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

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

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology*
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Incidence
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors