Semaglutide, tirzepatide, and dulaglutide have similar gastrointestinal safety profiles in clinical settings

Embargoed for release until 5:00 p.m. ET on Monday 3 November 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. Semaglutide, tirzepatide, and dulaglutide have similar gastrointestinal safety profiles in clinical settings

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-01724

URL goes live when the embargo lifts             

A new observational study compared the risk for severe gastrointestinal adverse events across dulaglutide, semaglutide, and tirzepatide in patients with type 2 diabetes (T2D). The study found that the medications have similar gastrointestinal safety profiles among those with T2D, providing clinicians with evidence to weigh the risks and benefits of these medications for their patients. The findings are published in Annals of Internal Medicine.  

Prior placebo-controlled randomized controlled trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and tirzepatide have shown that these medications are associated with an increased risk for gastrointestinal-related adverse events; however, whether individual GLP-1 RAs and tirzepatide have different gastrointestinal safety among patients with type 2 diabetes in clinical practice remains unclear. Researchers from Brigham and Women's Hospital and Harvard Medical School and colleagues used data from Optum’s deidentified Clinformatics Data Mart database to emulate three clinic trials of adults with T2D initiating dulaglutide, subcutaneous semaglutide, or tirzepatide between 1 January 2019 and 30 August 2024. They assessed 65,238 matched pairs in the semaglutide versus dulaglutide cohort, 20,893 in the tirzepatide versus dulaglutide cohort, and 46,620 in the tirzepatide versus semaglutide cohort. The primary outcome was a composite of severe gastrointestinal AEs resulting in an inpatient and/or emergency department encounter. The hazard ratio of gastrointestinal events was 0.96 (95% CI, 0.87 to 1.06) in the semaglutide versus dulaglutide cohort, 0.96 (CI, 0.77 to 1.20) in the tirzepatide versus dulaglutide cohort, and 1.07 (CI, 0.90 to 1.26) in the tirzepatide versus semaglutide cohort. These findings were consistent across subgroups and sensitivity analyses. The results align with those seen in head-to-head randomized clinical trials and may help physicians when determining the benefits and risks of prescribing these popular medications. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Elisabetta Patorno, MD, DrPH, please email Meg Montgomery at mmontgomery3@mgb.org. 

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2. Review identifies most effective psychological therapies for perinatal depression

The findings will inform updated clinical practice guidelines on the treatment of perinatal depression

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-03520

URL goes live when the embargo lifts             

A systematic review and meta-analysis evaluated the effectiveness of psychological therapies for perinatal depression, the most prevalent maternal mental health disorder. The review found that cognitive behavioral therapy, behavioral activation, and interpersonal therapy may be more effective at treating perinatal depression than usual care. The results of the review will be used to inform the development of clinical practice guidelines related to the treatment of perinatal depression. The review is published in Annals of Internal Medicine.  

Researchers commissioned by the Agency for Healthcare Research and Quality (AHRQ) and the American College of Obstetricians and Gynecologists (ACOG) analyzed 44 randomized controlled trials (RCTs) of psychological therapies for people with depression during pregnancy and up to one year postpartum published between January 2000 and March 2025. The primary outcomes were the effect of psychological treatments on depressive symptoms and recovery from depressive symptoms. The most studied interventions included cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). The review found that CBT was probably more effective at reducing depression and anxiety symptoms than usual treatment, and there may have been higher rates of recovery with CBT versus usual treatment. Behavioral activation may be more effective at reducing depressive symptoms than usual treatment. Interpersonal therapy (IPT) was probably moderately effective in reducing depressive symptoms compared to usual treatment, and recovery rates may increase with IPT. Overall, CBT, behavioral activation, and IPT may be more effective overall for treating perinatal depression than usual care. However, the researchers note that studies included in the review primarily included White participants with higher educational attainment, so the results may not be applicable to a wider population of people. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Elyse Couch, PhD, please email Juan Siliezar at juan_siliezar@brown.edu.

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3. Albumin-specific measurement more effective at determining kidney disease than total protein measurement

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02117

URL goes live when the embargo lifts             

An individual patient-level meta-analysis assessed and compared the performance of urinary albumin–creatinine ratio (UACR) and urinary protein–creatinine ratio (UPCR) across chronic kidney disease (CKD)-related clinical outcomes. The analysis found that UACR was more strongly associated with development of kidney failure than UPCR, supporting the use of UACR as the preferred measure to stratify patients at risk for CKD-related outcomes. The findings are published in Annals of Internal Medicine. 

Researchers from the Chronic Kidney Disease Prognosis Consortium (CKD-PC) studied data from 148,994 participants in cohorts of the CKD-PC who had UACR and UPCR measured on the same day. Cohorts are eligible to join the CKD-PC if they have sufficient data on kidney function and subsequent clinical outcomes. The researchers quantified the associations of UACR and UPCR with outcomes including incident kidney failure with kidney replacement therapy, myocardial infarction, stroke, heart failure, and cardiovascular death. The researchers found consistent associations for both UACR and UPCR for CKD-related adverse clinical outcomes. However, UACR was more strongly associated than UPCR with incident kidney failure.  For patients with higher baseline UACR, lower estimated glomerular filtration rate (eGFR), diabetes, or glomerulonephritis, the comparative advantage of UACR was particularly strong. Associations with cardiovascular disease-related outcomes were similar for both UACR and UPCR, but subgroups with a higher baseline UACR saw somewhat stronger associations with UACR than with UPCR. The findings support the routine measurement of UACR to risk-stratify patients for CKD-related adverse outcomes. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Shoshana H. Ballew, PhD please email Gregory Williams at Gregory.Williams@nyulangone.org. 

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Also new this issue:

Artificial Intelligence–Assisted Data Extraction With a Large Language Model: A Study Within Reviews

Gerald Gartlehner, MD, MPH, et al.

Research and Reporting Methods

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00739

Overdue: Delayed Revision of Institutional Review Board Policies Characterizing Pregnant Women After the Revised Common Rule

Caleigh Propes, BA; and Stephanie R. Morain, PhD, MPH

Ideas and Opinions

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02499

Revaluing Physician Services: CMS Has Some (but not All) Answers

William Fox, MD

Ideas and Opinions

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03638