Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Location VUmc, Amsterdam, The Netherlands.
Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Location VUmc, Amsterdam, The Netherlands.
Diabetes Metab. 2021 Sep;47(5):101223. doi: 10.1016/j.diabet.2021.101223. Epub 2021 Jan 8.
Preclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D).
A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m, HbA 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma.
Liraglutide decreased HbA by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters.
These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236).
临床前数据表明，胰高血糖素样肽（GLP）-1 受体激动剂或二肽基肽酶（DPP）-4 抑制剂的治疗可能会改变肠道微生物组，从而有助于其有益的（心脏代谢）作用。因此，我们的研究旨在调查这些药物对 2 型糖尿病（T2D）成人肠道微生物组组成的影响。
共纳入 51 名接受二甲双胍和/或磺脲类药物治疗的 T2D 成人（平均年龄±标准差：62.8±6.9 岁，BMI 31.8±4.1kg/m，HbA 7.3±0.6%），进行为期 12 周的随机、双盲试验。患者每天一次接受 GLP-1 受体激动剂利拉鲁肽（1.8mg sc）或 DPP-4 抑制剂西他列汀（100mg）或匹配的安慰剂治疗 12 周。在干预开始后的基线和 12 周收集粪便样本。通过 16S rRNA 基因测序分析进行微生物组分析。在粪便和血浆中测量胆汁酸。
利拉鲁肽使 HbA 降低 1.3%（95%CI：-1.7 至-0.9），并倾向于降低体重（-1.7kg，95%CI：-3.6 至 0.3），但增加了粪便次级胆汁酸脱氧胆酸。西他列汀使 HbA 降低 0.8%（95%CI：-1.4 至-0.4），而体重保持稳定（-0.8kg，95%CI：-2.7 至 1.0），但增加了粪便中胆酸、鹅去氧胆酸和熊去氧胆酸的水平。然而，利拉鲁肽和西他列汀均未影响肠道微生物组的 alpha 多样性或 beta 多样性，也未发现微生物组成的变化与临床参数相关。
当作为二甲双胍或磺脲类药物的附加治疗时，利拉鲁肽和西他列汀对葡萄糖代谢、体重和胆汁酸的有益作用与肠道微生物组的变化无关（NCT01744236）。
