Effects Of Dipeptidyl Peptidase-4 Inhibitors Research Articles

Effect of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcome in Diabetes Mellitus: A Systematic Review and Meta-analysis

Diabetic nephropathy is a common microvascular consequence, described by a persistent rise in albuminuria or a considerable fall in the predictable estimated glomerular filtration rate (eGFR). Dipeptidyl peptidase-4 (DPP- 4) inhibitors are frequently utilized to treat diabetes mellitus (DM), although it’s unclear how significant these drugs are in terms of specific renal outcomes (RO). This study aims to determine the impact of DPP-4 inhibitors (DPP4-I) on renal consequences in individuals with DM. The relevant studies were searched in PubMed, Google Scholar, and SciHub, and then filtered concurring to the exclusion and inclusion criteria. The preferred reporting item for systematic reviews and meta-analysis criteria were adhered to, and the extracted data were evaluated using the RevMan software. A 95% confidence interval (CI) was calculated in addition to the overall estimate measure. I-squared (I2) statistics were used to assess the studies’ heterogeneity. The qualitative evaluations of publication bias were done using the funnel plot. Ten randomized controlled studies with a total of 39,124 people were eligible for the investigation. At 24 weeks, eGFR in DM patients was not substantially affected by the DPP4-I (mean differences [MD] 4.31; 95% CI −4.93, 13.54; P < 0.00001, heterogeneity I2 = 95%; P = 0.36). Further at 52 weeks also, the changes in eGFR were found non-significant (MD 0.24 [−1.68, 2.16]) as compared to the control group (CG). The changes in urine albumin-creatinine ratio were also found non-significant as compared to the CG. The adverse events in the DPP4-I groups were also found non-significant as compared to the CG which indicates the safety of DPP4-I. Overall, more randomized clinical trials are required to confirm the exact role of DPP4-I on RO in DM.

Effect of anti-diabetic agent on interstitial lung disease in patients with diabetes mellitus.

The objective was to assess the protective role of anti-diabetic agent (ADA) in predicting interstitial lung disease (ILD) among patients with diabetes mellitus (DM). We formed a cohort of DM patients between 2009 and 2016 using data from Taiwan. Univariable and multivariable Cox proportion hazards regression models were used to examine the effect of risk factor on the risk of developing ILD, presented as a hazard ratio (HR) with a 95% confidence interval (CI). Cox proportional hazard regression analysis for the risk of DM-associated ILD with joint effect of dipeptidyl peptidase-4 inhibitor (DPP4I), glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2I) showed that SGLT2I, GLP-1 RA, and DPP-4I had a decreased risk of ILD with adjusted HR of 0.14 (0.11, 0.18), 0.29 (0.24, 0.35), and 0.64 (0.62, 0.67), respectively. DPP4I, GLP-1 RA, and SGLT2I could be considered to be introduced to this DM population for ILD risk reduction in DM, especially with SGLT2I usage.

Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus

AimsDipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM.MethodsPubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0.ResultsEleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, − 0.70, 95% CI − 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, − 4.50 pg/mL, 95% CI − 4.68 to − 4.32, P < 0.00001) when compared to placebo, and a comparable effect was demonstrated on TNF-alpha (WMD, 0.10 pg/mL, 95% CI − 0.11 to 0.30, P = 0.35) in comparison with active agents. Estimate was stable according to the sensitivity test. Subgroup analysis revealed that heterogeneity might not correlate with baseline glycated hemoglobin (HbA1c), age or treatment duration.ConclusionsA significant effect of DPP-4i on TNF-alpha levels was present in T2DM when compared to placebo. Administration of DPP-4i produced no significant effect on TNF-alpha in comparison with active comparators. Further studies with large samples should be performed to illustrate the impact of DPP-4i on TNF-alpha levels in T2DM.Trial registration International Prospective Register for Systematic Review (PROSPERO) number: CRD42020185479

Incretin-based therapy and the risk of diabetic foot ulcers and related events.

To investigate the effect of dipeptidyl peptidase-4 inhibitors (DPP4-Is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) on diabetic foot ulcer (DFU) and DFU-related outcomes (lower limb amputation [LLA], DFU-related hospitalization and mortality). We performed a cohort study with data from the Clinical Practice Research Datalink Aurum database with linkage to hospital data. We included people with type 2 diabetes starting treatment with metformin. Then we propensity score matched new users of DPP4-Is and sulphonylureas (N = 98 770), and new users of GLP1-RAs and insulin (N = 25 422). Cox proportional hazards models estimated the hazard ratios (HRs) for the outcomes. We observed a lower risk of DFU with both DPP4-I use versus sulphonylurea use (HR 0.88, 95% confidence interval [CI]: 0.79-0.97) and GLP1-RA use versus insulin use (HR 0.44, 95% CI: 0.32-0.60) for short-term exposure (≤ 400 days) and HR 0.74 (95% CI: 0.60-0.92) for long-term exposure (>400 days). Furthermore, the risks of hospitalization and mortality were lower with both DPP4-I use and GLP1-RA use. The risk of LLA was lower with GLP1-RA use. The results remained consistent across several sensitivity analyses. Incretin-based therapy was associated with a lower risk of DFU and DFU-related outcomes. This suggests benefits for the use of this treatment in people at risk of DFU.

