GLP-1 receptor agonists likely have little or no effect on obesity-related cancer risk

Embargoed for release until 5:00 p.m. ET on Monday 8 December 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. GLP-1 receptor agonists likely have little or no effect on obesity-related cancer risk

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02237

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A systematic review and meta-analysis evaluated the risk for obesity-related cancer associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D) or overweight or obesity. The review found that GLP-1RAs probably have little or no effect on risk for thyroid, pancreatic, breast, or kidney cancer and may have little or no effect on other obesity-related cancers, although certainty of evidence was low for most outcomes. Longer-term studies are needed to clarify potential risks or benefits. The findings are published in Annals of Internal Medicine.

Researchers from Harvard Medical School and colleagues analyzed 48 placebo-controlled randomized controlled trials (RCTs) involving 94,245 participants that evaluated the efficacy or safety of GLP-1RAs/dual agonists in adult patients with T2DM or overweight or obesity that reported on any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma. RCTs included in the review examined only clinically available and FDA-approved agents such as semaglutide, dulaglutide, and tirzepatide. Most studies had short follow-up and were not designed to assess cancer as a primary outcome. The researchers found that GLP-1RAs probably have little or no effect on risk for thyroid, pancreatic, breast, or kidney cancer. For other obesity related cancers such as colorectal, esophageal, and liver cancer, the evidence was of low certainty, and the effect of GLP-1RAs on gastric cancer remains very uncertain. Subgroup and sensitivity analyses showed consistent results across drug classes, doses, and follow-up durations. The findings offer insights into the safety of GLP-1RAs and suggest no clear signal of increased cancer risk, but longer-term studies with cancer-specific end points are needed to clarify potential risks or protective effects.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Cho-Han Chiang, MD, MMSc please email chiangchohan1129@gmail.com.

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2. Methadone in primary care linked to better health care access and sustained treatment retention

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-01764

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-04733

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A randomized controlled trial evaluated whether delivering methadone for opioid use disorder (OUD) in primary care settings improves access to recommended health services compared with specialty addiction clinics in Ukraine. The trial found that integration of methadone into primary care, supported by telementoring, significantly increased adherence to guideline-concordant care while maintaining methadone retention rates. The findings underscore the potential of primary care-based models to address complex health needs. The study is published in Annals of Internal Medicine. 

Researchers from Yale University and the Ukrainian Institute on Public Health Policy randomly assigned 1,459 adults with OUD across 13 Ukrainian cities to receive methadone in either primary care centers or specialty clinics. The primary outcome was the difference in access to 17 recommended services at 24 months. These services included blood pressure measurement, breast, cervical and prostate cancer screenings, testing for HIV, TB, hepatitis B and C viruses, and services for those living with HIV and OUD. The researchers found that patients receiving methadone in primary care settings reported accessing 1 to 2 additional recommended services on average compared those in the specialty clinic group. Primary care centers had higher percentages of cancer, HIV, HCV, and hepatitis B virus screenings at 24 months compared with specialty clinics. Methadone retention at 24 months was similar between groups. Allowing take-home methadone prescription-rather than requiring daily supervised dosing-and prescribing doses above 85 mg were defined as indicators of high-quality care. The frequency of both measures increased across study arms. These findings suggest that integrating methadone treatment into primary care can expand access to preventive and chronic care services without compromising OUD treatment quality, offering a scalable model for low- and middle-income countries with high burdens of OUD. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Eteri Machavariani please email Colleen Moriarty at colleen.moriarty@yale.edu.   

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3. Researchers report novel and promising treatment for fibrosing mediastinitis

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-01764

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A new case report published in Annals of Internal Medicine describes a novel approach for treating fibrosing mediastinitis using rituximab injections directly into mediastinal lymph nodes combined with pulmonary artery angioplasty. Fibrosing mediastinitis is a rare condition characterized by excessive fibrous tissue growth in the mediastinum, often causing airway and vascular compression. Traditional interventions, such as stenting or angioplasty, provide temporary relief but have high restenosis rates, and systemic rituximab has been associated with infectious complications.

Researchers from Beijing Chao-Yang Hospital detail the case of a 60-year-old woman with a decade-long history of exertional dyspnea and chest tightness after occupational exposure to iron dust. Imaging revealed pulmonary hypertension and right middle lobe atelectasis due to mediastinal compression. After biopsy confirmed fibrosing mediastinitis, the care team administered two courses of rituximab injections into hypermetabolic lymph nodes under endoscopic ultrasound guidance. Two months after the second injection, CT scans showed resolution of atelectasis, PET-CT demonstrated reduced metabolic activity, and the patient’s 6-minute walk distance improved from 0 to 230 meters. Subsequently, balloon angioplasty of severely stenotic pulmonary arteries further improved hemodynamics, reducing mean pulmonary artery pressure and increasing walk distance. Lung function also improved significantly. The only adverse event was influenza, managed successfully. To the author’s knowledge, this is the first reported case of lymph node–targeted rituximab for fibrosing mediastinitis. The authors note that further studies are needed to confirm safety and efficacy of this novel approach.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Yuan Hua Yang, MD please email yyh1031@sina.com.

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4. Global consensus outlines legal and ethical principles for AI integration in gastrointestinal endoscopy

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03415

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The World Endoscopy Organization has issued an international consensus statement addressing legal, ethical, and equity considerations for the use of artificial intelligence (AI) in gastrointestinal (GI) endoscopy. The statement emphasizes robust data governance, clear medicolegal frameworks, and strategies to mitigate bias in AI deployment. The consensus is published in Annals of Internal Medicine.

