Glucagon-like peptide-1 receptor agonist (GLP-1RAs) labels warn about acute pancreatitis (AP) and impose upon doctors the obligation to inform patients about symptoms of AP. Here we systematically reviewed the risk of AP in randomized placebo-controlled trials (RCTs) investigating the effect of GLP-1RAs in type 2 diabetes. We performed a systematic review with meta-analysis of long-term (minimum 24 months), placebo-controlled GLP-1RA RCTs in which AP was a predefined adverse event and adjudicated by blinded and independent adjudicating committees. Three high-quality RCTs included a total of 9347 GLP-1RA-treated and 9353 placebo-treated patients with type 2 diabetes. Compared to placebo, treatment with GLP1-RA was not associated with increased risk of AP (Peto odds ratio 0.745 [95% CI, 0.47-1.17]). Trial Sequential Analysis suggested that additional evidence is needed. In conclusion, this review found no evidence that treatment with GLP-1RA increases the risk of AP in patients with type 2 diabetes.

Objective: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake. Design: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, doubleblinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 mg (nZ124), 200 mg (nZ122), or 300 mg (nZ119) selenium-enriched yeast or matching yeast-based placebo tablets (nZ126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period. Methods: Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT 3 ), and free thyroxine (FT 4 ) at baseline, and after 6 months, and 5 years of supplementation. Results: Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P!0.001). Serum TSH and FT 4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (PZ0.010) and 0.11 pmol/l (PZ0.015), respectively, per 100 mg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT 3 and FT 3 :FT 4 ratio. Conclusions: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT 4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved.

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