scholarly journals Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation

2022 ◽  
Author(s):  
Khalaf Kridin ◽  
Orly Avni ◽  
Giovanni Damiani ◽  
Dana Tzur Bitan ◽  
Erez Onn ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Statistical Significance ◽  
Dipeptidyl Peptidase ◽  
Diabetic Control ◽  
Population Based ◽  
Dipeptidyl Peptidase Iv ◽  
Response Analysis ◽  
Diabetic Patients ◽  
Predisposing Factor ◽  
Culprit Drug

AbstractThe timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case–control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46–2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69–4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33–1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1–2 years after commencing the drug (OR, 2.66; 95% CI, 1.97–3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09–1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30–2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

scholarly journals Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

2021 ◽  
Author(s):  
Khalaf Kridin ◽  
Jennifer E. Hundt ◽  
Ralf J. Ludwig ◽  
Kyle T. Amber ◽  
Dana Tzur Bitan ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Statistical Significance ◽  
Large Population ◽  
Underlying Mechanism ◽  
Population Based ◽  
Control Subjects ◽  
Increased Risk ◽  
Bidirectional Association ◽  
History Of ◽  
Incident Cases

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

scholarly journals Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 1069-1069
Author(s):  
Michael Boschmann ◽  
Stefan Engeli ◽  
Kerstin Dobberstein ◽  
Petra Budziarek ◽  
Anke Strauss ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Standardized Test ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Diabetic Patients ◽  
Lipid Mobilization ◽  
Postprandial Lipid

Abstract Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extra-pancreatic mechanisms. Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. Design: Randomized, double blind, crossover study. Setting: Academic clinical research center. Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m2. Intervention: Seven days treatment with the selective DPP-4 inhibitor vildagliptin or placebo. Standardized test meal on day seven. Main Outcome Measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin; dialysate glucose, lactate, pyruvate, glycerol. Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptine increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

scholarly journals Association between dipeptidyl peptidase-4 inhibitors and risk of bullous pemphigoid in patients with diabetes: A population-based cohort study

2020 ◽  
Author(s):  
Chen-Yi Wu ◽  
Chun-Ying Wu ◽  
Chung-Pin Li ◽  
Yiing-Jenq Chou ◽  
Yi-Hsian Lin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Bullous Pemphigoid ◽  
Cumulative Incidence ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Diabetes Diagnosis ◽  
Dipeptidyl Peptidase 4 ◽  
Duration Of Diabetes ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Diabetes Patients

Abstract Background Higher bullous pemphigoid (BP) risk has been reported to be associated with dipeptidyl peptidase 4 inhibitor (DPP4i). However, large-scale studies to investigate the association between BP and DPP4i treatment are limited. The aim of this study is to examine the association between BP risk and DPP4i treatment in diabetes patients. Methods We conducted a nationwide cohort study based on the Taiwan National Health Insurance Database between 2000 and 2015. 124,619 diabetic patients who were receiving DPP4i therapy were matched 1: 1 with diabetic patients who had never received DPP4i by age, sex, duration of diabetes, insulin usage, and propensity score-matching of comorbidities. Results Of the 124,619 diabetes patients in the two groups, the mean age at diabetes diagnosis was 52.4 ± 10.9 years, with a mean duration of diabetes of 6.0 ± 3.9 years. After adjusting for competing mortality risk, the 6-year cumulative incidence of BP in the DPP4i-treated cohort was significantly higher than that in the non-DPP4i group (0.74 per 1000; 95% confidence interval [CI]: 0.51–1.05 vs 0.38 per 1000; 95% CI: 0.26–0.53, P = .001). The DPP4i and insulin-treated group had the highest 6-year cumulative incidence for BP (0.93; 95% CI: 0.54–1.54 per 1000). Modified Cox regression analysis revealed that DPP4i treatment (HR: 2.15, 95% CI: 1.18–3.91, P = 0.01), age (HR: 1.06, P < .001), renal disease (HR: 2.32, P < .001), and metformin user (HR: 1.93, P = 0.006) were associated with increased BP risk. Conclusion DPP4i users had a 2.2-fold increase in the risk of BP, and the risk was the highest in those with concomitant use of DPP4i and insulin. The use of DPP4is as anti-diabetic medications must be monitored carefully and may be replaced by other anti-diabetic medications in BP patients.

scholarly journals Computational Analysis of Gynura bicolor Bioactive Compounds as Dipeptidyl Peptidase-IV Inhibitor

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Lina Rozano ◽  
Muhammad Redha Abdullah Zawawi ◽  
Muhamad Aizuddin Ahmad ◽  
Indu Bala Jaganath
Keyword(s):  
Binding Energy ◽  
Bioactive Compounds ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Diabetic Patients ◽  
Caffeoylquinic Acid ◽  
Dicaffeoylquinic Acid ◽  
Free Binding Energy ◽  
Gynura Bicolor

The inhibition of dipeptidyl peptidase-IV (DPPIV) is a popular route for the treatment of type-2 diabetes. Commercially available gliptin-based drugs such as sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin were specifically developed as DPPIV inhibitors for diabetic patients. The use of Gynura bicolor in treating diabetes had been reported in various in vitro experiments. However, an understanding of the inhibitory actions of G. bicolor bioactive compounds on DPPIV is still lacking and this may provide crucial information for the development of more potent and natural sources of DPPIV inhibitors. Evaluation of G. bicolor bioactive compounds for potent DPPIV inhibitors was computationally conducted using Lead IT and iGEMDOCK software, and the best free-binding energy scores for G. bicolor bioactive compounds were evaluated in comparison with the commercial DPPIV inhibitors, sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin. Drug-likeness and absorption, distribution, metabolism, and excretion (ADME) analysis were also performed. Based on molecular docking analysis, four of the identified bioactive compounds in G. bicolor, 3-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and trans-5-p-coumaroylquinic acid, resulted in lower free-binding energy scores when compared with two of the commercially available gliptin inhibitors. The results revealed that bioactive compounds in G. bicolor are potential natural inhibitors of DPPIV.

Comparison of the Effects of Mitiglinide and Glibenclamide Administered in Combination with the Dipeptidyl Peptidase-IV Inhibitor Sitagliptin in Rats with Streptozotocin-Nicotinamide-Induced Type 2 Diabetes

Drug Research ◽  
2017 ◽  
Vol 67 (07) ◽  
pp. 396-403 ◽  
Author(s):  
Kenji Akahane ◽  
Kazuma Ojima ◽  
Ayaka Yokoyama ◽  
Toshihiro Inoue ◽  
Sumiyoshi Kiguchi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Dpp Iv

Abstract We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.

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