Context Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the liraglutide development program, a glucagon-like peptide-1 receptor agonist (GLP-1RA), subjects treated with the active drug had a higher absolute number of breast cancer events. Objective To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Data sources We searched MEDLINE, Embase, Web of Science, and CENTRAL from inception to February 8, 2020. Study Selection Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. Data extraction Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. Data synthesis We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48267 subjects treated with GLP-1RAs, 130 developed breast cancer compared to 107 of 40755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76 to 1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48 to 2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusions Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.

Background: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the liraglutide development program, a glucagon-like peptide-1 receptor agonist (GLP-1RA), subjects treated with the active drug had a higher absolute number of breast cancer events. Aim: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Methods: We searched MEDLINE, Embase, Web of Science, and CENTRAL from inception to February 8, 2020. Three pairs of reviewers examined and retrieved abstractsand full-text articles for RCTs of GLP-1RAs versus non-GLP-1RA controls(active or placebo) in adults with overweight, obesity, prediabetes, or diabetes,with a minimum follow-up period of 24 weeks and which reported at least oneevent of breast cancer or benign breast neoplasm. Divergences were dealt withby consensus. Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. This study follows PRISMA reporting guidelines. Results: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48267 subjects treated with GLP-1RAs, 130 developed breast cancer compared to 107 of 40755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76 to 1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48 to 2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusion: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms. Register: This systematic review was preregistered in PROSPERO (CRD42019132704).

Summary The US Food and Drug Administration (FDA) reported in February 2020 an increased risk of cancer with lorcaserin in the follow‐up of the CAMELLIA‐TIMI 61 trial. This systematic review and meta‐analysis addresses whether lorcaserin is associated with higher incidence of cancer compared with other interventions or no treatment. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials that compared lorcaserin with other interventions or no treatment in adults. We performed descriptive synthesis of all included studies and conducted meta‐analysis of trials that reported new cases of cancer. From 11 trials, comprising 21,299 individuals, four studies were included in the meta‐analysis and reported 476 cases of cancer in 10,342 subjects in the lorcaserin group and 438 among 9429 individuals randomized to placebo (relative risk [RR]: 1.08; 95% confidence interval [95% CI]: 0.96–1.23). The result was heavily influenced by the CAMELLIA‐TIMI 61 trial. In this study, the lorcaserin group had a higher risk of lung and pancreatic but not colon cancer. Overall risk of bias was low, and quality of evidence was moderate. The current evidence does not confirm the increased risk of cancer with lorcaserin but suggests a trend in this direction, with a greater incidence of some subtypes such as lung and pancreas.

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Background People with type 2 diabetes (T2D) have higher risks of cancer incidence and death. We aimed to evaluate the relationship between dietary and physical activity-based lifestyle intervention and cancer outcomes among prediabetes and T2D populations. Methods We searched for randomized control trials with at least 24 months of lifestyle interventions in prediabetes or T2D populations. Data was extracted by pairs of reviewers and discrepancies were resolved by consensus. Descriptive syntheses were performed, and the risk of bias was assessed. Relative risks (RRs) and 95% confidence intervals (CI) were estimated using a pairwise meta-analysis with both random effects model and general linear mixed model (GLMM). Certainty of evidence was evaluated using the GRADE framework and trial sequential analysis (TSA) was conducted to assess if current information is enough for definitive conclusions. Subgroup analysis was performed by glycemic status. Results Six clinical trials were included. Among 12,841 participants, the combined RR for cancer mortality comparing lifestyle interventions with usual care was 0.94 (95% CI 0.81 to 1.10 using GLMM and 0.82 to 1.09 using random effects model). Most studies had a low risk of bias, and the certainty of evidence was moderate. TSA showed that cumulative Z-curve reached futility boundary while total number did not reach detection boundary. Conclusion Based on the limited data available, dietary and physical activity-based lifestyle interventions had no superiority to usual care on reducing cancer risk in populations with pre-diabetes and T2D. Lifestyle interventions focused on cancer outcomes should be tested to better explore their effects.

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