For patients with T2D taking dulaglutide, does metformin matter for CV risk?

  • Ferrannini G & al.
  • Eur Heart J
  • 16 Nov 2020

  • curated by Miriam Tucker
  • Clinical Essentials
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Takeaway

  • Dulaglutide’s cardiovascular (CV) benefit in patients with type 2 diabetes (T2D) at high CV risk or with established CV disease is similar with or without baseline metformin use.

Why this matters

  • Recent European guidelines advise glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors as first-line glucose-lowering therapy for these patients, but the role of baseline metformin use was unclear.

Study design

  • Post hoc subgroup analysis of REWIND trial: 9901 patients with T2D and high CV risk/previous CV event randomly assigned to receive 1.5 mg/week dulaglutide or placebo; 81% receiving baseline metformin.
  • Primary outcome was first of composite nonfatal myocardial infarction, nonfatal stroke, and death from CV or unknown causes.
  • Funding: Eli Lilly and Company.

Key results

  • During a median 5.4 years of follow-up, primary outcome occurred in 12% with vs 15% without metformin.
  • Primary endpoint was reduced with dulaglutide: HR, 0.88 (95% CI, 0.79-0.99).
    • Similar effects with/without metformin (Pinteraction=.26).
  • Results for the primary outcome were similar after adjustment for independent determinants of metformin use:
    • HR, 0.92 (95% CI, 0.81-1.05) with metformin.
    • HR, 0.78 (95% CI, 0.61-0.99) without (Pinteraction=.18).
  • No differences in secondary outcomes: microvascular composite endpoint (Pinteraction=.17), all-cause death (Pinteraction=.43), or heart failure (Pinteraction=.77).

Limitations

  • Selected high-risk population.
  • Post hoc analysis.  
  • Small no-metformin group.
  • Possible effect of other glucose-lowering medications.