Sodium-glucose co-transporter inhibitors in insulin-treated diabetes: a meta-analysis

in European Journal of Endocrinology
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  • 1 J Ferreira, CIC-P, Lorraine European University Centre, Nancy, France
  • 2 A Oliveira, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal
  • 3 F Saraiva, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal
  • 4 F Vasques-Nóvoa, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal
  • 5 A Leite-Moreira, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal

Correspondence: Joao Ferreira, Email: jp7ferreira@hotmail.com
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Background: Patients with insulin-treated type 2 diabetes (T2D) have a high risk of major adverse cardiovascular events. Sodium-glucose cotransporter inhibitors (SGLTi) improve outcomes without hypoglycemic risk.

Aims: To study the effect of SGLTi in patients with T2D with and without background insulin-treatment in outcome-driven RCTs.

Methods: Random effects models.

Results: A total of 54,374 patients with T2D were included in the analysis, of which 26,551 (48.8%) were treated with insulin. For 3P-MACE in patients without insulin treatment, the HR (95%CI) for the effect of SGLTi vs. placebo was 0.93 (0.81-1.05), with moderate heterogeneity (I2 =49.2%, Q statistic P =0.11). In insulin-treated patients, the HR (95%CI) was 0.88 (0.82-0.95), without evidence of heterogeneity (I2 =0.0%, Q statistic P =0.91). The pooled effect evidenced a 10% reduction of 3P-MACE with SGLTi (HR 0.90, 95%CI 0.85-0.96), without SGLTi-by-insulin interactionP=0.53. For the composite outcome of HF hospitalisation or cardiovascular death in patients without insulin treatment, the HR (95%CI) for the effect of SGLTi vs. placebo was 0.77 (0.61-0.92), with marked heterogeneity (I2 =66.8%, Q statistic P =0.02). In insulin-treated patients, the HR (95%CI) was 0.77 (0.68-0.86), without significant heterogeneity (I2 =31.7%, Q statistic P =0.25). The pooled effect evidenced a 23% reduction of HF hospitalisations or cardiovascular death with SGLTi (HR 0.77, 95%CI 0.68-0.85), without SGLTi -by-insulin interactionP=0.98.

Conclusion:SGLTi reduce cardiovascular events regardless of insulin use. However, the treatment effect is more homogeneous among insulin-treated patients, supporting the use of SGLTi for the treatment of patients with T2D requiring insulin for glycemic control.

 

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