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

Autores da FMUP

• João Pedro Melo Marques Pinho Ferreira

  Autor

• Francisca Almeida Saraiva

  Autor

• Francisco Aguiar Vasques Novoa Faria

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Oliveira, AC

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

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 hypoglycaemic 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 (I-2 = 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 (I-2 =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 interaction P = 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 (I-2 = 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 (I-2 = 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 interaction P = 0.98. Conclusion: SGLTi reduces 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 glycaemic control.

Keywords

• Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Sodium-Glucose Transport Proteins; Treatment Outcome; insulin; placebo; sodium glucose cotransporter inhibitor; antidiabetic agent; insulin; sodium glucose cotransporter; aged; Article; cardiovascular disease; cardiovascular mortality; confidence interval; female; glycemic control; hazard ratio; heart death; hospitalization; human; insulin treatment; male; meta analysis; non insulin dependent diabetes mellitus; priority journal; protein function; cardiovascular disease; complication; non insulin dependent diabetes mellitus; randomized controlled trial (topic); treatment outcome