Aim: To conduct a meta‐analysis of randomized clinical trials (RCTs) to investigate whether there is an association between glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment and thyroid cancer. Materials and Methods: In this meta‐analysis of RCTs, we included studies comparing a GLP‐1RA with any comparator, lasting at least 52 weeks, and reporting the incidence of adverse events independently of the principal endpoint and population. All cases of thyroid cancer were collected. Results: We retrieved 64 trials, 26 of which reported at least one incident case of thyroid cancer. GLP‐1RA treatment was associated with a significant increase in the risk of overall thyroid cancer (Mantel‐Haenzel odds ratio [MH‐OR] 1.52 [95% confidence interval {CI} 1.01, 2.29]; P = 0.04, I ² = 0%), with a fragility index of 1, and a 5‐year number needed to harm of 1349. The association remained significant when including only trials lasting at least 104 weeks (MH‐OR 1.76 [95% CI 1.00, 3.12]; P = 0.05). No significant association was found for papillary thyroid cancer (MH‐OR 1.54 [95% CI 0.77, 3.06]; P = 0.22) or medullary thyroid cancer (MH‐OR 1.44 [95% CI 0.23, 9.16]; P = 0.55). Conclusions: Our meta‐analysis showed that GLP‐1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.

Aims: To assess if there is a difference in the oncogenic risk between GLP‐1 RA and comparators in randomized controlled trials. Materials and Methods: A meta‐analysis of randomized controlled trials comparing GLP‐1RA to any comparators for diabetes and/or obesity, lasting at least 52 weeks. The endpoints included the incidence of overall cancers and single malignancies. Results: Fifty trials were included. GLP‐1RA treatment was not associated with a significant difference in risk for overall cancer (MH‐OR 1.05, 95% confidence interval [CI] [0.98, 1.13]). Uterine cancer was significantly reduced in the GLP‐1RA arm in trials performed in subjects with obesity (MH‐OR 0.24, 95% CI [0.06, 0.94]), but not in those aimed at diabetes treatment (MH‐OR 0.92, [0.58, 1.47]). We detected an increase in the risk for thyroid cancer (MH‐OR 1.55, [1.05, 2.27]), more evident in longer‐term trials, and in the risk for colorectal cancer (MH‐OR 1.27 [1.03, 1.57]), which, conversely, was significant only in shorter‐term trials. No significant difference in the risk was detected for any other cancer. Conclusions: GLP‐1 RA do not appear to produce an effect on most malignancies in clinical trials. A reduction of very close obesity‐associated cancers seems possible, whereas a risk signal for thyroid cancer was observed, prompting the need for further specific studies. On the other hand, the small increase observed in colorectal cancer in shorter‐term trials may be the effect of a disproportionate increase in diagnostic procedures in the GLP‐1 RA arm, because of the suspicion raised by common side effects of GLP‐1 RA.

In order to better define the need for influenza vaccination in people with diabetes (DM), we collected all available evidence on the effect of DM as a risk factor for complications of both seasonal and pandemic influenza, and on the specific effectiveness of vaccines in patients with DM. Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and Embase databases were performed, one for each metanalysis, collecting all observational studies and randomized clinical trials performed on humans up to May 31st, 2022. We retrieved 34 observational studies comparing risk for influenza complications in people with or without diabetes, and 13 observational studies assessing vaccine effectiveness on preventing such complications. Mortality for influenza and hospitalization for influenza and pneumonia resulted significantly higher in individuals with versus without DM, both when unadjusted and adjusted data are analyzed. In diabetic individuals vaccinated for influenza overall hospitalization, hospitalization for influenza or pneumonia and overall mortality are significantly lower in comparison with not vaccinated DM subjects, both when unadjusted and adjusted data were analyzed. This systematic review and meta-analysis shows that: 1) influenza is associated with more severe complications in diabetic versus not diabetic individuals and 2) influenza vaccination is effective in preventing clinically relevant outcomes in adults with DM with a NNT (number needed to treat) of 60, 319, and 250 for all-cause hospitalization, specific hospitalization, and all-cause mortality, respectively. The identification of diabetic patients as the target of vaccination campaigns for influenza appears to be justified by available clinical evidence.