TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial

The Lancet, 04/30/2012

Burant CF et al. - TAK-875 significantly improved glycaemic control in patients with type 2 diabetes with minimum risk of hypoglycaemia. The results show that activation of free fatty acid receptor 1 (FFAR1) is a viable therapeutic target for treatment of type 2 diabetes.

Methods

  • The authors undertook a phase 2, randomised, double-blind, and placebo-controlled and active-comparator-controlled trial in outpatients with type 2 diabetes who had not responded to diet or metformin treatment.
  • Patients were randomly assigned equally to receive placebo, TAK-875 (6.25, 25, 50, 100, or 200 mg), or glimepiride (4 mg) once daily for 12 weeks.
  • Patients and investigators were masked to treatment assignment.
  • The primary outcome was change in haemoglobin A1c (HbA1c) from baseline.
  • Analysis included all patients randomly assigned to treatment groups who received at least one dose of double-blind study drug.

Results

  • 426 patients were randomly assigned to TAK-875 (n=303), placebo (n=61), and glimepiride (n=62).
  • At week 12, significant least-squares mean reductions in HbA1c from baseline occurred in all TAK-875 (ranging from -1.12% [SE 0.113] with 50 mg to -0.65% [0.114] with 6.25 mg) and glimepiride (-1.05% [SE 0.111]) groups versus placebo (-0.13% [SE 0.115]; p value range 0.001 to <0.0001).
  • Treatment-emergent hypoglycaemic events were similar in the TAK-875 and placebo groups (2% [n=7, all TAK-875 groups] vs 3% [n=2]); significantly higher rates were reported in the glimepiride group (19% [n=12]; p value range 0.010—0.002 vs all TAK-875 groups).
  • Incidence of treatment-emergent adverse events was similar in the TAK-875 overall (49%; n=147, all TAK-875 groups) and placebo groups (48%, n=29) and was lower than in the glimepiride group (61%, n=38).

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