sitagliptin-phosphate and Carotid-Artery-Diseases

Accumulated evidence shows that some antidiabetic agents attenuate the progression of carotid atherosclerosis assessed as intima-media thickness (IMT). Although some studies have demonstrated an inhibitory effect of dipeptidyl peptidase-4 inhibitors on carotid IMT progression, in the PROLOGUE study sitagliptin failed to slow progression relative to conventional therapy for 24 months. We hypothesized that differences in the concomitant antidiabetic agents between the groups have influenced the progression of carotid IMT. We performed a post hoc analysis of the PROLOGUE study using subgroups stratified by concomitant antidiabetic agents. Although no subgroup with any combination of agents in the overall patients showed a significant difference between sitagliptin group and conventional therapy group in the changes from baseline in mean common carotid artery (CCA)-IMT at 24 months, a significant attenuation of mean CCA-IMT progression was observed in the sitagliptin group relative to conventional therapy group only in three combination subgroups aged < 70 years, namely no thiazolidinedione; no thiazolidinedione or biguanide; and no thiazolidinedione, biguanide or α-glucosidase inhibitor, even after adjustment for multiple confounding factors. In the three subgroups, no significant difference between sitagliptin group and conventional therapy group in the changes from baseline in HbA1c at 24 months was detected. Our data suggest that some concomitant agents, whose prescription frequencies were increased in the conventional therapy group, may have masked the inhibitory effect of sitagliptin on carotid IMT progression in the PROLOGUE study.

Topics: Aged; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Disease Progression; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Prospective Studies; Sitagliptin Phosphate; Time Factors; Treatment Outcome

Ultrasonic gray-scale median (GSM) of the carotid wall reflects its composition and low-GSM carotid plaque is considered to be vulnerable. This study aimed to evaluate the effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue characteristics of the carotid wall, in patients with type 2 diabetes mellitus (T2DM).. This is a post hoc sub-analysis using data obtained from the SPIKE trial, a randomized controlled trial that demonstrated the beneficial effect of sitagliptin on the progression of carotid intima-media thickness in patients with T2DM. A total of 274 T2DM patients with no past history of apparent cardiovascular disease (137 in the sitagliptin treatment group and 137 in the conventional treatment group) were enrolled. The primary outcome was the change from baseline in mean GSM-CCA during the 104-week treatment period.. The mean GSM-CCA significantly increased in the sitagliptin treatment group (adjusted ΔGSM = 2.40 ± 1.19 [mean ± SE], p = 0.044) but not in the conventional treatment group (adjusted ΔGSM = 1.32 ± 1.19, p = 0.27). However, there was no significant difference in changes in mean GSM-CCA between the treatment groups.. A post hoc sub-analysis suggests that the tissue characteristics of the carotid arterial wall were improved in the sitagliptin treatment group during the 104-week treatment period, but not in the conventional treatment group. However, there was no between-group difference in the changes of GSM values between the two treatment groups. Prespecified studies with large sample sizes would be necessary to confirm our findings. Trial registration UMIN000028664, Registered 15 August 2017 ("retrospectively registered").

Topics: Aged; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Japan; Male; Middle Aged; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Sitagliptin Phosphate; Time Factors; Treatment Outcome

Blood glucose fluctuations have been found to be relevant to the progression of atherosclerosis in patients with type 2 diabetes and to be more detrimental for the development of atherosclerosis than the sustained hyperglycemia. We aim at evaluating the effect of blunted daily acute glucose fluctuations by DPP-IV inhibitors on intima-media thickness (IMT), a surrogate marker for early atherosclerosis.. Data from a 12-week prospective, randomized, open-label parallel group trial with a blinded-endopoint study on 90 patients with DMT2, assessing the role of Dipeptidyl Peptidase-4 inhibition in lowering oxidative stress and inflammation by reducing daily acute glucose fluctuations (MAGE), were included in the present analysis.. Administration of both sitagliptin and vildagliptin treatment resulted in a significant decline in IMT. Indeed, vs baseline data Vildagliptin vs Sitagliptin resulted in a greater IMT reduction. After 3 months therapy changes in IMT significantly correlated with changes in MAGE but not with change in HbA1c in the whole population. Only change in MAGE and LDL plasma levels resulted to be independent predictors of the reduced carotid intima-media thickness after adjusting for conventional cardiovascular risk factors in patients with type 2 diabetes. Significant correlations between change in MAGE, change in IMT and change in fasting and interprandial inflammation score and nitrotyrosine plasma levels were found.. Reduction of glucose excursion due to DPP-IV inhibitors administration, may prevent atherosclerosis progression in patients with type 2 diabetes probably through the reduction of daily inflammation and oxidative stress.

Topics: Adamantane; Atherosclerosis; Blood Glucose; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cytokines; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Inflammation; Nitriles; Oxidative Stress; Prospective Studies; Pyrazines; Pyrrolidines; Sitagliptin Phosphate; Triazoles; Tyrosine; Vildagliptin

The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis.

Topics: Aged; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulins; Male; Middle Aged; Risk Factors; Sitagliptin Phosphate

Figure 1 shows differences in treatment-induced delta change in carotid IMT relative to baseline, according to various pre-defined risk factors for atherosclerosis. These data suggest that treatment with DPP-4 inhibitors seem to prevent the progression of carotid atherosclerosis regardless of disease burden.

Topics: Aged; Carotid Artery Diseases; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Male; Middle Aged; Sitagliptin Phosphate; Treatment Outcome