Pediatrics – Endocrinology
RCT: Liraglutide for Children Aged 6 to <12 Years with Obesity
14 Sep, 2024 | 19:40h | UTCSummary:
A recent phase 3a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine examined the efficacy and safety of liraglutide in children aged 6 to less than 12 years with obesity. Currently, no medications are approved for treating nonmonogenic, nonsyndromic obesity in this age group, making this study particularly noteworthy.
Methods:
- Participants: 82 children with obesity (BMI ≥95th percentile for age and sex).
- Design: Participants were randomized in a 2:1 ratio to receive once-daily subcutaneous liraglutide (up to 3.0 mg) or placebo, alongside lifestyle interventions, over a 56-week treatment period, followed by a 26-week follow-up.
- Primary Endpoint: Percentage change in BMI from baseline to week 56.
- Secondary Endpoints: Percentage change in body weight and the proportion achieving a ≥5% reduction in BMI.
Results:
- BMI Reduction: At week 56, the liraglutide group experienced a mean BMI reduction of –5.8%, compared to a +1.6% increase in the placebo group. The estimated difference was –7.4 percentage points (95% CI, –11.6 to –3.2; P<0.001).
- Body Weight: Mean body weight increased by 1.6% in the liraglutide group versus 10.0% in the placebo group, a difference of –8.4 percentage points (95% CI, –13.4 to –3.3; P=0.001).
- BMI Reduction ≥5%: Achieved by 46% of participants in the liraglutide group versus 9% in the placebo group (adjusted odds ratio, 6.3; 95% CI, 1.4 to 28.8; P=0.02).
- Adverse Events: Reported in 89% of the liraglutide group and 88% of the placebo group. Gastrointestinal events were more common with liraglutide (80% vs. 54%).
Discussion:
While the study suggests that liraglutide can lead to a statistically significant reduction in BMI among children aged 6 to less than 12 years with obesity, several considerations should temper our enthusiasm:
- Sample Size and Diversity: The trial included only 82 participants, with a predominantly White population (72%), which may limit the generalizability of the findings to broader, more diverse populations.
- Duration and Long-Term Effects: The study spanned 56 weeks, with a 26-week follow-up. The long-term efficacy and safety of liraglutide in this age group remain uncertain, particularly concerning growth, development, and potential rebound weight gain after discontinuation.
- Clinical Significance: Although the reduction in BMI was statistically significant, the clinical significance—especially regarding long-term health outcomes and obesity-related comorbidities—is less clear. Obesity is a chronic and relapsing condition, and a modest reduction in BMI may not translate into substantial health benefits without sustained intervention.
- Adverse Events: The high incidence of gastrointestinal adverse events raises questions about the tolerability of liraglutide in young children. Managing these side effects in a pediatric population can be challenging and may affect adherence.
- Lack of Consensus on BMI Reduction: There’s no international consensus on what constitutes a clinically meaningful BMI reduction in children, complicating the interpretation of the results.
Conclusion:
This trial provides preliminary evidence that liraglutide, combined with lifestyle interventions, may help reduce BMI in children under 12 with obesity. However, given the limitations—including small sample size, short duration, and safety concerns—it’s prudent to approach these findings with cautious optimism. More extensive studies with longer follow-up periods and more diverse populations are necessary to fully assess the long-term efficacy and safety of liraglutide in this vulnerable age group.
Takeaway:
While liraglutide shows promise as an adjunct therapy for pediatric obesity, it’s essential to weigh the benefits against the potential risks and uncertainties. Clinicians should continue to prioritize established lifestyle interventions and consider pharmacotherapy on a case-by-case basis, pending further evidence.
