PMID- 27038847
OWN - NLM
STAT- MEDLINE
DCOM- 20170130
LR  - 20170130
IS  - 1590-3729 (Electronic)
IS  - 0939-4753 (Linking)
VI  - 26
IP  - 4
DP  - 2016 Apr
TI  - DPP-4 inhibitors and cardiovascular disease in type 2 diabetes mellitus. 
      Expectations, observations and perspectives.
PG  - 273-84
LID - S0939-4753(16)00044-2 [pii]
LID - 10.1016/j.numecd.2016.03.002 [doi]
AB  - AIMS: Cardiovascular disease (CVD) is the greatest burden of type 2 diabetes 
      mellitus (T2DM) in terms of morbility, mortality and costs for individuals and 
      societies. Therefore, its prevention is a major goal in diabetes care. Optimal 
      treatment of hyperglycemia is certainly instrumental to CVD prevention. Optimal 
      treatment means both establishing the most appropriate glycemic target for the 
      given individual and selecting the medication(s) with the most favourable 
      benefit/safety ratio. CVD safety, if not a clear CVD benefit, is certainly 
      required for all antidiabetic agents. Dipeptidyl-peptidase-4 (DPP-4) inhibitors 
      are among the classes of antidiabetic agents most recently made available for 
      diabetes care. A major question to be addressed is the effect of these compounds 
      on CVD. Expectations were high for their mechanism of action, which targets also 
      post-prandial glucose and minimize hypoglycemia risk, thereby providing a sort of 
      global glucose control, and for some potentially beneficial extra-glycemic 
      effects. This article reviews the existing literature on this issue. DATA 
      SYNTHESIS: Data published so far document that DPP-4 inhibitors have a wide 
      spectrum of glycemic and extra-glycemic effects potentially reducing the risk of 
      CVD as well as favourable effects on intermediate or surrogate CVD endpoints. 
      These data heralded a better CVD outcome. Accordingly, pooling CVD safety data 
      from phase 3 and 4 studies conducted with DPP-4 inhibitors suggested that their 
      use might translate into a better CVD outcome. Data from three CVD outcome RCTs 
      with alogliptin, saxagliptin and sitagliptin documented no harm but did not show 
      any benefit on major CVD events. A modest but significant increased risk of 
      hospitalization for heart failure was observed with saxagliptin and with 
      alogliptin (only in subjects with no history of heart failure before 
      randomization) but not with sitagliptin. A study currently in progress with 
      linagliptin will provide further insights in the issue of CVD safety and benefit. 
      CONCLUSIONS: It should be considered that most alternative oral antidiabetic 
      agents generally do not possess a better CVD risk profile than DPP-4 inhibitors 
      and that some of them, indeed, should be used with caution because of potentially 
      adverse effects on heart and vasculature. Overall, the selection of antidiabetic 
      agent(s) with the most favourable CVD profile is mandatory but still challenging 
      in diabetes care.
CI  - Copyright (c) 2016 The Italian Society of Diabetology, the Italian Society for the 
      Study of Atherosclerosis, the Italian Society of Human Nutrition, and the 
      Department of Clinical Medicine and Surgery, Federico II University. Published by 
      Elsevier B.V. All rights reserved.
FAU - Bonora, Enzo
AU  - Bonora E
AD  - Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, 
      Verona, Italy. Electronic address: enzo.bonora@univr.it.
FAU - Cigolini, Massimo
AU  - Cigolini M
AD  - Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, 
      Verona, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160312
PL  - Netherlands
TA  - Nutr Metab Cardiovasc Dis
JT  - Nutrition, metabolism, and cardiovascular diseases : NMCD
JID - 9111474
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Piperidines)
RN  - 3X29ZEJ4R2 (Linagliptin)
RN  - 56HH86ZVCT (Uracil)
RN  - JHC049LO86 (alogliptin)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Cardiovascular Diseases/*drug therapy/etiology
MH  - Clinical Trials, Phase III as Topic
MH  - Clinical Trials, Phase IV as Topic
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/*adverse effects
MH  - Endpoint Determination
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/*adverse effects
MH  - Linagliptin/administration & dosage/adverse effects
MH  - Meta-Analysis as Topic
MH  - Observational Studies as Topic
MH  - Piperidines/administration & dosage/adverse effects
MH  - Randomized Controlled Trials as Topic
MH  - Risk Factors
MH  - Sitagliptin Phosphate/administration & dosage/adverse effects
MH  - Uracil/administration & dosage/adverse effects/analogs & derivatives
OTO - NOTNLM
OT  - Antidiabetic agents
OT  - Cardiovascular disease
OT  - Dipeptidyl peptidase 4 inhibitors
OT  - Type 2 diabetes mellitus
EDAT- 2016/04/04 06:00
MHDA- 2017/01/31 06:00
CRDT- 2016/04/04 06:00
PHST- 2014/09/20 00:00 [received]
PHST- 2016/03/04 00:00 [revised]
PHST- 2016/03/04 00:00 [accepted]
PHST- 2016/04/04 06:00 [entrez]
PHST- 2016/04/04 06:00 [pubmed]
PHST- 2017/01/31 06:00 [medline]
AID - S0939-4753(16)00044-2 [pii]
AID - 10.1016/j.numecd.2016.03.002 [doi]
PST - ppublish
SO  - Nutr Metab Cardiovasc Dis. 2016 Apr;26(4):273-84. doi: 
      10.1016/j.numecd.2016.03.002. Epub 2016 Mar 12.