目的 评估钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)对2型糖尿病(T2DM)合并高血压(HBP)患者的疗效及安全性。方法 通过 PubMed、Embase、 Cochrane Library 、Web of science、知网、万方、维普数据库,查找截至 2025-04-30发表的相关SGLT2i治疗T2DM合并高血压患者的随机对照试验(RCT)。由2名研究员通过纳入和排除标准分别进行文献筛选、信息提取和文献质量评价,应用RevMan 5.3软件进行数据分析。主要结局指标为 24 h动态收缩压(SBP)、24 h动态舒张压(DBP)、坐位SBP、坐位DBP及不良反应如低血糖、尿路感染、生殖器感染和低容量血症等。结果 共纳入10项随机对照试验。结果显示,与安慰剂组相比,SGLT2i组可显著降低24 h动态收缩压(WMD =-4.78,95% CI:-6.31~-3.25,P＜0.00001)及24 h动态舒张压(WMD =-2.57,95% CI:-3.85~-1.29,P＜0.000 01)。然而,在两项分析中均观察到较高的异质性水平(SBP:I2=85%;DBP:I2=94%)。排除特定研究的敏感性分析降低了异质性后,血压仍显著降低且具有统计学意义(P＜0.000 01)。同时,与安慰剂组相比,SGLT2i 组可显著降低T2DM合并高血压患者的坐位 SBP 水平(WMD =-4.98,95% CI:-6.64~-3.32,P＜0.000 01)。此外,SGLT2i联合常规降压方案与低血糖症(RR=1.85,95%CI:1.09~ 3.13,P＜0.05)、生殖器感染(RR=2.48,95%CI:1.26~ 4.87,P＜0.05)的风险增加相关;在低容量血症(RR=1.85,95%CI:0.51~ 6.74,P＞0.05)及尿路感染(RR=1.74,95%CI:0.9~3.39,P＞0.05)的发生率方面与常规降压联合安慰剂方案相比差异不具统计学意义。结论 SGLT2i可降低 T2DM 合并高血压患者的24小时动态血压,收缩压更显著,但需注意低血糖症和生殖器感染风险。对于患有高血压和T2DM的患者,SGLT2i 可作为标准治疗之外的有效降压治疗选择。
Abstract
Objective To evaluate the efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and hypertension(HBP). Methods Randomized controlled trials(RCTs) of SGLT-2 inhibitors in the treatment of patients with type 2 diabetes mellitus complicated with hypertension published up to April 30, 2025 were searched through PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Document screening, information extraction and literature quality evaluation were respectively done by two researchers through inclusion and exclusion criteria, and RevMan 5.3 software for data analysis. The primary outcome indicators were 24-hour ambulatory systolic blood pressure(SBP), 24-hour ambulatory diastolic blood pressure(DBP), office-seated SBP, office-seated DBP, and adverse reactions such as hypoglycaemia, urinary tract infection, genital infection, and hypovolaemia. Results A total of 10 RCTs were included. The results showed that compared with placebo group,the SGLT2i group significantly reduced 24-hour ambulatory systolic blood pressure (WMD=-4.78,95% CI:-6.31~-3.25,P＜0.000 01) and 24-hour ambulatory diastolic blood pressure (WMD=-2.57,95% CI:-3.85~-1.29,P＜0.000 01). However, high levels of heterogeneity were observed in both analyses (SBP, I2=85%; DBP, I2=94%). Sensitivity analyses after excluding specific studies reduced heterogeneity, but still had a statistically significant reduction in blood pressure(P＜0.000 01). At the same time, office-seated SBP levels in patients with T2DM and hypertension were significantly reduced in the SGLT2i group compared with placebo group(WMD=-4.98,95% CI:-6.64~-3.32,P＜0.000 01). In addition, SGLT-2 inhibitors in combination with conventional antihypertensive regimens were associated with an increased risk of hypoglycaemia (RR=1.85,95%CI:1.09~3.13,P＜0.05) and genital infections (RR=2.48,95%CI:1.26~4.87,P＜0.05); there was no statistically significant difference in the incidence of hypovolaemia (RR=1.85,95%CI:1.09~3.13,P＜0.05) and urinary tract infection (RR=1.74,95%CI:0.9~3.39,P＞0.05) compared with conventional antihypertensive combined with placebo. Conclusions SGLT2i can reduce 24-hour ambulatory blood pressure and more significant systolic blood pressure in patients with T2DM and HBP, with more significant reduction in systolic blood pressure, but it is necessary to pay attention to the risk of hypoglycaemia and genital infection. For patients with hypertension and type 2 diabetes, SGLT2i can be an effective antihypertensive treatment option in addition to standard therapy.