Multinational Study | No correlation between Covid-19 and onset of type 1 diabetes in children
8 Aug, 2023 | 13:32h | UTC
Do-it-yourself automated insulin delivery: a health-care practitioner user’s guide
7 Aug, 2023 | 14:44h | UTC
Scientific Statement | Addressing childhood obesity to reduce adult CV risk through lifestyle
27 Jul, 2023 | 13:03h | UTCNews Release: How to stop obese children having heart disease in adulthood – European Society of Cardiology
USPSTF Statement | Evidence lacking for lipid disorders screening in asymptomatic children and adolescents
20 Jul, 2023 | 11:13h | UTCEvidence Report: Screening for Lipid Disorders in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force – JAMA
Patient Page: Screening for Lipid Disorders in Children and Adolescents – JAMA
Commentary: USPSTF: Screening Kids for Lipid Disorders Still Needs More Data – TCTMD
Single Arm Trial | Low-carbohydrate diet improves glycemic control in type 1 diabetes
13 Jul, 2023 | 13:04h | UTCRelated:
Management of Type 1 Diabetes With a Very Low–Carbohydrate Diet – Pediatrics (link to abstract – $ for full-text)
Lower carbohydrate diets for adults with type 2 diabetes – British Journal of Nutrition
Low carbohydrate diet: Insights from a general practice service in patients with type 2 diabetes
Review | Child and adolescent obesity
30 May, 2023 | 11:45h | UTCChild and adolescent obesity – Nature Reviews Disease Primers (if the link is paywalled, try this one)
Commentary on Twitter
A Primer in @DiseasePrimers discusses the epidemiology, mechanisms, diagnosis, prevention and management of obesity in children and adolescents, highlighting patient quality of life and areas for further research. https://t.co/Zpcb4RbH2J pic.twitter.com/uneXxVyTDg
— Nature Portfolio (@NaturePortfolio) May 28, 2023
Current recommendations for the management of pediatric diabetic ketoacidosis
25 May, 2023 | 11:31h | UTC
Graves’ disease in children: an update
25 May, 2023 | 11:18h | UTCGraves’ Disease in Children: An Update – Clinical Medicine Insights: Endocrinology and Diabetes
FDA warns of use of selective androgen receptor modulators (SARMs) among teens, young adults
10 May, 2023 | 16:00h | UTCCommentaries:
FDA issues warning for bodybuilding products marketed to teens, young adults – AAP News
Young Men Are Using Banned ‘SARM’ Supplements to Bulk Up, With Harmful Results – HealthDay
Podcast | Congenital hypothyroidism
6 Apr, 2023 | 13:11h | UTC#78: Congenital Hypothyroidism – The Cribsiders
Analysis | Global coverage and design of sugar-sweetened beverage taxes
5 Apr, 2023 | 12:43h | UTCGlobal Coverage and Design of Sugar-Sweetened Beverage Taxes – JAMA Network Open
Related:
WHO manual on sugar-sweetened beverage taxation policies to promote healthy diets.
M-A: Outcomes following taxation of sugar-sweetened beverages.
Public Policies to Reduce Sugary Drink Consumption in Children and Adolescents – Pediatrics
Cutting back on sugar-sweetened beverages: What works? – Cochrane Library
Sugar-sweetened beverage taxes: Lessons to date and the future of taxation – PLOS Medicine
Banning the promotion of soft drinks could be more effective than a sugar tax – The Conversation
Sugar tax: why health experts want it but politicians and industry are resisting – The Guardian
Commentary on Twitter
With 105 national SSB taxes in effect covering 51% of the world’s population, SSB taxes are no longer a novel policy tool. https://t.co/P0TvIdB4D3
— JAMA Network Open (@JAMANetworkOpen) March 29, 2023
Assessment of childhood short stature: a GP guide
3 Apr, 2023 | 13:28h | UTCAssessment of childhood short stature: a GP guide – British Journal of General Practice (free for a limited period)
Review | Graves’disease in children
22 Mar, 2023 | 13:08h | UTCGraves’ disease: moving forwards – Archives of Disease in Childhood
RCT | Closed-loop insulin delivery system enhances blood sugar control in young children with type 1 diabetes
20 Mar, 2023 | 13:54h | UTCSummary: The study enrolled 102 young children between ages 2 and 5, randomized in a 2:1 ratio to either a closed-loop control system of insulin delivery (“artificial pancreas”) or a standard care comparison group. During the 13 weeks of study follow-up, participants in the artificial pancreas group spent 12% more time within their target blood glucose range compared to the standard care group.
