Haidinger et al AJT 2014; 14: 115-123 Presented by Dr Sourabh Chand

Efficacy and Safety of Vildagliptin in NODAT – a randomized, double-blind, placebo-controlled trial Haidinger et al AJT 2014; 14: 115-123 Presented by Dr Sourabh Chand QEHB ST6/Clinical Academic Fellow

Introduction • Post-transplant hyperglycaemia = morbidity, mortality • IFG • IGT • Ischaemic heart disease HR 1.39 • NODAT • premature graft failure – at 12yrs, 48% vs 70% without NODAT • Ischaemic heart disease RR 3.21 • Rx with T2DM strategiestraditionally • NODAT – insulin sensitivity vs secretion

12% >10.9 GFR<30 LFTS Stable 3 months renal function OGTT – 0 & 3 months OGTT – 0 & 3 months 1°outcome: 1.1mmol/l (20) difference STOP DRUG 1 month, then OGTT 4 months – FPG, HbA1c, fasting insulin, rate S/E, ∆GFR, ACR, ∆LFTs & CNI levels 2°outcomes:

Primary outcome • OGTT 4 months no difference from baseline • Lifestyle at 4 months (placebo) -2.2 mmol/l (±6) -0.91mmol/l -0.18mmol/l -4mmol/l -0.3mmol/l

HbA1c significantly different at 4 months (unsurprisingly) – “robust improvement”

Insgenic Index - insulin secretion as a marker of β cell function

Will changes in lipid profile affect CV outcomes (esp metabolic syndrome)

Conclusions • DPP-4 inhibitors stabilise incretin hormone GLP-1 • Reduction in postprandial hyperglycaemia • Evidenced by 2hr OGTT results • No increase in BMI, relatively safe profile • Maybe more importantly in NODAT β cell protective effect • No effect on short-term effects on insulin sensitivity

Remaining questions • Long term effects • Especially on CV outcome • Lipid profile • Compare other hypoglycaemics (eg metformin (eGFR)) • Is this a particular NODAT or metabolic syndrome profile? • 5 yrs post transplant, genetics, pancreatic decompensation • Deceased vs live donor • IFG/IGT patients • Other parameters • HLA mismatch, rejection episodes, multivariate analysis (∆weight, diagnoses, Bp)

Haidinger et al AJT 2014; 14: 115-123 Presented by Dr Sourabh Chand