关键词
钠葡萄糖协同转运蛋白2抑制剂 /
高血压 /
2型糖尿病 /
安全性 /
有效性
Key words
sodium-glucose cotransporter 2 inhibitor /
hypertension /
type 2 diabetes mellitus /
safety /
efficacy
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参考文献
[1] Ogurtsova K, Guariguata L, Barengo N C, et al. IDF diabetes atlas: global estimates of undiagnosed diabetes in adults for 2021[J]. Diabetes Res Clin Pract, 2022, 183: 109118.
[2] Kolb H, Martin S. Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes[J]. BMC Med, 2017, 15(1): 131.
[3] Magliano D J, Islam R M, Barr E L M, et al. Trends in incidence of total or type 2 diabetes: systematic review[J]. BMJ, 2019, 366: l5003.
[4] Kumar V, Agarwal S, Saboo B, et al. RSSDI Guidelines for the management of hypertension in patients with diabetes mellitus[J]. Int J Diabetes Dev Ctries, 2022, 42(4): 576-605.
[5] Petrie J R, Guzik T J, Touyz R M. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms[J]. Can J Cardiol, 2018, 34(5): 575-584.
[6] Jia G, Sowers J R. Hypertension in diabetes: an update of basic mechanisms and clinical disease[J]. Hypertension, 2021, 78(5): 1197-1205.
[7] Perkovic V, Jardine M J, Neal B, et al. Canagliflozin and renaloutcomes in type 2 diabetes and nephropathy[J]. N Engl J Med, 2019, 380(24): 2295-2306.
[8] Wright E M. SGLT2 inhibitors: physiology and pharmacology[J]. Kidney360, 2021, 2(12): 2027-2037.
[9] Chen X, Hocher C F, Shen L, et al. Reno- and cardioprotective molecular mechanisms of SGLT2 inhibitors beyond glycemic control: from bedside to bench[J]. Am J Physiol Cell Physiol, 2023, 325(3): C661-C681.
[10] Lasserson T J, Thomas J, Higgins J P T. Starting a review[M/OL]//Higgins JPT, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions(v6.3). Cochrane, 2022. http://www.training.cochrane.org/handbook.
[11] Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension[J]. Diabetes Care, 2015, 38(3): 420-428.
[12] Weber M A, Mansfield T A, Cain V A, et al. Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised, double-blind, placebo-controlled, phase 3 study[J]. Lancet Diabetes Endocrinol, 2016, 4(3): 211-220.
[13] Townsend R R, Machin I, Ren J, et al. Reductions in mean 24-hour ambulatory blood pressure after 6-week treatment with canagliflozin in patients with type 2 diabetes mellitus and hypertension[J]. J Clin Hypertens(Greenwich), 2016, 18(1): 43-52.
[14] Cheng L, Fu Q, Zhou L, et al. Effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and its possible mechanisms[J]. Sci Rep, 2022, 12(1): 3525.
[15] Weber M A, Mansfield T A, Alessi F, et al. Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade[J]. Blood Press, 2016, 25(2): 93-103.
[16] Amin N B, Wang X, Mitchell J R, et al. Blood pressure-lowering effect of the sodium glucose co-transporter-2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension[J]. Diabetes Obes Metab, 2015, 17(8): 805-808.
[17] Kario K, Okada K, Kato M, et al. Twenty-four-hour blood pressure-lowering effect of a sodium-glucose cotransporter 2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension: results from the randomized, Placebo-Controlled SACRA Study[J]. Circulation, 2019, 139(18): 2089-2097.
[18] Papadopoulou E, Theodorakopoulou M P, Loutradis C, et al. Dapagliflozin does not affect short-term blood pressure variability in patients with type 2 diabetes mellitus[J]. Am J Hypertens, 2021, 34(4): 404-413.
[19] Lambers Heerspink H J, Zeeuw D, Wie L, et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes[J]. Diabetes Obes Metab, 2013, 15(9): 853-862.
[20] Ferdinand K C, Izzo J L, Lee J, et al. Antihyperglycemic and blood pressure effects of empagliflozin in black patients with type 2 diabetes mellitus and hypertension[J]. Circulation, 2019, 139(18): 2098-2109.
[21] Cherney D Z, Perkins B A, Soleymanlou N, et al. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus[J]. Cardiovasc Diabetol, 2014, 13: 28.
[22] Mone P, Varzideh F, Jankauskas S S, et al. SGLT2 inhibition via empagliflozin improves endothelial function and reduces mitochondrial oxidative stress: insights from frail hypertensive and diabetic patients[J]. Hypertension, 2022, 79(8): 1633-1643.
