Phase 3 study supports use of canagliflozin for type 2 diabetes in children and adolescents

Embargoed for release until 5:00 p.m. ET on Monday 4 August 2025   

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   
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1. Phase 3 study supports use of canagliflozin for type 2 diabetes in children and adolescents

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-04017

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02805

Summary for Patients: https://www.acpjournals.org/doi/10.7326/ANNALS-24-04017-PS

URL goes live when the embargo lifts             

A phase 3, international, randomized clinical trial assessed the safety and efficacy of canagliflozin for treatment of type 2 diabetes mellitus (T2DM) in children and adolescents. The study found canagliflozin provided significantly greater and clinically meaningful reductions in HbA1c compared with placebo, and the safety profile was like that seen in adults. The results support the use of canagliflozin for T2DM in children and adults, a population where treatment options are very limited. The findings are published in Annals of Internal Medicine. 

Researchers from Johnson & Johnson studied data from 171 children aged 10 to 18 years with T2DM and inadequate glycemic control between 28 July 2017 and 20 September 2023 at 104 sites across 10 countries. Participants were randomly assigned 1:1 to receive either oral canagliflozin (100 mg) or matching placebo once daily. Their HbA1c and estimated glomerular filtration rate (eGFR) were assessed at week 12. At the week 13 visit, participants with week 12 readings of 7% or higher for HbA1c and at least 60 mL/min/1.73 m² for eGFR were randomly assigned again to either continue receiving their original treatment assignment or have their dose uptitrated from 100 mg/d to 300 mg/d or matching placebo. Treatment continued for a total of 52 weeks. The primary efficacy endpoint was change in HbA1c at week 26. Key secondary endpoints included change in HBA1c at week 52, change in fasting plasma glucose, and change in body weight at week 26 and 52. Safety assessments included monitoring for adverse events (AEs) and adverse events of special interest including hypoglycemic events. 

The researchers found that at week 26, participants receiving canagliflozin had significantly greater HbA1c improvement compared to those who received placebo. A sensitivity analysis showed improvement in HbA1c as early as week 6 that was maintained through the end of study treatment. At week 52, a greater proportion of participants receiving canagliflozin had an HBA1c less than 6.5% (MP, 30.9% vs. 15.6%; difference in MP, 15.2 percentage points [CI, 3.4 to 27.1 percentage points]) or less than 7.0% (MP, 47.2% vs. 28.9%; difference in MP, 18.3 percentage points [CI, 6.6 to 30.0 percentage points]). Fasting plasma glucose levels significantly improved at week 26 in participants receiving canagliflozin compared to placebo. The most common treatment-emergent AEs among participants taking canagliflozin were headaches, nasopharyngitis, urinary tract infection, and vomiting. Risk for hypoglycemic events was low, with no sever hypoglycemic events occurring with canagliflozin treatment. The results show that canagliflozin is safe, effective, and well-tolerated among children and adolescents aged 10 to 18 years with T2DM. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Saberi Rana Ali, MD, MPH, please email SAli45@its.jnj.com. 

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2. Study suggests weight loss could help treat and manage hip osteoarthritis

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00045

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02749

Summary for Patients: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00045-PS  

URL goes live when the embargo lifts             

A randomized controlled trial evaluated the efficacy of a weight loss diet added to exercise on the change in hip pain among adults with hip osteoarthritis. The study found that adding a weight loss diet did not change hip pain severity; however, it did benefit secondary outcomes including physical function, body weight, and other measures of pain. The results suggest that weight loss could be a potential treatment option for the management of hip osteoarthritis. The study is published in Annals of Internal Medicine.

Researchers from Sydney Musculoskeletal Health, The Kolling Institute, University of Sydney and colleagues studied data from 101 adults aged 50 or over with hip osteoarthritis, overweight or obesity, and hip pain for three or more months in Melbourne and Sydney, Australia between June 2021 and January 2023, with follow-up until January 2024. Participants were randomly assigned to either exercise only or a very low calorie diet (VLCD) plus exercise. They were then randomly assigned a physiotherapist, and if assigned in the VLCD plus exercise, randomly assigned a dietician. Components of the exercise only group consisted of five consultations with a physiotherapist and a home strengthening exercise program. The VLCD plus exercise group underwent the same exercise components along with six consultations with a dietitian to support them undertaking a ketogenic VLCD. The primary outcome was 6-month change in hip pain severity. Secondary outcomes were reported at 6 and 12 months and included body weight, BMI, and hip pain physical function and hip-related quality of life subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). The researchers found that at 6 months, there was no evidence of a between-group difference in hip pain severity. Similar results were found at 12 months. All secondary outcomes, with the exception of HOOS pain and function, favored VLCD plus exercise at 6 months. However, the benefits of VLCD plus exercise for HOOS pain and function become apparent at 12 months. Additionally, 82% of VLCD plus exercise participants achieved greater than 5% body weight loss versus 16% in exercise only. The findings stimulate further research on clinical topics including whether weight loss can reduce or delay hip joint replacement surgery.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Michelle Hall, PhD, please email michelle.hall@sydney.edu.au.

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3. Nearly 1 in 3 U.S. adults with a disability report persistent loneliness

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00928

URL goes live when the embargo lifts             

A brief research report characterized loneliness severity in two national samples of people with disabilities (PWD). The study found that severe loneliness was highly prevalent in all disability types, with PWD reporting persistent feelings of loneliness at greater rates than the general population. The findings suggest further research is needed to understand drivers of loneliness among PWD. The study is published in Annals of Internal Medicine.  

Researchers from Brown University performed cross-sectional analyses of two samples of working-age U.S. adults (aged 18 to 64 years) using the National Survey on Health and Disability (NSHD). Samples 1 and 2 (S1 and S2) were surveyed between October 2019 and January 2020 and October 2023 and February 2024, respectively. To stratify results by disability type, they created eight disability categories: six “ACS-6” categories derived from the American Community Survey (ACS), an “SSI/SSDI” category based on self-reported enrollment in Supplemental Security Income (SSI) and/or Social Security Disability Insurance (SSDI), and a “Disability Not Classified” category composed of respondents with disability indicated on NSHD eligibility screening but missed by ACS-6 and SSI/SSDI questions. The researchers used the UCLA Loneliness Scale to evaluate loneliness burden. They found that the burden of severe loneliness was 65% (95% CI, 61% to 69%) in S1 and 68% (CI, 62% to 73%) in S2. Across samples and disability categories, rates of “often” responses to LS questions ranged from 18% (CI, 9% to 27%) to 52% (CI, 44% to 60%). The results indicate that the loneliness burden among adults with disabilities is exceptionally high. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Maggie Salinger, MD, MPP, MPH, please email msalinger@brownhealth.org.

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4. Scoping review finds gaps in evidence of human outcomes and harms for engineering infection control interventions

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00577

URL goes live when the embargo lifts  

A scoping review identified and described primary studies evaluating the effects of physical changes to workplaces or equipment designed to prevent or control infection, also known as engineering infection control interventions. The review found substantial heterogeneity in available evidence and identified gaps in evidence including measurement of harms or efficacy outcomes relevant to human-to-human infection transmission. The review is published in Annals of Internal Medicine. 

Researchers from the University of Colorado Anschutz Medical Campus and National Institute for Occupational Safety and Health (NIOSH)/Centers for Disease Control and Prevention (CDC) reviewed findings from 672 studies published between 1929 and 2024 that evaluate the effects of engineering infection control interventions designed to reduce the spread of respiratory infections transmitted through indoor air. They classified engineering infection control components into 2 broad categories: strategies that dilute pathogens or move air (ventilation) and those that directly capture or inactivate pathogens (filters, germicidal ultraviolet light). They categorized studies into three types: human (those evaluating the effect of interventions on infection transmission in humans); sentinel animal (those evaluating the effect of human pathogen transmission in sentinel animals); and 3) environmental (those performed in chamber or real-world settings and examining intervention effects on air or surface microbial loads, particulate matter counts, and tracer gas concentrations). They developed a rating system to assess the value of study outcome measures based on their relevance to infection transmission in humans. The researchers found that 90% of studies were classified as environmental studies and most often measured surrogate outcomes, such as microbes in air samples, rather than direct human infectious outcomes. Studies measuring outcomes in humans were largely observational and conducted in health care settings. Most studies (61%) examined a single engineering control intervention, an the most frequently studied interventions involved pathogen inactivation, pathogen removal via HEPA filters, or air exchange or dilution. Overall, few studies directly examined the effects of engineering control interventions on human-to-human indoor transmission of respiratory pathogens, and even fewer reported on potential harms, such as toxic byproducts.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Lisa Bero, PhD, please email Laura Kelley at laura.kelley@cuanschutz.edu.

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