Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Systematic literature review of clinical trials of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes and renal impairment (#317)

Merlin Thomas 1 , Päivi M. Paldánius 2 , Rajeev Ayyagari 3 , Siew H. Ong 2 , Per-Henrik Groop 4
  1. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
  2. Novartis Pharma AG, Basel, Switzerland
  3. Analysis Group Inc., Boston, MA, USA
  4. Helsinki University Central Hospital, Helsinki, Finland

Dipeptidyl peptidase-4 inhibitors (DPP-4i) have demonstrated utility in patients with normal renal function. However, more information is required on the efficacy and safety of DPP-4i in patients with moderate to severe renal impairment (RI). We performed a systematic literature review of the long-term efficacy and safety of DPP-4i in T2DM patients with RI.

We searched EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials, from database inception to November 2013, to identify randomised, placebo-controlled trials of DPP-4i in T2DM patients with RI. Eligible trials were of ≥12 weeks’ duration with ≥50 patients enrolled. Change in HbA1c and incidence of hypoglycaemic events (HEs) were evaluated.

Four placebo-controlled trials, of vildagliptin, saxagliptin, linagliptin or sitagliptin, were included; the first two had 52-week extensions. In the vildagliptin, saxagliptin and linagliptin trials, 74–82% patients received insulin at baseline, while 10% received insulin in the placebo-controlled trial with sitagliptin. After 52 weeks, vildagliptin, saxagliptin and linagliptin all significantly reduced HbA1c by 0.4–0.7% (baseline 7.7–8.7%) compared with placebo. HbA1c lowering was similar at 12 and 52 weeks in these studies, implying sustainable effects in this setting. In a 12-week study, a significant HbA1c reduction of 0.4% (baseline 7.7%) was observed in sitagliptin-treated patients compared with placebo. Vildagliptin-treated patients reported a similar incidence of HEs compared with placebo (23% vs 17%). Similarly, rate of HEs with saxagliptin was comparable with placebo (28% vs 29%). Linagliptin-treated patients reported a numerically higher rate of HEs compared with placebo (63% vs 49%), possibly indicating an overall higher HE rate. However, between-treatment differences in HEs were not significant for any of these molecules. No adverse effects on renal function, fluid retention or weight were observed.

Many patients with T2DM have RI, which makes diabetes management complicated and costly. These studies suggest DPP-4i have the potential to improve glycaemic control in this setting, without increased HEs or other adverse events.