The closed-loop group experienced two cases of severe hypoglycemia, while the standard-care group had one case. In the closed-loop group, one case of diabetic ketoacidosis occurred due to a problem with the insulin pump.
Article: Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes – New England Journal of Medicine (link to abstract – $ for full-text)
News Releases:
Commentary on Twitter
In children 2 to younger than 6 years of age with type 1 diabetes, a closed-loop control system was associated with a greater percentage of time in the target glycemic range than standard care. https://t.co/rAOLXRNuub#pediatrics #T1D pic.twitter.com/Nzwl3aFr1w
— NEJM (@NEJM) March 17, 2023
M-A | Global prevalence of diabetic retinopathy in pediatric type 2 diabetes
20 Mar, 2023 | 13:12h | UTC
Current recommendations for management of pediatric diabetic ketoacidosis
10 Mar, 2023 | 14:38h | UTC
Report | Economic impact of overweight and obesity to surpass $4 trillion by 2035
6 Mar, 2023 | 14:32h | UTCSummary:
A recent report from the World Obesity Federation has issued a warning that the number of people worldwide suffering from overweight or obesity could increase significantly by 2035, surpassing the 50% mark. The report, called the World Obesity Atlas 2023, also highlights the significant economic impact of this trend, estimating that the cost of overweight and obesity could reach $4.32tn annually by 2035, equivalent to almost 3% of the global GDP.
The report also identifies two groups that are particularly at risk: children and individuals from lower-income countries. Childhood obesity is a growing concern, as the report predicts it could double by 2035. Additionally, lower-income countries face a rapid increase in obesity prevalence, with nine out of 10 countries with the greatest expected increases in obesity coming from low or lower-middle income countries.
Report: World Obesity Atlas 2023
News release: Economic impact of overweight and obesity to surpass $4 trillion by 2035
Commentary: Report: Obesity could cost the world over $4 trillion a year by 2035 – STAT
Related:
Report: Tenfold increase in childhood and adolescent obesity in four decades
Global cost of obesity-related illness to hit $1.2tn a year from 2025
The Lancet Series: The Double Burden of Malnutrition
M-A | Sugar-sweetened beverage consumption and weight gain in children and adults
6 Mar, 2023 | 14:04h | UTCNews Release: More evidence that sugary drinks cause weight gain – University of Toronto
Youth-onset type 2 diabetes: the epidemiology of an awakening epidemic
2 Mar, 2023 | 13:01h | UTCYouth-Onset Type 2 Diabetes: The Epidemiology of an Awakening Epidemic – Diabetes Care
RCT | Tight glycemic control did not preserve pancreatic beta cell function in newly diagnosed pediatric type 1 diabetes
27 Feb, 2023 | 13:16h | UTCSummary: The study aimed to determine if intensive diabetes management with an automated insulin delivery system could help preserve pancreatic beta cell function in youth with newly diagnosed type 1 diabetes. The randomized clinical trial included 113 youths aged 7 to 17 years and found that although the mean time in the target range of 70 to 180 mg/dL was 78% in the intensive management group vs. 64% in the standard care group, intensive diabetes management did not affect the decline in pancreatic C-peptide secretion at 52 weeks. The study concluded that near normalization of glucose levels instituted immediately after diagnosis of type 1 diabetes did not preserve pancreatic beta cell function in youth.
