Comparison of vildagliptin with placebo in a 24-week study of 221 patients with type 2 diabetes and severe renal impairment (eGFR<30) — ASN Events
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Comparison of vildagliptin with placebo in a 24-week study of 221 patients with type 2 diabetes and severe renal impairment (eGFR<30) (#303)

Joseph Proietto 1 , Richard W Simpson 2 , Glenn Ward 3 , Joey Kaye 4 , Per Henrik Groop 5 , Valentina Lukashevich 6
  1. University of Melbourne, Melbourne, Vic, Australia
  2. Monash University, Melbourne, Victoria, Australia
  3. St Vincent's Hospital, Melbourne, Victoria, Australia
  4. Sir Charles Gairner Hospital, Perth, Western Australia, Australia
  5. Helsinki University Hospital, Helsinki, Finland
  6. Novartis Pharmaceuticals Corporation, East Hanover, USA

Background and aims: Patients with type 2 diabetes (T2DM) have an increased prevalence of decreased kidney function, which progresses with increasing disease duration. Pharmacokinetic data for vildagliptin (DPP-4 inhibitor) indicated an approximately 2-fold increased exposure in patients with severe renal impairment. It was therefore of interest to assess the safety and tolerability of vildagliptin as well as its efficacy in patients with T2DM and severe renal impairment.

Materials and methods: In a 24-week, multicenter, randomized, doubleblind, parallel-group, placebo-controlled study, 221 patients with T2DM and severe renal impairment [estimated GFR (eGFR) <30 ml/min/1.73 m2 according to MDRD] were randomized to vildagliptin 50 mg od (N=124) and placebo (N=97). Oral antidiabetic or insulin therapy present at enrollment (97.3%) was continued throughout the study. The primary endpoint was safety and tolerability; overall and specific safety data is presented. The change in HbA1c from baseline to study endpoint was analyzed by ANCOVA.

Results: Baseline and demographic characteristics: mean eGFR = 21.5 ml/min/1.73 m2, mean age = 64.3 years, mean BMI = 30.0 kg/m2, mean HbA1c = 7.7%, mean disease duration = 18.1 years and 80.5% of patients insulin treated. Overall AEs, serious AEs, discontinuations due to AEs and deaths were reported with a comparable frequency in both groups (Table 1). There were no clinically relevant or statistically significant differences between treatment groups for hepatic-related AEs (0.8% with vildagliptin vs. 1.0% with placebo; p>0.999), skin-related AEs (2.4% vs. 6.2%; p=0.185), oedema-related AEs (16.9% vs. 18.6%; p=0.859) and pancreatitis-related AEs (0% in both groups). One patient in each group (0.8% vs 1.1%) had treatment emergent persistent ALT/AST elevations ?3xULN. Mean HbA1c was reduced, placebo-subtracted reduction being -0.56% (95% CI -0.83 to -0.30, p<0.0001).

Conclusion: Vildagliptin 50 mg od is well tolerated and efficacious in T2DM patients with severe renal impairment.

Table 1. Overall safety in T2DM patients with severe renal impairment (Safetyset)

Vildagliptin 50 mg od

N=124

n(%)

Placebo

N=97

n(%)

AEs

90 (72.6)

72 (74.2)

SAEs

23 (18.5)

20 (20.6)

Discontinuation due to AEs

11 (8.9)

6 (6.2)

Deaths

3 (2.4)

4 (4.1)

AE = adverse event; SAE = serious adverse event

Clinical Trial Registration Number: NCT00646542

Supported by: Novartis Pharmaceuticals