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Nowadays, the incidence of diabetes is increasing year by year, and the use of hypoglycemic drugs is also increasing. At the same time, everyone is paying more and more attention to blood pressure, blood sugar, and blood lipids. If you can “by the way” reduce blood pressure and lipids while taking hypoglycemic drugs, wouldn’t it be “the best of both worlds and serve multiple purposes with one stone”?
Today, we will sort out one of the “sidelines” of some hypoglycemic drugs—the antihypertensive effect for your reference.
Said the previous words: First, “side business” cannot replace “main business”; second, domestic clinical drug use mainly refers to domestic guidelines/consensus and related drug instructions.
01
Biguanide
Metformin: Currently the first-line hypoglycemic drug, in terms of antihypertensive effect, metformin has no effect on normal blood pressure, but on abnormal glucose metabolism and 2 Type 2 diabetes (T2DM)pregnancy with elevated blood pressure has antihypertensive effect[1-3]. Works equally well on pure systolic, diastolic, or both.
This antihypertensive effect may be related to its inhibition of asymmetric dimethylarginine (ADMA) activity, increase of nitric oxide (NO) levels, and restoration of ADMA-NO balance in the body[4] . Other studies suggest that metformin can also reduce blood pressure by improving insulin resistance and reducing vascular smooth muscle pressure [5-6].
02
Alpha-glucosidase inhibitor
Acarbose: As a commonly used hypoglycemic drug, acarbose also improves blood pressure in T2DM patients. Blood pressure, diastolic blood pressure, and mean blood pressure were all lower than those in the placebo-treated group. On the other hand, it also has a certain antihypertensive effect on patients with coronary heart disease with impaired fasting glucose (IGT), but its specific mechanism remains to be further studied[7].
03
Thiazolidinediones
Pioglitazone: T2DM patients are often accompanied by refractory increased blood pressure clinically, mainly due to hyperglycemia and interleukin and other inflammatory factors stimulate blood vessels to cause vasoconstriction and vasoconstriction Wall thickening results in [8].
As an insulin sensitizer, itimproves insulin sensitivity by increasing the sensitivity of fat, muscle and other peripheral tissues to insulin, promoting its uptake and utilization of glucose, reducing plasma insulin levels, and improving insulin resistance, so as to achieve the purpose of lowering blood pressure[9]. Another study suggests that pioglitazone can reduce blood pressure by inhibiting the vasoconstrictor function of angiotensin II and promoting NO synthesis [10,11].
04
Sodium-glucose co-transporter-2 (SGLT-2) inhibitor
SGLT-2 inhibitors also have the effect of regulating blood pressure. At present, it is believed that the antihypertensive effect of SGLT-2 inhibitors is mainly related to SGLT-2 inhibitors increasing urinary sodium excretion, reducing body weight, thereby reducing cardiac afterload and inhibiting the sympathetic nervous system (SNS).
Because SGLT-2 inhibitors also inhibit the reabsorption of sodium ions in the process of reducing glucose reabsorption, thus reducing the blood volume of patients through natriuresis and diuresis, which can significantly reduce Blood pressure in patients with volume-dependent hypertension.
However, there is no report on the persistent urinary sodium loss caused by SGLT-2 inhibitors, which may be related to the rapid compensation of the body’s urinary sodium.
1. Dapagliflozin: Dapagliflozin monotherapy or combination therapy, the systolic blood pressure and diastolic blood pressure of the patients were significantly lower than those before treatment, with obvious Antihypertensive effect [12-13].
2. Canagliflozin: Except for single drug, concomitant use of antihypertensive drugs did not significantly affect the blood pressure-lowering effect of canagliflozin[14 -15].
3. Empagliflozin: It reduces blood pressure without increasing heart rate, but it has no synergistic antihypertensive effect when used in combination with other antihypertensive drugs. The mechanism of action remains to be further studied [16-18].
05
Glucagon-like peptide-1 receptor agonist (GLP-1RA)
GLP-1RA has blood pressure lowering effects, mainly lowering systolic blood pressure [19-22]. Among them, liraglutide may reduce blood pressure by reducing body weight, increasing urinary sodium excretion, reducing free fatty acid (FFA), and improving endothelial function; in addition, it can also treat preeclampsia in hypertensive diseases of pregnancy. In murine models, it can reduce blood pressure, improve renal function and upregulate endothelial nitric oxide synthase (NOS3) expression [23,24].
06
DPP-4 inhibitors
DPP-4 inhibitors improve blood pressure in hypertensive patients by suppressing inflammatory responses and reducing oxidative stressTube endothelial function. In addition, it can also regulate blood pressure by activating the sympathetic nervous system, interfering with the renin-angiotensin-aldosterone system (RAAS), regulating Na/H2O metabolism, and reducing insulin resistance (IR) [25].
Sitagliptin: It can more effectively reduce blood pressure in patients with diabetes and hypertension, improve vascular endothelial function and oxidative stress response, and improve the freedom from cardiovascular events patient survival [25,27].
Table 1: Effects of commonly used hypoglycemic drugs on blood pressure
References:
[1] He Bingxian. A modern perspective on the application of metformin in the prevention and treatment of hypertension [J]. Chinese Journal of Hypertension, 2018,26(06):508-509.
[2]Racine Jenna L, Adams Jacquelyn H, Antony Kathleen M, el. Metformin Exposure and Risk of Hypertensive Disorders of Pregnancy in Patients with Type 2 Diabetes. [J]. American journal of perinatology, 2021, 38(11).
[3]Ouyang Hong,AlMureish Abdulrahman,Wu Na.Research progress of metformin in gestational diabetes mellitus:a narrative review.[J].Annals of palliative medicine,2021,10(3) .
[4] Yang Zhousheng, Chen Xiaoyu. Research progress on the multipotent pharmacological effects of metformin [J]. China New Clinical Medicine, 2021, 14(04): 422-426.
[5] Xu Guiyan, Ying Xiaolei, Cao Haihui. Clinical effect of metformin in the treatment of hypertension complicated with metabolic syndrome [J]. General Medicine Clinic and Education, 2017, 15(01): 89-91.
[6] Su Xin, Hu Rong. Discussion on blood pressure control of hypertension complicated with diabetes mellitus [J]. Chongqing Medicine, 2018, 47(16): 2219-2222.
[7] Liu Sixu, Yu Shengqin, Zhang Shuying. Research progress on the cardiovascular benefit mechanism and safety of acarbose [J]. Journal of Practical Cardiovascular and Cerebrovascular Diseases, 2019 ,27(11):102-106.
[8] Zhou Heming, Zhou Yanping. Feasibility of adjuvant pioglitazone in the treatment of elderly patients with type 2 diabetes and hypertension [J]. Journal of Chronic Diseases, 2019,20(09):1384-1385+1388 .
[9] Zang Yongjun, Long Mengmeng, Liu Dong, et al. Research progress of pioglitazone in the treatment of type 2 diabetes [J]. Chinese Medicine Guide, 2017, 15(36): 4-5 .
[10] Zhang Xiulong, Zhan Changhe. Clinical efficacy of pioglitazone combined with acarbose in the treatment of elderly patients with type 2 diabetes and hypertension [J]. Journal of Clinical Rational Medicine, 2019, 12(09) :11-12+14.
[11]Kvandova M, Barancik M, Balis P, Puzserova A, Majzunova M, Dovinova I. The peroxisome proliferator-activated receptor gamma agonist pioglitazone improves nitric oxide availability, renin-angiotensin system and aberrant redox regulation in the kidney of pre-hypertensive rats.[J].Journal of physiology and pharmacology:an official journal of the Polish Physiological Society,2018,69(2).
[12] Guo Caihong, Gao Xiuying. The effect of dapagliflozin on metabolic indicators in patients with type 2 diabetes mellitus with metabolic syndrome [J]. Journal of Clinical Military Medicine, 2018, 46(05): 585- 587.
[13] Hao Yanhong, Wu Qing, Li Yun, et al. Clinical application of dapagliflozin in patients with type 2 diabetes mellitus complicated with hypertension [J]. Chinese Contemporary Medicine, 2021, 28 (18):12-16.
