Chicago, IL—It is estimated that approximately 66% of patients with type 2 diabetes are at risk for declining renal function. A new double-blind, randomized trial of patients with type 2 diabetes and moderate-to-severe renal impairment—estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2—showed that the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin (Tradjenta) significantly reduced hemoglobin (Hb) A1c compared with placebo at 12 weeks (the primary end point); compared with glimepiride in the 40-week extension study, there was less hypoglycemia with linagliptin.
The trial, conducted in the United States and Europe, was presented at the 2013 American Diabetes Association annual meeting by lead investigator Markku Laakso, MD, PhD, Academy Professor, Department of Medicine, University of Eastern Finland, Kuopio. Of the patients (mean age, 67 years), 76% had diabetes duration of >10 years, 86% of them were taking insulin. The mean eGFR was 37 mL/min/1.73 m2.
For the primary efficacy end point analysis, patients were randomized to linagliptin 5 mg daily (N = 113) or to placebo (N = 122) for 12 weeks. For the 40-week extension study, the patients receiving placebo were switched to glimepiride 1 mg to 4 mg daily, and treatment continued until week 52 in both groups. The mean HbA1c at baseline was 8.08% in the linagliptin group and 8.03% in the placebo plus glimepiride group.
At 12 weeks, there was a greater mean reduction in baseline HbA1c with linagliptin of –0.53% compared with –0.11% with placebo plus glimepiride—a treatment difference of –0.42% (P <.001). HbA1c was also lower with linagliptin compared with placebo plus glimepiride during the 40-week extension.
The incidence of hypoglycemia was lower at 52 weeks with linagliptin compared with placebo plus glimepiride (57.9% vs 69.3%, respectively).
Drug-related adverse events were similar at 12 weeks (23.9%, linagliptin; 24.6%, placebo plus glimepiride) but were lower with linagliptin at 52 weeks (38.3% and 46.5%, respectively). Weight gain was also less with linagliptin at 52 weeks (0.06 kg vs 1.74 kg with placebo plus glimepiride).
There were no adverse changes in renal function or pancreatitis with linagliptin, and there were fewer renal and cardiovascular events with linagliptin than with placebo plus glimepiride.
Dr Laakso and his colleagues stated that these study results suggest that linagliptin may be a convenient, effective, and safe treatment for this patient population, noting that declining renal function comprises “a highly prevalent, complex, and vulnerable population in which other glucose-lowering treatments have important restrictions,” because they are primarily excreted by the kidneys and thus are contraindicated or require dose adjustment. Linagliptin is nearly exclusively excreted by nonrenal pathways, and thus does not require dose adjustment, which is in contrast to most DPP-4 drugs.