To inform the recommendations, 14 experts from 11 countries participated in a two-round Delphi process as part of the OperA (Optimising Colorectal Cancer Prevention through Personalized Treatment with Artificial Intelligence) project funded by the European Commission. The panel reached consensus on 10 statements grouped into three domains:

• Data governance: AI systems should comply with local data protection regulations, ensure patient privacy through anonymization, and maintain transparency in algorithm updates and performance reporting.
• Medicolegal implications: Physicians must use AI tools within accepted clinical standards and manufacturer guidance. Professional societies should provide clear liability guidance for AI-assisted diagnosis, automated reporting, and emerging performance metrics.
• Equity and bias: AI algorithms should be validated on diverse data sets, with transparent reporting of demographic characteristics, and research should assess whether AI adoption risks widening health disparities.

This consensus provides a foundation for developing guidelines and regulatory frameworks to support responsible AI adoption in GI endoscopy.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Omer F. Ahmad, MBBS, PhD please email Laura Hannam at l.hannam@ucl.ac.uk.   

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5. Novel mpox variant incubation period is slightly longer than previous variants

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-01016

URL goes live when the embargo lifts              

An analysis of clinical surveillance data estimated the incubation period of Mpox virus (MPXV) clade Ib, a new MPXV subclade estimated to have emerged in September 2023 in the Democratic Republic of Congo (DRC). The analysis found that the median incubation period of MPXV clade Ib is 13.5 days, with incubation periods differing by route of disease transmission. These findings have important implications for outbreak management, including flexible and locally adapted public health responses. The report is published in Annals of Internal Medicine.  

Researchers from Johns Hopkins University and colleagues analyzed surveillance data collected between June and October 2024 from the Mpox Treatment Center (MTC) in the Uvira health zone in South Kivu province, eastern DRC, the epicenter of the mpox clade Ib global outbreak. Of 243 suspected cases, the researchers identified 92 polymerase chain reaction (PCR)-confirmed cases of MPXV clade Ib. Of these, 37 were considered high-confidence confirmed cases based on their low cycle threshold (Ct) values. Among confirmed cases, the median time from most recent contact to rash onset was 10 days, 9 days to fever onset, and 9 days to any symptoms, with similar times for high-confidence and suspected cases. When restricting analyses to high-confidence confirmed cases, the median time from exposure to rash onset was estimated to be 13.6 days. The median rash incubation period was shorter for sexual (10.5 days) versus nonsexual (13.5 days) transmission. The findings suggest that the current 3-week monitoring period recommended by the WHO may be insufficient for a portion of clade Ib nonsexually transmitted infections, potentially leading to missed cases and ongoing transmission. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Espoir Bwenge Malembaka, MD, PhD please email ebwenge1@jhu.edu. 

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6. Experts debate management strategies for a diabetic patient with a severe foot infection

This “Beyond the Guidelines” feature is based on a discussion held at the Beth Israel Deaconess Medical Center Grand Rounds on 20 June 2025.

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-04326

URL goes live when the embargo lifts             

In a new Annals Beyond the Guidelines feature, two specialists debate the optimal management of a 49-year-old woman with diabetes who presented with a worsening right foot ulcer and systemic symptoms. Foot infections are the leading cause of hospitalization in patients with diabetes and can range from cellulitis to deep tissue involvement including osteomyelitis. Updated 2023 guidelines from the International Working Group on the Diabetic Foot (IWGDF) and the Infectious Diseases Society of America (IDSA) recommend classifying infections by severity using systemic and local symptoms and signs and tailoring antibiotic therapy and surgical intervention accordingly. As such, asking “How would you manage this diabetic patient with a foot infection,” is an important clinical question.

The patient, Ms. M, has a history of recurrent foot infections, prior toe amputations, and immunosuppression following kidney transplantation. She presented with a 2-week history of a right foot ulcer. It began as a small area that gradually became larger and is associated with swelling and pain. She also experienced fatigue, chills, nausea, and sweats. 

The first discussant, Mary T. LaSalvia, MD, MPH, is a member of the Division of Infectious Diseases at Beth Israel Deaconess Medical Center, and an Assistant Professor at Harvard Medical School, Boston, Massachusetts. Dr. LaSalvia interprets Ms. M’s clinical presentation and initial laboratory evaluation to be indicative of severe infection. She recommends hospital admission, urgent surgical debridement, and broad-spectrum intravenous antibiotics covering methicillin-resistant Staphylococcus aureus (MRSA), gram-negative bacilli, and anaerobes. She advises transitioning to culture-directed oral therapy after improvement, with treatment duration ranging from 2 weeks if there is complete resection or no evidence of osteomyelitis to 3 to 6 weeks if there is residual bone involvement. 

The second discussant, Barry I. Rosenblum, DPM, is Associate Chief of the Division of Podiatry at Beth Israel Deaconess Medical Center, and an Assistant Professor of Surgery at Harvard Medical School, Boston, Massachusetts. Dr. Rosenblum agrees with Dr. LaSalvia’s recommendation that hospitalization and surgical intervention are necessary. He emphasizes the importance of debridement for infection control and wound healing. Both experts agree that outpatient care is appropriate for mild or select moderate infections without systemic signs, and that antibiotic therapy should be guided by tissue or bone cultures whenever possible.

All Beyond the Guidelines features include multimedia components and CME/MOC activities published in Annals of Internal Medicine.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To speak with one of the discussants, please contact Kendra McKinnon at Kmckinn1@bidmc.harvard.edu.

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Also new this issue:

Why Opioids Stop Working for Pain: No Free Ride in the Brain

Jane C. Ballantyne, MD; and George F. Koob, PhD

Ideas and Opinion

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03630

A History of American Legal Barriers to Gender-Affirming Care

Thomas M. Freitag, MD, MPP

History of Medicine

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03515