpatients With Diabetes at High Risk of Hypoglycemia

Erin Blanchette — Tue, 26 Mar 2024 16:29:29 +0000

Date Added:

March 26, 2024

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 14, 2024

URL:

Management of Outpatients With Diabetes at High Risk of Hypoglycemia

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.1137

Keywords

diabetes

Diabetes and Endocrinology

Endocrinology

insulin

PMID (1):

38483370

MeSH

diabetes mellitus

diabetes mellitus, type 2

dipeptidyl-peptidase IV inhibitors

diabetes mellitus, type 1

blood glucose

Hypoglycemia

Insulins

Guidance for management of diabetes in patients at risk of hypoglycemia. James W. Mold, MD, MPH

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More than 30 million people in the US have diabetes, approximately 5% with type 1 and approximately 95% with type 2. About 5 million individuals in the US with type 2 diabetes use insulin and 7 million take sulfonylureas; both of these medications have a greater association with hypoglycemia than metformin, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium-glucose cotransporter 2 inhibitors. Each month, 70% of people with type 1 diabetes experience some degree of hypoglycemia.1 Level 1 hypoglycemia is defined as blood glucose of 54 to 70 mg/dL; level 2 is less than 54 mg/dL; and severe hypoglycemia (level 3) occurs when low blood glucose levels cause neurologic or physical symptoms that require help from others. Furthermore, recurrent severe hypoglycemia increases risk of future dementia.2 Hypoglycemia occurs more often in people with lower education, lower income, and food insecurity.3 This synopsis focuses on outpatient management of diabetes with high risk of hypoglycemia; the guideline also addresses prevention of hypoglycemia in hospitalized patients.4

Author/s:

Celeste C Thomas, Karishma Chopra, Andrew M Davis