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Meta-Analysis
. 2019 Mar;10(2):446-457.
doi: 10.1111/jdi.12876. Epub 2018 Jul 26.

Effects of sodium-glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta-analysis of randomized controlled trials

Bingshu Wu  1 , Hongzhi Zheng  1 , Jianqiu Gu  2 , Yan Guo  1 , Yixuan Liu  1 , Yingfang Wang  1 , Feng Chen  1 , Aolin Yang  1 , Jiabei Wang  1 , Hailong Wang  3 , Ying Liu  4 , Difei Wang  1
Affiliations
Meta-Analysis

Effects of sodium-glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta-analysis of randomized controlled trials

Bingshu Wu et al. J Diabetes Investig. 2019 Mar.

Abstract

Aims/introduction: In the present meta-analysis, we aimed to determine the effects of sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients.

Materials and methods: Randomized controlled trials were identified by searching the PubMed, Embase and Cochrane Library databases published before September 2017. The intervention group received SGLT-2i as add-on treatment to insulin therapy, and the control group received placebos in addition to insulin. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random-effects model.

Results: A total of 10 randomized controlled trials (n = 5,159) were eligible. The weighted mean differences for systolic blood pressure and diastolic blood pressure were -3.17 mmHg (95% CI -4.53, -1.80, I2 = 0%) and -1.60 mmHg (95% CI -2.52, -0.69, I2 = 0%) in the intervention groups. Glycosylated hemoglobin, fasting plasma glucose, postprandial glucose and daily insulin were also lower in the intervention groups, with relative weighted mean differences of -0.49% (95% CI -0.71, -0.28%, I2 = 92%), -1.10 mmol/L (95% CI -1.69, -0.51 mmol/L, I2 = 84%), -3.63 mmol/L (95% CI -4.36, -2.89, I2 = 0%) and -5.42 IU/day (95% CI -8.12, -2.72, I2 = 93%). The transformations of uric acid and bodyweight were -26.16 μmol/L (95% CI -42.14, -10.17, I2 = 80%) and -2.13 kg (95% CI -2.66, -1.60, I2 = 83%). The relative risk of hypoglycemia was 1.09 (95% CI 1.02, 1.17, P < 0.01). The relative risks of urinary tract and genital infection were 1.29 (95% CI 1.03, 1.62, P = 0.03) and 5.25 (95% CI 3.55, 7.74, P < 0.01).

Conclusions: The results showed that in the intervention group, greater reductions were achieved for blood pressure, glucose control, uric acid and bodyweight. This treatment regimen might therefore provide beneficial effects on the occurrence and development of cardiovascular events.

Keywords: Cardiovascular risk factors; Meta-analysis; Sodium-glucose cotransporter 2 inhibitor.

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Figures

Figure 1
Figure 1
Forest plot of randomized controlled trials: effect on systolic blood pressure. CI, confidence interval; SD, standard deviation.
Figure 2
Figure 2
Forest plot of randomized controlled trials: effect on diastolic blood pressure. CI, confidence interval; SD, standard deviation.
Figure 3
Figure 3
Forest plot of randomized controlled trials: effect on glycosylated hemoglobin. CI, confidence interval; SD, standard deviation.
Figure 4
Figure 4
Forest plot of randomized controlled trials: effect on fasting glucose plasma. CI, confidence interval; SD, standard deviation.
Figure 5
Figure 5
Forest plot of randomized controlled trials: effect on 2‐h postprandial glucose. CI, confidence interval; SD, standard deviation.
Figure 6
Figure 6
Forest plot of randomized controlled trials: effect on daily insulin. CI, confidence interval; SD, standard deviation.
Figure 7
Figure 7
Forest plot of randomized controlled trials: bodyweight. CI, confidence interval; SD, standard deviation.
Figure 8
Figure 8
Forest plot of randomized controlled trials: uric acid. CI, confidence interval; SD, standard deviation.
Figure 9
Figure 9
Subgroup analysis of diastolic blood pressure based on duration. CI, confidence interval; SD, standard deviation.
Figure 10
Figure 10
Subgroup analysis of daily insulin based on duration. CI, confidence interval; SD, standard deviation.
Figure 11
Figure 11
Subgroup analysis of body weight based on duration. CI, confidence interval; SD, standard deviation.
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