PMID- 30876392
OWN - NLM
STAT- MEDLINE
DCOM- 20200129
LR  - 20200309
IS  - 1471-2261 (Electronic)
IS  - 1471-2261 (Linking)
VI  - 19
IP  - 1
DP  - 2019 Mar 15
TI  - Review of the cardiovascular safety of dipeptidyl peptidase-4 inhibitors and the 
      clinical relevance of the CAROLINA trial.
PG  - 60
LID - 10.1186/s12872-019-1036-0 [doi]
LID - 60
AB  - BACKGROUND: Cardiovascular (CV) disease (CVD) is a well-recognized complication 
      of type 2 diabetes mellitus (T2DM) and there is a clinical need for 
      glucose-lowering therapies that do not further increase CV risk in this 
      population. Although sulfonylureas (SUs) may be used as second-line therapy for 
      patients requiring additional therapy after first-line metformin to improve 
      glycemic control, their long-term effects on CV outcomes remain uncertain, and a 
      wide range of alternative agents exist including dipeptidyl peptidase-4 (DPP-4) 
      inhibitors. METHODS: Literature searches in PubMed (2013-2018) were conducted 
      with terms for DPP-4 inhibitors combined with CV terms, with preference given to 
      cardiovascular outcomes trials (CVOTs). Reference lists from retrieved articles 
      and diabetes guidelines were also considered. RESULTS: This narrative review 
      discusses current evidence for the CV safety of these agents, describes the 
      long-term CV effects of DPP-4 inhibitors, including effects on CV events, 
      mortality, the risk for heart failure hospitalization, and highlights the need 
      for further research into the CV effects of SU therapy. Although SUs remain a 
      treatment option for T2DM, the long-term effects of these agents on CV outcomes 
      are unclear, and further long-term studies are required. For DPP-4 inhibitors, 
      uncertainties have been raised about their long-term effect on hospitalization 
      for heart failure in light of the results of SAVOR-TIMI 53, although the findings 
      of other DPP-4 inhibitor CVOTs in T2DM and data analyses have suggested these 
      agents do not increase the occurrence of adverse CV outcomes. CONCLUSIONS: Based 
      on recent CVOTs and guideline updates, the choice of add-on to metformin therapy 
      for patients with T2DM and established CV disease should be a sodium-glucose 
      co-transporter-2 inhibitor or a glucagon-like peptide-1 agonist with proven CV 
      benefit. Additional treatment options for those individuals who require therapy 
      intensification, as well as in patients with T2DM and without established CVD 
      include DPP-4 inhibitors and SUs. Since few head-to-head trials have compared the 
      effects of different oral glucose-lowering agents on CV outcomes in T2DM, with 
      most CVOTs using placebo as a comparator, the CAROLINA trial will provide 
      important information on the comparative CV safety of a commonly prescribed SU 
      and a DPP-4 inhibitor.
FAU - Santamarina, Marile
AU  - Santamarina M
AUID- ORCID: 0000-0002-0439-5279
AD  - Gregory School of Pharmacy, Palm Beach Atlantic University, 901 South Flagler 
      Drive, West Palm Beach, FL, 33416, USA. MARILE_SANTAMARINA@pba.edu.
FAU - Carlson, Curt J
AU  - Carlson CJ
AD  - Gregory School of Pharmacy, Palm Beach Atlantic University, 901 South Flagler 
      Drive, West Palm Beach, FL, 33416, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190315
PL  - England
TA  - BMC Cardiovasc Disord
JT  - BMC cardiovascular disorders
JID - 100968539
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Sulfonylurea Compounds)
SB  - IM
MH  - Biomarkers/blood
MH  - Blood Glucose/*drug effects/metabolism
MH  - Cardiovascular Diseases/diagnosis/*epidemiology/mortality/therapy
MH  - Clinical Trials as Topic
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/mortality
MH  - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use
MH  - Disease Progression
MH  - Hospitalization
MH  - Humans
MH  - Risk Assessment
MH  - Risk Factors
MH  - Sulfonylurea Compounds/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC6419798
OTO - NOTNLM
OT  - Cardiovascular diseases
OT  - DPP-4 inhibitors
OT  - Linagliptin
OT  - Sulfonylureas
OT  - Type 2 diabetes mellitus
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTEREST: The authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2019/03/17 06:00
MHDA- 2020/01/30 06:00
PMCR- 2019/03/15
CRDT- 2019/03/17 06:00
PHST- 2018/10/01 00:00 [received]
PHST- 2019/02/27 00:00 [accepted]
PHST- 2019/03/17 06:00 [entrez]
PHST- 2019/03/17 06:00 [pubmed]
PHST- 2020/01/30 06:00 [medline]
PHST- 2019/03/15 00:00 [pmc-release]
AID - 10.1186/s12872-019-1036-0 [pii]
AID - 1036 [pii]
AID - 10.1186/s12872-019-1036-0 [doi]
PST - epublish
SO  - BMC Cardiovasc Disord. 2019 Mar 15;19(1):60. doi: 10.1186/s12872-019-1036-0.