Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes

Diabet Med. 2010 Dec;27(12):1409-19. doi: 10.1111/j.1464-5491.2010.03131.x.

Abstract

Aims: The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, linagliptin, added to ongoing metformin therapy, were assessed in patients with Type 2 diabetes who had inadequate glycaemic control (HbA(1c) ≥ 7.5 to ≤ 10%; ≥ 58.5 to ≤ 85.8 mmol/mol) with metformin alone.

Methods: Patients (n=333) were randomized to receive double-blind linagliptin (1, 5 or 10 mg once daily) or placebo or open-label glimepiride (1-3 mg once daily). The primary outcome measure was the change from baseline in HbA(1c) at week 12 in patients receiving combination therapy compared with metformin alone.

Results: Twelve weeks of treatment resulted in a mean (sem) placebo-corrected lowering in HbA(1c) levels of 0.40% (± 0.14); 4.4 mmol/mol (± 1.5) for 1 mg linagliptin, 0.73% (± 0.14); 8.0 mmol/mol (± 1.5) for 5 mg, and 0.67% (± 0.14); 7.3 mmol/mol (± 1.5) for 10 mg. Differences between linagliptin and placebo were statistically significant for all doses (1 mg, P = 0.01; 5 mg and 10 mg, P < 0.0001). The change in mean (sem) placebo-corrected HbA(1c) from baseline was -0.90% (± 0.13); -9.8 mmol/mol (± 1.4) for glimepiride. Adjusted and placebo-corrected mean changes in fasting plasma glucose were -1.1 mmol/l for linagliptin 1 mg (P = 0.002), -1.9 mmol/l for 5 mg and -1.6 mmol/l for 10 mg (both P < 0.0001). One hundred and six (43.1%) patients reported adverse events; the incidence was similar across all five groups. There were no hypoglycaemic events for linagliptin or placebo, whereas three patients (5%) receiving glimepiride experienced hypoglycaemia.

Conclusions: The addition of linagliptin to ongoing metformin treatment in patients with Type 2 diabetes was well tolerated and resulted in significant and clinically relevant improvements in glycaemic control, with 5 mg linagliptin being the most effective dose.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / drug effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Linagliptin
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacokinetics
  • Middle Aged
  • Purines / administration & dosage*
  • Purines / pharmacokinetics
  • Quinazolines / administration & dosage*
  • Quinazolines / pharmacokinetics
  • Treatment Outcome

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • hemoglobin A1c protein, human
  • Linagliptin
  • Metformin