Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 179, No 2

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus (T2DM) and overweight or obesity, but their association with cancer is unclear. Purpose: To investigate the risk for obesity-related cancer associated with GLP-1RAs. Data Sources: PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials from inception to August 2025. Study Selection: Randomized placebo-controlled trials reporting any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma. Data Extraction: Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Odds ratios (ORs) were pooled using random-effects meta-analysis. Data Synthesis: The review included 48 trials involving 94 245 participants. GLP-1RAs probably have little or no effect on risk for thyroid cancer (OR, 1.37 [95% CI, 0.82 to 2.31]; 1 fewer to 9 more cases per 10 000 patients treated), pancreatic cancer (OR, 0.84 [CI, 0.53 to 1.35]; 9 fewer to 6 more per 10 000), breast cancer (OR, 0.95 [CI, 0.60 to 1.49]; 10 fewer to 12 more per 10 000), or kidney cancer (OR, 1.12 [CI, 0.78 to 1.60]; 5 fewer to 13 more per 10 000) (moderate certainty). GLP-1RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty). The effect on gastric cancer is very uncertain. Results were consistent in sensitivity analyses of trials with low risk of bias and studies of semaglutide or tirzepatide and across subgroups stratified by follow-up duration, population, GLP-1RA class, weight loss profile, dose, and duration of action. Limitation: The included trials were not designed to evaluate cancer outcomes and had short follow-up. Conclusion: GLP-1RAs may have little or no effect on risk for obesity-related cancers. Longer-term studies are needed to clarify potential risks or benefits. Primary Funding Source: None. (PROSPERO: CRD42024608365)

In adults aged 50 to 69 y, invitation to screening with FIT was noninferior to invitation for colonoscopy for colorectal cancer mortality at 10 y

Clinical Impact Ratings GIM/FP/GP: 6 out of 7 Gastroenterology: 6 out of 7 Public Health: 7 out of 7

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, with a prevalence of 4% to 10%. It is a chronic condition characterized by abdominal pain in conjunction with altered bowel habits, abdominal distention, or bloating. IBS can present with 3 different defecation patterns: IBS with constipation, IBS with diarrhea, or mixed IBS. Recent advances in IBS include a positive diagnosis based on symptom-based criteria and a treatment plan based on IBS subtype and bothersome symptoms. In addition to diet and lifestyle modifications, this article discusses the role of new pharmacologic and nonpharmacologic treatment options for the management of IBS.

How and When to Use Microbial Restoration Therapies for Clostridioides difficile Infection

Trends in Dispensed Gabapentin Prescriptions in the United States, 2010 to 2024

The Mediterranean Diet for Irritable Bowel Syndrome: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 12

Background: Patients with irritable bowel syndrome (IBS) frequently seek dietary advice, but few evidence-based options exist. Major societal guidelines recommend traditional dietary advice (TDA) as first-line therapy, with the cumbersome and resource-intensive low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet reserved as second-line therapy. Recent pilot data suggest that the Mediterranean diet (MD), renowned for its general health benefits, improves IBS symptoms, but whether it can be considered another first-line dietary option is unknown. Objective: To determine if the MD is noninferior to TDA in managing IBS symptoms. Design: Randomized noninferiority clinical trial. (ClinicalTrials.gov: NCT05985018) Setting: Online virtual platform. Participants: 139 persons with IBS from across the United Kingdom. Intervention: 6 weeks of the MD (n = 68) or TDA (n = 71). Measurements: Primary end point was the proportion achieving clinical response, defined as 50-point or greater reduction in IBS Symptom Severity Scale (IBS-SSS). Secondary outcomes included changes in IBS-SSS scores, psychological health, somatic symptom reporting, quality of life, diet satisfaction, and Mediterranean Diet Adherence Screener (MEDAS). Results: Baseline characteristics (mean age, 40.4 years [range, 19 to 65 years]; 80% women) and IBS-SSS (mean, 309 [SD, 90]) were similar between groups. On modified intention-to-treat analysis, the primary end point was met by 62% (95% CI, 50% to 73%) following a MD versus 42% (CI, 31% to 55%) following TDA. The difference in clinical response favored the MD (difference, 20 percentage points [CI, 4 to 36 percentage points]; P = 0.017), demonstrating noninferiority and superiority. There was a greater reduction in the mean IBS-SSS after a MD than TDA (−101.2 vs. −64.5; Δ−36.7 [CI,−70.5 to −2.8]; P = 0.034). No statistically significant differences were seen between the groups with regard to changes in mood, somatic symptoms, quality of life, or diet satisfaction. The MEDAS significantly increased after a MD compared with TDA (P < 0.001). Limitation: No long-term data. Conclusion: The MD showed noninferiority and superiority to TDA in managing IBS symptoms. It represents a viable first-line dietary intervention for IBS. Primary Funding Source: None.