[23] Tada A, Burkhoff D, Naser J A, et al. Dapagliflozin enhances arterial and venous compliance during exercise in heart failure with preserved ejection fraction: insights from the CAMEO-DAPA trial[J]. Circulation, 2024, 150(13): 997-1009.
[24] Chang G J, Chen W J, Hsu Y J, et al. Empagliflozin attenuates neointima formation after arterial injury and inhibits smooth muscle cell proliferation and migration by suppressing platelet-derived growth factor-related signaling[J]. J Am Heart Assoc, 2024, 13(22): e035044.
[25] Cherney D Z, Perkins B A, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus[J]. Circulation, 2014, 129(5): 587-597.
[26] Thomson S C, Vallon V. Effects of SGLT2 inhibitor and dietary NaCl on glomerular hemodynamics assessed by micropuncture in diabetic rats[J]. Am J Physiol Renal Physiol, 2021, 320(5): F761-f771.
[27] Lundkvist P, Pereira M J, Katsogiannos P, et al. Dapagliflozin once daily plus exenatide once weekly in obese adults without diabetes: sustained reductions in body weight, glycaemia and blood pressure over 1 year[J]. Diabetes Obes Metab, 2017, 19(9): 1276-1288.
[28] Billing A M, Kim Y C, Gullaksen S, et al. Metabolic communication by SGLT2 Inhibition[J]. Circulation, 2024, 149(11): 860-884.
[29] Mayne K J, Sardell R J, Staplin N, et al. Empagliflozin lowers serum uric acid in chronic kidney disease: exploratory analyses from the EMPA-KIDNEY trial[J]. Nephrol Dial Transplant, 2025, 40(4): 720-730.
[30] Mudaliar S, Alloju S, Henry R R. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME study? a unifying hypothesis[J]. Diabetes Care, 2016, 39(7): 1115-1122.
[31] Muskiet M H A, Heerspink H J L, van Raalte D H. SGLT2 inhibitors: expanding their Empire beyond diabetes[J]. Lancet Diabetes Endocrinol, 2021, 9(2): 59-61.
[32] Verma S, Mudaliar S, Greasley P J. Potential underlying mechanisms explaining the cardiorenal benefits of sodium-glucose cotransporter 2 inhibitors[J]. Adv Ther, 2024, 41(1): 92-112.
[33] Pabel S, Wagner S, Bollenberg H, et al. Empagliflozin directly improves diastolic function in human heart failure[J]. Eur J Heart Fail, 2018, 20(12): 1690-1700.
[34] Yurista S R, Silljé H H W, Oberdorf-Maass S U, et al. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction[J]. Eur J Heart Fail, 2019, 21(7): 862-873.
[35] Lahnwong C, Palee S, Apaijai N, et al. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury[J]. Cardiovasc Diabetol, 2020, 19(1): 91.
[36] Wheeler D C, Stefánsson B V, Jongs N, et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial[J]. Lancet Diabetes Endocrinol, 2021, 9(1): 22-31.
[37] Hlyan N P, Arif T, Jaufar S S, et al. From sugar spikes to pressure peaks: navigating the world of diabetes, hypertension,obesity, and kidney health[J]. Cureus, 2024, 16(3): e57241.
[38] Wanner C, Iliev H, Duarte N, et al. Safety of empagliflozin: an individual participant-level data meta-analysis from four large trials[J]. Adv Ther, 2024, 41(7): 2826-2844.
[39] Morace C, Lorello G, Bellone F, et al. Ketoacidosis and SGLT2 inhibitors: a narrative review[J]. Metabolites, 2024, 14(5):264..
[40] Tang H, Xu C, Zhang P, et al. A profile of SGLT-2 inhibitors in hyponatremia: the evidence to date[J]. Eur J Pharm Sci, 2023, 184: 106415.
[41] Palmer B F, Clegg D J. SGLT2 inhibition and kidney potassium homeostasis[J]. Clin J Am Soc Nephrol, 2024, 19(3): 399-405.
[42] Neuen B L, Oshima M, Agarwal R, et al. Sodium-Glucose cotransporter 2 inhibitors and risk of hyperkalemia in people with type 2 diabetes: a meta-analysis of individual participant data from randomized, controlled trials[J]. Circulation, 2022, 145(19): 1460-1470.
[43] Weir M R, Slee A, Sun T, et al. Effects of canagliflozin on serum potassium in the CA Nagliflozin cardioVascular Assessment Study(CANVAS) Program[J]. Clin Kidney J, 2021, 14(5): 1396-1402.
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