Yin Jingxia,Xu Xiaoli,Gui Jing,et al.Effect of sacubitril/valsartan on insulin resistance and chronic inflammation in patients with hypertension and diabetes[J].Journal of Chongqing Medical University,2026,51(4):477-485.
Yin Jingxia,Xu Xiaoli,Gui Jing,et al.Effect of sacubitril/valsartan on insulin resistance and chronic inflammation in patients with hypertension and diabetes[J].Journal of Chongqing Medical University,2026,51(4):477-485. DOI: 10.13406/j.cnki.cyxb.004030.
Effect of sacubitril/valsartan on insulin resistance and chronic inflammation in patients with hypertension and diabetes
选取2024年8月至2025年5月武警重庆总队医院门诊及住院患者120例,随机分为沙库巴曲缬沙坦组(试验组,60例)和苯磺酸氨氯地平组(对照组,60例),观察治疗12周后人体测量学指标、血压、糖脂代谢、基于C肽的稳态模型评估胰岛素抵抗指数[homeostasis model assessment of insulin resistance(C),HOMA-IR(C)]、C反应蛋白(C-reactive protein,CRP)及尿微量蛋白(microalbuminuria,MAU)等指标变化。
To investigate the effect of sacubitril/valsartan versus amlodipine besylate on insulin resistance,glucose and lipid metabolism,chronic inflammation,and early kidney injury in patients with type 2 diabetes mellitus and hypertension.
Methods
2
A total of 120 outpatients and inpatients who were treated in Chongqing Armed Police Corps Hospital from August 2024 to May 2025 were enrolled and randomly divided into sacubitril/valsartan group and amlodipine besylate group,with 60 patients in each group. The two groups were observed in terms of the changes in anthropometric parameters,blood pressure,glucose and lipid metabolism,C-peptide-based homeostasis model assessment of insulin resistance[HOMA-IR(C)],C-reactive protein(CRP),and urinary microalbumin(MAU) after 12 weeks of treatment.
Results
2
Finally 107 patients(52 in the experimental group and 55 in the control group) completed follow-up,and there were no significant differences between the two groups in the degree of reduction in blood pressure and the rate of reaching the standard(
P
>
0.05). There were also no significant differences in the degree of improvements in parameters for glucose and lipid metabolism between the two groups(
P
>
0.05). The two groups showed a sim
ilar degree of reduction in MAU(
P
>
0.05). In the sacubitril/valsartan group,overweight patients had a median reduction of 0.053(-0.006,0.096) for HOMA-IR(C) and a median reduction of 2.37(0.49,5.17) mg/L for CRP,both of which were significantly better than the values in the control group(
P
<
0.05). The partial correlation analysis showed a moderate positive correlation between ΔHOMA-IR(C) and ΔCRP(
r
=0.334,
P
=0.031),which was independent of the changes in body weight,blood pressure,and glucose and lipid metabolism.
Conclusion
2
In addition to a comparable effect to amlodipine in reducing blood pressure,sacubitril/valsartan can independently improve insulin resistance and reduce inflammation via an “insulin-inflammation axis”,especially in overweight patients,while extra early renal benefit is not observed. This study provides a new reference for selecting drugs with both antihypertensive and anti-inflammatory properties in patients with hypertension and diabetes.
Yin JX , Yu L , Pu DL , et al . Interpretation of the China guidelines for the prevention and treatment of diabetes(2024 edition) [J ] . J Chongqing Med Univ , 2025 , 50 ( 5 ): 557 - 564 .
Fang Lyu 1 , Xiaoling Cai 1,Chu Lin, et al. Cardiovascular risk profile and clinical characteristics of diabetic patients: a cross-sectional study in China[J ] . 2021, 135 ( 3 ): 295 - 300 .
Liu MB , He XY , Yang XH , et al . Interpretation of annual report on cardiovascular health and diseases in China 2024 [J ] . J Clin Cardiol , 2025 , 41 ( 7 ): 492 - 511 .
Chinese Society of Endocrinology , China Endocrine and Metabolic Disease Specialist Alliance . Consensus on clinical management of diabetes mellitus complicated with chronic kidney disease in China [J ] . Chin J Endocrinol Metab , 2024 , 40 ( 6 ): 455 - 461 .
