GLP-1 drugs pose no cancer risk, review finds
A large systematic review and meta-analysis was limited by a median follow-up of 70 weeks.
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12/11/2025
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by Doug Brunk
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) do not appear to increase overall cancer risk based on currently available randomized trial data with a median follow-up of 70 weeks, according to a systematic review and meta-analysis published in Annals of Internal Medicine.
“However, because cancer is a long-latency outcome and the number of events is relatively small in our study, our findings should be viewed as reassuring but not definitive,” one of the study authors, Cho-Han Chiang, MD, of the Department of Medicine and Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, told this news organization in an interview. “Clinicians should continue to individualize treatment decisions and remain attentive to new safety data as longer-term evidence emerges.”
GLP-1 receptor agonists are being used by millions of people worldwide for diabetes and obesity, yet their long-term cancer safety has remained uncertain. According to Chiang, early observational studies and case reports raised concerns about potential links with certain cancers such as thyroid and pancreatic cancers. “At the same time, other observational studies have suggested a lower risk of certain cancers, particularly obesity-related cancers, with GLP-1RA use,” he said. “This mixture of signals has contributed to uncertainty in the field.”
In a systemic review and meta-analysis, Chiang and coauthors used PubMed and other online sources to pull together cancer events across 48 randomized, placebo-controlled clinical trials involving 94,245 participants to provide an assessment of cancer risk with GLP-1RAs. The researchers used the Cochrane Risk of Bias 2 tool to evaluate the risk of bias, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence, and random-effects meta-analysis to pool odds ratios (ORs).
Over a median follow-up of 70 weeks, the authors reported that trials with moderate-certainty evidence suggest GLP-1RAs “probably have little or no effect” on the risk of thyroid cancer (OR, 1.37), pancreatic cancer (OR, 0.84), breast cancer (OR, 0.95), or kidney cancer (OR, 1.12).
Meanwhile, trials with low or very low certainty evidence suggested that GLP-1RAs “may have little or no effect” on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer, as well as multiple myeloma or meningioma. The authors noted that this was likely due to sparse events, wide confidence intervals, and considerable variation across trials.
“One thing that stood out to us was how reassuringly consistent the results were across different trials and patient populations: we did not see a clear signal that GLP-1RA therapy increased overall cancer risk,” Chiang said. “Given the longstanding concerns about specific cancer types (such as thyroid and pancreatic cancer), the absence of an increased signal in those pre-specified sites was reassuring.”
At the same time, he continued, some recent observational studies have suggested a reduced risk of certain obesity-related cancers among GLP-1RA users. “This is in contrast to our study, where we showed that GLP-1RA neither increased nor decreased the risk of obesity-related cancers,” Chiang said. “This discrepancy likely reflects differences in study design, confounding structures, patient populations, and the degree of weight loss achieved in real-world settings versus clinical trials.”
He emphasized that studies with 5–10 years or more of follow-up are required to fully determine whether GLP-1RAs influence the incidence or progression of cancer, particularly site-specific and obesity-related cancers. “Trials or large observational studies with pre-specified, standardized cancer endpoints and adjudication will be key,” Chiang said. “In addition, evidence regarding the safety of GLP-1RAs in individuals with pre-existing cancer remains limited. It will be important to investigate whether GLP-1RAs affect the recurrence or progression among participants with a history of cancer.”
The researchers reported having no disclosures.
Source: Annals of Internal Medicine
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.