Efficacy of vildagliptin therapy in combination with insulin in patients with type 2 diabetes and severe renal impairment — ASN Events
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Efficacy of vildagliptin therapy in combination with insulin in patients with type 2 diabetes and severe renal impairment (#46)

Richard Simpson 1 , Joseph Proietto 2 , Glenn Ward 3 , Joey Kaye 4 , P-H Groop 5 , V Lukashevich 6
  1. ECRU, Box Hill, Australia
  2. University of Melbourne, Melbourne, Australia
  3. St Vincents, Melbourne, VIC, Australia
  4. Sir Charles Gairdner Hospital, Nedlands, Australia
  5. Helsinki University Hospital, Helsinki, Finland
  6. Novartis Pharmaceuticals Corporation, East Hanover, USA

Background and aims: Vildagliptin, a potent and selective DPP-4 inhibitor, improves islet function by increasing α- and β-cell responsiveness to glucose. The question rises whether patients with renal impairment, where β-cell sensitivity to glucose is often severely impaired, will be responsive to vildagliptin.
Materials and methods: The efficacy of vildagliptin in a subgroup of T2DM patients with severe renal impairment [estimated GFR (eGFR) < 30 ml/ min per (1.73 m2) according to MDRD] inadequately controlled on insulin (HbA1c of ≥ 6.5 and ≤ 10 %) from a double blind placebo controlled study was analyzed. Vildagliptin 50 mg od or matching placebo was added to the background therapy that remained unchanged through 24-week treatment. Efficacy was assessed as HbA1c reductions at study endpoint from baseline and versus placebo using ANCOVA model. Safety and tolerability were also evaluated.
Results: 178 patients with severe renal impairment received insulin treatment (86%) or insulin treatment with other oral anti-diabetic drugs (OADs). Mean age was 64 years, 48% female, and mean duration of diabetes was 19 years. Table 1 demonstrates mean HbA1c reduction in vildagliptin-treated patients by -0.87% (baseline 7.7%), with placebo-subtracted reduction -0.59% (p<0.0001). Hypoglycemia overall and severe hypoglycemic events were reported at a similar rate in vildagliptin and placebo patients (19% vs 14% and 2% vs 3%) in spite of considerably greater HbA1c reduction in the vildagliptin group. The overall incidences of AEs and SAEs were similar for vildagliptin and placebo (79% vs. 77% and 19% and 24%). 
Conclusion: The mean HbA1 reduction of 0.87% from a baseline of 7.7% in insulin requiring patients with longstanding T2DM and severe renal impairment is consistent with the drops in HbA1c that have been reported previously in vildagliptin-treated patients with more recent onset of diabetes and appears to be efficacious.

Table 1. ANCOVA results for change in HbA1c (%) from baseline to rescue censored endpoint treatment (full analysis set)

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Clinical Trial Registration Number: NCT00646542
Supported by: Novartis Pharmaceuticals