Yuan Y , Isasi CR , Al-Rousan T , et al . Associations of concurrent hypertension and type 2 diabetes with mortality outcomes: a prospective study of U. S. adults [J ] . Diabetes Care , 2025 , 48 ( 7 ): 1241 - 1250 .
Zhang P , Mo DG , Zeng WH , et al . Association between triglyceride-glucose related indices and all-cause and cardiovascular mortality among the population with cardiovascular-kidney-metabolic syndrome stage 0-3: a cohort study [J ] . Cardiovasc Diabetol , 2025 , 24 ( 1 ): 92 .
McMurray JJV , Jackson AM , Lam CSP , et al . Effects of sacubitril-valsartan versus valsartan in women compared with men with heart failure and preserved ejection fraction: insights from PARAGON-HF [J ] . Circulation , 2020 , 141 ( 5 ): 338 - 351 .
Esser N , Barrow BM , Choung E , et al . Neprilysin inhibition in mouse islets enhances insulin secretion in a GLP-1 receptor dependent manner [J ] . Islets , 2018 , 10 ( 5 ): 175 - 180 .
Willard JR , Barrow BM , Zraika S . Improved glycaemia in high-fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels [J ] . Diabetologia , 2017 , 60 ( 4 ): 701 - 708 .
β-Cell Function Study Group of Chinese Diabetes Society , Endocrinology Branch of Jiangsu Medical Association . Clinical experts' consensus on evaluation and protection of islet β-cell function in type 2 diabetes mellitus [J ] . Chin J Diabetes Mellit , 2022 , 14 ( 6 ): 533 - 543 .
Kosovski IB , Ghiga D , Ciurea CN , et al . Evaluation of fasting glucose-insulin-C-peptide-derived metabolic indices for identifying metabolic syndrome in young,healthy adults [J ] . Nutrients , 2024 , 16 ( 13 ): 2135 .
Li X , Zhou ZG , Qi HY , et al . Evaluation of insulin resistance and islet β cell function by using fasting C peptide instead of insulin to improve Homa formula [J ] . J Cent South Univ Med Sci , 2004 , 29 ( 4 ): 419 - 423 .
Thakur S , Mohanty P , Jadhav MS , et al . A perspective on the development of small molecular neprilysin inhibitors (NEPi) with emphasis on cardiorenal disease [J ] . Eur J Med Chem , 2024 , 280 : 116932 .
Sankhe R , Pai SRK , Kishore A . Tumour suppression through modulation of neprilysin signaling: A comprehensive review [J ] . Eur J Pharmacol , 2021 , 891 : 173727 .
Chrysant SG . Pharmacokinetic,pharmacodynamic,and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan [J ] . J Am Soc Hypertens , 2017 , 11 ( 7 ): 461 - 468 .
Kittelson KS , Junior AG , Fillmore N , et al . Cardiovascular-kidney-metabolic syndrome—An integrative review [J ] . Prog Cardiovasc Dis , 2024 , 87 : 26 - 36 .
Ruilope LM , Dukat A , Böhm M , et al . Blood-pressure reduction with LCZ696,a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised,double-blind,placebo-controlled,active comparator study [J ] . Lancet , 2010 , 375 ( 9722 ): 1255 - 1266 .
Yu SJ , Liu DH , Song ZM , et al . Change of plasma level of soluble NRP-1 and SOD in hypertensive patients and hypertensive diabetic patients [J ] . J Sun Yat-sen Univ(Med Sci) , 2021 , 42 ( 1 ): 81 - 86 .
Jordan J , Stinkens R , Jax T , et al . Improved insulin sensitivity with angiotensin receptor neprilysin inhibition in individuals with obesity and hypertension [J ] . Clin Pharmacol Ther , 2017 , 101 ( 2 ): 254 - 263 .
Sun M , Zhong Y , Yang HJ , et al . Research progress on the anti-glycolipid metabolism disorder effects of catalpol and its mechanism [J ] . J Chongqing Med Univ , 2025 , 50 ( 7 ): 849 - 859 .
Hogan AE , Davis C , Jenkins BJ , et al . Repurposing metabolic drugs as anti-inflammatory agents [J ] . Trends Endocrinol Metab , 2025 : S1043-S2760(25)00149 - 3 .
Ayza MA , Zewdie KA , Tesfaye BA , et al . Anti-diabetic effect of telmisartan through its partial PPARγ-agonistic activity [J ] . Diabetes Metab Syndr Obes , 2020 , 13 : 3627 - 3635 .
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