PMID- 29264572
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220311
IS  - 2472-1972 (Print)
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 1
IP  - 9
DP  - 2017 Sep 1
TI  - Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of 
      Dipeptidyl Peptidase-4 by Sitagliptin.
PG  - 1168-1178
LID - 10.1210/js.2017-00312 [doi]
AB  - CONTEXT: Patients with diabetes often have comorbidities such as hypertension. It 
      is not known how individual characteristics influence response to dipeptidyl 
      peptidase-4 (DPP4) inhibitors. OBJECTIVE: We tested the hypothesis that 
      individual characteristics, sitagliptin dose, and genetic variability in DPP4 
      influence DPP4 activity during sitagliptin. DESIGN AND SETTING: Post hoc analysis 
      of clinical and laboratory data from individuals randomized to sitagliptin versus 
      placebo in crossover studies. PATIENTS AND INTERVENTIONS: Sixty-five subjects [27 
      with type 2 diabetes mellitus (T2DM) and hypertension, 38 healthy controls] were 
      randomized to 100 mg/d sitagliptin or 200 mg sitagliptin and matching placebo in 
      double-blind, crossover fashion. Fasting blood was obtained at baseline and 60 to 
      180 minutes after sitagliptin or placebo. MAIN OUTCOME MEASURES: DPP4 activity 
      and antigen during placebo and sitagliptin and DPP4 inhibition during 
      sitagliptin. RESULTS: Sitagliptin 100 mg/d was less effective at inhibiting DPP4 
      activity in individuals with T2DM and hypertension than in healthy controls (P = 
      0.001, percent inhibition). In healthy controls, 100 mg/d sitagliptin was not as 
      effective as single-dose 200 mg sitagliptin (P = 0.001, percent inhibition). DPP4 
      genotypes rs2909451 TT (P = 0.02) and rs759717 CC (P = 0.02) were associated with 
      DPP4 activity during sitagliptin. In multivariable analyses, T2DM with 
      hypertension, sitagliptin dose, age, systolic blood pressure, DPP4 activity 
      during placebo, and rs2909451 genotype were significantly associated with DPP4 
      activity during sitagliptin. CONCLUSIONS: Sitagliptin is less effective in 
      inhibiting DPP4 in individuals with T2DM and hypertension than in healthy 
      controls. Higher doses of DPP4 inhibitors may be required in patients with the 
      metabolic syndrome.
FAU - Wilson, Jessica R
AU  - Wilson JR
AD  - Vanderbilt University Medical Center, Department of Medicine, Division of 
      Diabetes, Endocrinology, and Metabolism, Nashville, Tennessee 37232.
FAU - Shuey, Megan M
AU  - Shuey MM
AD  - Vanderbilt University, Nashville, Tennessee 37232.
FAU - Brown, Nancy J
AU  - Brown NJ
AD  - Vanderbilt University Medical Center, Department of Medicine, Division of 
      Clinical Pharmacology, Nashville, Tennessee 37232.
FAU - Devin, Jessica K
AU  - Devin JK
AD  - Vanderbilt University Medical Center, Department of Medicine, Division of 
      Diabetes, Endocrinology, and Metabolism, Nashville, Tennessee 37232.
LA  - eng
GR  - T32 DK007061/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000445/TR/NCATS NIH HHS/United States
GR  - T32 GM007569/GM/NIGMS NIH HHS/United States
GR  - K23 HL119602/HL/NHLBI NIH HHS/United States
GR  - UL1 RR024975/RR/NCRR NIH HHS/United States
GR  - UL1 TR002243/TR/NCATS NIH HHS/United States
GR  - R01 HL125426/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20170801
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC5686657
OTO - NOTNLM
OT  - DPP4
OT  - dipeptidyl peptidase-4 inhibition
OT  - hypertension
OT  - metabolic syndrome
OT  - sitagliptin
OT  - type 2 diabetes mellitus
EDAT- 2017/12/22 06:00
MHDA- 2017/12/22 06:01
PMCR- 2017/08/01
CRDT- 2017/12/22 06:00
PHST- 2017/07/10 00:00 [received]
PHST- 2017/07/27 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/22 06:01 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - JS_201700312 [pii]
AID - 10.1210/js.2017-00312 [doi]
PST - epublish
SO  - J Endocr Soc. 2017 Aug 1;1(9):1168-1178. doi: 10.1210/js.2017-00312. eCollection 
      2017 Sep 1.