Article: Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial – JAMA (free for a limited period)
Editorial: Preserving Pancreatic Beta Cell Function in Recent-Onset Type 1 Diabetes – JAMA (free for a limited period)
Commentary on Twitter
Intensive diabetes management with automated insulin delivery did not affect the decline in pancreatic C-peptide secretion at 52 weeks in youths with newly diagnosed type 1 diabetes. https://t.co/e1n5xagrtv #ATTD2023 pic.twitter.com/C6743BmqyH
— JAMA (@JAMA_current) February 24, 2023
RCT | Verapamil partially preserved pancreatic beta cell function in newly diagnosed pediatric type 1 diabetes
27 Feb, 2023 | 13:14h | UTCSummary: The study aimed to determine whether verapamil could preserve pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes. The randomized clinical trial involved 88 participants who were given either verapamil or placebo once daily for 52 weeks. The study found that C-peptide levels were 30% higher in the verapamil group compared to the placebo group at 52 weeks, and the percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% in the verapamil group compared to 71% in the placebo group. The study also found that verapamil was well tolerated with few adverse events. The results suggest that verapamil may partially preserve stimulated C-peptide secretion in children and adolescents with newly diagnosed type 1 diabetes. However, further studies with patient-relevant outcomes are needed to determine the long-term effectiveness and the optimal length of therapy.
Article: Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial – JAMA (free for a limited period)
Editorial: Preserving Pancreatic Beta Cell Function in Recent-Onset Type 1 Diabetes – JAMA (free for a limited period)
News Release: Verapamil shows beneficial effect on the pancreas in children with newly-diagnosed type 1 diabetes – University of Minnesota
Commentary on Twitter
In youth with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo. https://t.co/m4xbczf93C #ATTD2023 pic.twitter.com/teM0jjh1tT
— JAMA (@JAMA_current) February 24, 2023
M-A | Low-dose insulin infusion is safe and effective in treating diabetic ketoacidosis in children
23 Feb, 2023 | 13:40h | UTCSummary: The article discusses a systematic review and meta-analysis of randomized controlled trials comparing low-dose insulin at 0.05 units/kg/hr to standard dose at 0.1 units/kg/hr for children with diabetic ketoacidosis (DKA). The study found that low-dose insulin infusion is probably as efficacious and safer than standard-dose insulin in treating DKA in children, as it has no effect on the time to resolution of hyperglycemia or acidosis and probably reduces the risk of developing hypokalemia and hypoglycemia. However, the results are limited by imprecision and generalizability to other settings since all studies were performed in a single country. Therefore, further studies are required to identify the optimal insulin dose for children with DKA in terms of safety and effectiveness.
RCT | Outcomes in children of women with type 2 diabetes exposed to metformin vs. placebo during pregnancy
8 Feb, 2023 | 12:32h | UTCOutcomes in children of women with type 2 diabetes exposed to metformin versus placebo during pregnancy (MiTy Kids): a 24-month follow-up of the MiTy randomised controlled trial – The Lancet Diabetes & Endocrinology (link to abstract – $ for full-text)
The introduction of sugary drinks tax in the UK was followed by a drop in obesity cases among children
1 Feb, 2023 | 13:32h | UTCNews Releases:
UK soft drink taxes associated with decreased obesity in girls – PLOS
Commentaries:
UK sugar tax ‘prevents 5,000 cases of obesity in year 6 girls annually’ – The Guardian
Related:
WHO manual on sugar-sweetened beverage taxation policies to promote healthy diets.
M-A: Outcomes following taxation of sugar-sweetened beverages.
Public Policies to Reduce Sugary Drink Consumption in Children and Adolescents – Pediatrics
Cutting back on sugar-sweetened beverages: What works? – Cochrane Library
Sugar-sweetened beverage taxes: Lessons to date and the future of taxation – PLOS Medicine
Banning the promotion of soft drinks could be more effective than a sugar tax – The Conversation
Sugar tax: why health experts want it but politicians and industry are resisting – The Guardian
Commentary from the author on Twitter (thread – click for more)
? 19 months after the UK Soft Drinks Industry Levy (sugar tax) was implemented, we found an 8% relative reduction in obesity levels in 10/11 year old girls. Greatest reductions were found in girls from schools in the most deprived areas https://t.co/pYDHZZJrur
— Dr Nina Rogers (@Nina_Tr_Rogers) January 26, 2023