[14] Wang Fei, Lu Xinzheng. Research progress of canagliflozin on cardiovascular protection in patients with type 2 diabetes [J]. Advances in Cardiovascular Diseases, 2020, 41(03) :231-234.
[15] Chen Tianyu, Chen Qiying, Zhang Yuezhen. Meta-analysis of the effects of canagliflozin on cardiovascular factors in patients with type 2 diabetes [J]. Journal of Pharmacoepidemiology, 2021, 30(04 ):239-244+288.
[16] Kario Kazuomi, Okada Kenta, Kato Mitsutoshi, Nishizawa Masafumi, Yoshida Tetsuro, Asano Tsuguyoshi, Uchiyama Kazuaki, Niijima Yawara, Katsuya Tomohiro, Urata Hidenori, Osuga Jun-Ichi, Fujiwara Takeshi ,Yamazaki Shoji,Tomitani Naoko,Kanegae Hiroshi.24-Hour Blood Pressure-LoweRing Effect of an SGLT-2 Inhibitor in Patients with Diabetes and Uncontrolled Nocturnal Hypertension: Results from the Randomized,Placebo-Controlled SACRA Study.[J].Circulation,2018,139(18).
[17] Zhou Pei, Tang Xiangyu, Deng Yunxia, et al. Research progress on the cardiovascular protective effect and mechanism of SGLT-2 inhibitor – empagliflozin [J]. Chinese Medicine Guide Journal, 2021, 23(11):823-827.
[18] Sun Yong, Tian Lin, Wu Rangbing, et al. Research status of new drug empagliflozin for the treatment of type 2 diabetes [J]. Chinese Journal of Diabetes, 2018, 26(06): 523-528.
[19]Dilip Sharma,Suril Verma,Shivani Vaidya,el.Recent updates on GLP-1 agonists:Current advancements&challenges[J].Biomedicine&Pharmacotherapy,2018,108.
[20] Zhao Yanzhen, Du Jing. Research progress of GLP-1 receptor agonists in the treatment of type 2 diabetes [J]. Gerontology Research, 2021, 2(03): 55-60 .
[21] Chen Ya, Wang Yanping, Zhang Liang, et al. Effects of liraglutide on blood glucose, blood lipids, blood pressure and carotid plaque in patients with type 2 diabetes mellitus complicated with atherosclerosis[21] J]. Journal of Hainan Medical College, 2019, 25(10): 730-734.
[22] Xu Qinghai, Ma Ying, Wu Yanchun, et al. Effects of liraglutide on blood sugar, blood pressure and blood lipids in patients with type 2 diabetes and hypertension [J]. Shandong Medicine, 2017, 57(21):77-79.
[23]Younes Subhi Talal,Maeda Kenji J,Sasser Jennifer,el.The glucagon-like peptide 1 receptor agonist liraglutide attenuates placental ischemia-induced hypertension.[J].American journal of physiology .Heart and circulatory physiology,2020,318(1).
[24] Zhang Xuehui, Li Juan. Research progress on the mechanism of antihypertensive effect of liraglutide [J]. Clinical Medical Research and Practice, 2021,6(08):196-198.
[25] Zhang Jianqiang, Chen Qiuyue, Zhong Jixin, Liu Chaohong, Zheng Bing, Gong Quan. DPP-4 Inhibitors as Potential Candidates for Antihypertensive Therapy: Improving Vascular Inflammation and Assisting the Action of Traditional Antihypertensive Drugs.[J].Frontiers in immunology,2019,10.
[26] Du Yingxuan, Wang Hui. Effects of sitagliptin on blood pressure, arterial stiffness and endothelial function in diabetic patients with hypertension [J]. Guangxi Medicine, 2020, 42 (10):1193-1197.
[27] Chen N. Effects of sitagliptin adjuvant therapy on diabetes and hypertension on glucose and lipid metabolism and vascular endothelial function in patients [J]. Diabetes New World, 2020, 23(24 ):91-93+102.
This article was first published: Medical Endocrinology Channel
The author of this article: Yu Yijiang, Department of Endocrinology, Huaian Hospital of Traditional Chinese Medicine
Editor in charge: Yuan Xueqing, Zhang Li
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