An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials.
OBJECTIVE
To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase-IV (DPP-4) inhibitors.


METHODS
Data were pooled from 38 studies where vildagliptin was given for > or =12 to > 104 weeks in patients with T2DM. Absolute and exposure-adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated.


RESULTS
There were > 7000 subject-years of exposure (SYE) to vildagliptin 50 mg bid and > 6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI: [0.80, 1.93]) and 1.19 (95% CI: [0.29, 4.90]), respectively. The exposure-adjusted incidences of markedly elevated hepatic enzymes and for enzyme elevations with bilirubin > or = 2x ULN with vildagliptin 50 mg bid were < or = those in the ACs group. For hepatic and pancreatitis-related AEs, the ORs for vildagliptin 50 mg bid were 0.87 (95% CI: [0.64, 1.19]) and 0.70 (95% CI: [0.26, 1.88]), respectively, and for any AE in the infections and infestations SOC, this was 1.04 (95% CI: [0.96, 1.13]). The incidences of skin-related AEs were low and the risk with vildagliptin 50 mg bid was not significantly different from ACs [(OR = 1.10 (95% CI: [0.80, 1.51])].


CONCLUSIONS
The present meta-analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug-induced liver injury, pancreatitis, infections or skin-related toxicity.
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. monica.ligueros@novartis.com
M
M
Ligueros-Saylan
J E
JE
Foley
A
A
Schweizer
A
A
Couturier
W
W
Kothny
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D002986:Clinical Trials as Topic; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000150:complications*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007107:Immune System / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009570:Nitriles / Q000009:adverse effects*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000009:adverse effects*; D012307:Risk Factors; D012867:Skin / Q000187:drug effects*; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane