Efficacy and safety of polyethylene glycol loxenatide as add-on to metformin in patients with type 2 diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 3b trial.

AIM: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This was a multicentre, randomized, double-blind, placebo-controlled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 µg, and metformin + PEX168 200 µg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. RESULTS: The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (-1.16% [0.08%] and -1.14% [0.08%] with 100 and 200 µg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 µg (37.4%) and PEX168 200 µg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred. CONCLUSION: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin.

Strigolactones alleviate the toxicity of polystyrene nanoplastics (PS-NPs) in maize (Zea mays L.).

Nanoplastics are widely used across various fields, yet their uptake can potentially exert adverse effects on plant growth and development, ultimately reducing yields. While there is growing awareness of the phytotoxicity caused by nanoplastics, our understanding of effective strategies to prevent nanoplastic accumulation in plants remains limited. This study explores the role of strigolactones (SLs) in mitigating the toxicity of polystyrene nanoplastics (PS-NPs) in Zea mays L. (maize). SLs application markedly inhibited PS-NPs accumulation in maize roots, thus enhancing the root weight, shoot weight and shoot length of maize. Physiological analysis showed that SLs application activated the activities of antioxidant defence enzymes, superoxide dismutase and catalase, to decrease the malondialdehyde content and electrolyte leakage and alleviate the accumulation of H2O2 and O2.- induced by PS-NPs in maize plants. Transcriptomic analyses revealed that SLs application induced transcriptional reprogramming by regulating the expression of genes related to MAPK, plant hormones and plant-pathogen interaction signal pathways in maize treated with PS-NPs. Notably, the expression of genes, such as ZmAUX/IAA and ZmGID1, associated with phytohormones in maize treated with PS-NPs underwent significant changes. In addition, SLs induced metabolic dynamics changes related to amino acid biosynthesis, ABC transporters, cysteine and methionine metabolism in maize treated with PS-NPs. In summary, these results strongly reveal that SLs could serve as a strategy to mitigate the accumulation and alleviate the stress of PS-NPs in maize, which appears to be a potential approach for mitigating the phytotoxicity induced by PS-NPs in maize.