Guideline recommends antiviral prophylaxis for patients at high risk for HBV reactivation

Clinical Impact Ratings GIM/FP/GP: 5 out of 7 Gastroenterology: 6 out of 7 Infectious Disease: 6 out of 7 Public Health: 6 out of 7

The Risk for Bleeding in Patients With Atrial Fibrillation From Concomitant Use of Apixaban or Rivaroxaban With Diltiazem Compared With Metoprolol

Background: Diltiazem is a potent inhibitor of cytochrome P450 3A4 and P-glycoprotein substrates, which can affect the metabolic pathways of factor Xa inhibitors, predisposing patients with atrial fibrillation (AF) to serious bleeding complications. Objective: To compare the risk for bleeding among patients with AF who used apixaban or rivaroxaban in combination with diltiazem compared with metoprolol. Design: Retrospective cohort active comparator study. Setting: U.S. administrative health care database. Patients: Persons with AF. Intervention: Use of apixaban or rivaroxaban with diltiazem or metoprolol. Measurements: The primary study outcome was a composite of serious bleeding events leading to hospitalization. Secondary study outcomes included composites of stroke or systemic embolism. Diltiazem was stratified by high dose (>120 mg/d) and low dose (≤120 mg/d). Propensity score matching was used to adjust for differences between diltiazem and metoprolol users. Results: In the matched cohort of patients with AF, 23 000 were users of diltiazem and 23 000 were users of metoprolol. After propensity score matching, diltiazem (vs. metoprolol) was associated with a higher risk for bleeding events (rate difference [RD], 5.4 [95% CI, 1.2 to 9.6] per 1000 person-years). The risk for bleeding increased with high- versus low-dose diltiazem (high dose: RD, 9.2 [CI, 2.7 to 15.7]; low dose: RD, 2.6 [CI, 0.5 to 8.0]). The estimated 12- and 6-month risk differences between diltiazem and metoprolol were 0.48 percentage points (CI, 0.09 to 0.83 percentage points) and 0.31 percentage points (CI, 0.04 to 0.58 percentage points), respectively. Limitation: Residual confounding. Conclusion: In commercially insured patients with AF receiving apixaban or rivaroxaban, the use of diltiazem was associated with an increased risk for serious bleeding complications when compared with metoprolol. Primary Funding Source: National Heart, Lung, and Blood Institute.

Impact of Study Hypotheses on Results From Randomized Clinical Trials: Comparison Between Standard and Noninferiority Randomized Clinical Trials

Background: In embarking on randomized clinical trials (RCTs), researchers can hypothesize that a more intensive treatment is better than a less intensive treatment (positive hypothesis) or that a less intensive treatment is similar or noninferior to a more intensive treatment (negative hypothesis). Researchers may design noninferiority RCTs (NI-RCTs) to support negative hypotheses and standard RCTs (S-RCTs) to support negative or positive hypotheses. Regardless of hypotheses, S-RCTs and NI-RCTs should produce consistent results when assessing similar participants, interventions, control, and outcomes. Objective: To compare effect estimates in S-RCTs with positive hypotheses versus NI-RCTs and in S-RCTs with negative hypotheses versus NI-RCTs. Design: Meta-research. Setting: 98 meta-analyses. Participants: 468 RCTs, including 153 NI-RCTs and 315 S-RCTs (149 positive and 166 negative hypotheses). Intervention: S-RCTs as the exposure and NI-RCTs as the control. Measurements: The ratio of effect estimates between S-RCTs and NI-RCTs in each meta-analysis was combined across meta-analyses. Results: Standard RCTs with positive hypotheses produced effect estimates 1.47 (95% CI, 1.27 to 1.70) times larger than NI-RCTs; among RCTs rated as having low risk of bias for blinding, the ratio was 1.01 (CI, 0.70 to 1.45), whereas among those rated as having high or unclear risk of bias for blinding, the ratio was 1.81 (CI, 1.41 to 2.33). Standard RCTs with negative hypotheses did not produce statistically different effect estimates from NI-RCTs (ratio, 0.93 [CI, 0.84 to 1.03]). Limitation: Findings may be limited by residual differences between S-RCTs and NI-RCTs in the same meta-analysis. Conclusion: The researchers’ hypotheses may bias the results of published RCTs, especially those with high or unclear risk of bias for blinding. The effect of researchers’ hypotheses should be assessed in systematic reviews and clinical practice guidelines when RCTs addressing the same clinical question report conflicting hypotheses. Primary Funding Source: The Shenzhen Municipal Government, Guangdong Province, China, and the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences.

Quality Indicators for Screening and Surveillance of Colorectal Cancer in Adults: A Review of Performance Measures by the American College of Physicians

Colorectal cancer is the second leading cause of cancer-related deaths for both men and women. Screening for colorectal cancer is an effective strategy to reduce morbidity and mortality, but uptake remains suboptimal. Several performance measures for colorectal cancer screening and surveillance are currently used in pay-for-performance, public reporting, and/or accountability programs. The American College of Physicians (ACP) embraces performance measurement as a means to improve quality of care. The ACP believes that a performance measure must be methodologically sound and evidence-based to be considered for inclusion in payment, accountability, or reporting programs. These principles are critical given the potential effect to physician administrative work and reputation and reimbursement and to prevent unintended consequences on patient care. The ACP’s Performance Measurement Committee (PMC) reviews performance measures using a validated process to recognize high-quality performance measures, address gaps and areas for improvement in performance measures, and help reduce reporting burden. This article aims to present a review of current performance measures for colorectal cancer screening and surveillance to inform physicians, payers, and policymakers in their selection and use of performance measures and make recommendations for measures that could be developed. The PMC appreciates the importance of colorectal cancer screening in the prevention and early detection of colorectal cancer and supports performance measures based on strong recommendations. The PMC reviewed 5 performance measures for colorectal cancer screening relevant to internal medicine and supports 1 performance measure (“Facility 7-Day Risk-Standardized Hospital Visit Rate after Outpatient Colonoscopy”) for use.