What is the long-term CV effect of adding a GLP-1RA to insulin?

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Takeaway

  • Adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to insulin may reduce cardiovascular (CV) events and prolong survival in overweight patients with type 2 diabetes (T2D).

Why this matters

  • Many patients with T2D eventually require insulin to control glycemia, but this can lead to weight gain and possible increased CV risk.

Study design

  • Retrospective cohort study; 18,227 patients with insulin-treated T2D, UK General Practices database.
  • Propensity score-matched analysis conducted among 1793 receiving insulin alone, 1793 receiving insulin+GLP-1RA.  
  • Funding: None.

Key results

  • Adjusted risk for major adverse CV events (all-cause mortality, nonfatal myocardial infarction [MI], nonfatal stroke) 36% lower with GLP-1RA vs without (adjusted HR [aHR], 0.64; 95% CI, 0.42-0.98).
  • Risk for all-cause mortality 65% less (aHR, 0.35; 95% CI, 0.17-0.73).
  • Risk for composite CV outcomes (nonfatal acute MI, nonfatal stroke) 24% less (aHR, 0.76; 95% CI, 0.41-1.42).
  • Nonsignificant increase in heart failure hospitalization with GLP-1RAs (aHR, 1.22; 95% CI, 0.76-1.94).
  • HbA1c significantly reduced in both groups with no differences between them (−0.34% vs −0.41%; P=.33 at 36 months).
  • Significant weight increases in both treatment groups in first 6 months and up to 12 months in the non-GLP-1RA group, but no subsequent difference.

Limitations

  • Possible residual confounding.
  • Low number of reported outcomes.