Restoring Brain Pathways Involved in Diabetes-Associated Neurocognitive Disorders: The Potential of Dipeptidyl Peptidase 4 Inhibitors as a Therapeutic Strategy

Abstract: Diabetes, a widespread chronic metabolic disease, is projected to affect 783 million people globally by 2045. Recent studies emphasize the neuroprotective potential of dipeptidyl peptidase 4 (DPP4i) inhibitors, pointing toward a promising avenue for intervention in addressing cognitive challenges associated with diabetes. Due to limited data on the effect of DPP4i on brain pathways involved in diabetes-related neurocognitive disorders, the decision was made to conduct this study to fill existing knowledge gaps on this topic. The primary aim of our study was to evaluate the potential of DPP4 inhibitors (DPP4i) in preventing cognitive decline in mice with type 2 diabetes (T2D), placing special emphasis on gaining insight into the complex molecular mechanisms underlying this action. We examined drug efficacy in modulating neurotrophic factors, calcium levels, and the expression of key genes (HIF1α, APP, Arc) crucial for neural plasticity. Conducting cognitive assessments with the hole board and passive avoidance tests, we discerned a remarkable influence of short-term gliptin usage on the limiting progress of cognitive dysfunction in diabetic mice. The administration of DPP4 inhibitors led to heightened neurotrophin levels, increased HIF1α in the prefrontal cortex, and a significant elevation in Arc mRNA levels. Our findings reveal that DPP4 inhibitors effectively limit the progression of diabetes-related cognitive disorders. This breakthrough discovery not only opens new research avenues but also constitutes a potential starting point for creating innovative strategies for the treatment of central nervous system disorders focused on improving cognitive abilities.

Effects of dipeptidyl peptidase-4 inhibition in vivo: Dipeptidyl peptidase-4 inhibitor/gut microbiome crosstalk suggests novel therapeutic options for diabetes management.

Wang etal. report that clinical dipeptidyl peptidase-4 (DPP-4) inhibitors show little effect on microbial DPP-4 produced by Bacteroidesgenus. Furthermore, oral administration of microbial DPP-4 to high-fat diet-fed mice was found to reduce plasma active glucagon-like peptide-1 levels through an increase in extraluminal intestinal tissular DPP-4 activity, resulting in reduced glucose-induced insulin levels and exacerbated glucose tolerance.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Effect of Luseogliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, and Dipeptidyl-Peptidase 4 Inhibitors on the Quality-of-Life and Treatment Satisfaction of Patients With Type 2 Diabetes Mellitus: A Subanalysis of a Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT Study).

The effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on quality of life (QOL) and treatment satisfaction have not been directly compared. This sub-analysis of a randomized-controlled trial with an SGLT2i, luseogliflozin, and DPP-4is compared their effects on QOL and treatment satisfaction of patients. This study recruited 623 patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is. The patients were randomized into luseogliflozin or DPP-4i group and followed for 52weeks. This sub-analysis assessed QOL and treatment satisfaction using Oral Hypoglycemic Agent Questionnaire (OHA-Q) version 2 in the drug-naïve subgroup who were drug-naïve at baseline and with monotherapy with luseogliflozin or DPP-4i throughout the observation period (256 patients) at 24 and 52weeks and in the add-on subgroup who were treated with OHAs other than SGLT2is and DPP-4is (204 patients) at baseline, 24 and 52weeks. In the drug-naïve subgroup, total (50.8 ± 8.2 in luseogliflozin group and 53.1 ± 10.0 in DPP-4i group, p = 0.048) and somatic symptom scores (22.4 ± 5.0 in luseogliflozin group and 24.4 ± 5.8 in DPP-4i group, p = 0.005) at 52weeks (but not at 24weeks) were significantly higher in DPP-4i group than in luseogliflozin group. In add-on subgroup, changes in total (3.3 ± 7.8 in luseogliflozin group and 0.9 ± 7.6 in DPP-4i group, p = 0.030) and treatment convenience (1.2 ± 3.9 in luseogliflozin group and - 0.6 ± 4.2 in DPP-4i group, p = 0.002) from baseline to 24weeks (but not at 52weeks) were significantly greater in luseogliflozin group than in DPP-4i group. The QOL related to safety or glycemic control was comparable between the groups. Physicians should pay attention to side effects of SGLT2is to maintain the patients' QOL when SGLT2is are initiated or added-on. Add-on of luseogliflozin increased patients' QOL more than DPP-4is. Considering patients' QOL and treatment satisfaction is important for selecting SGLT2is or DPP-4is. UMIN000030128 and jRCTs031180241.

Anti-Inflammatory Effects of Dipeptidyl Peptidase-4 Inhibitors and Their Therapeutic Application for Parkinson's Disease

Anti-Inflammatory Effects of Dipeptidyl Peptidase-4 Inhibitors and Their Therapeutic Application for Parkinson's Disease

Effects of DPP4 Inhibitors as Neuroprotective Drug on Cognitive Impairment in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review.

Type 2 diabetes mellitus is considered as one of the risk factors for cognitive impairment. DPP4 inhibitors are effective drugs for the treatment of type 2 diabetes mellitus. However, the relationship between DPP4 inhibitors and cognitive dysfunction remains unclear. Therefore, we used a meta-analysis to determine the association between DPP4 inhibitors and cognitive impairment in type 2 diabetes mellitus. We systematically searched PubMed, CNKI, and the Cochrane Library at the time of establishment, 2022, and then made inclusion criteria and screened strategies to identify studies with more precise correlations. We included 10 studies with 5,583 participants. The data showed that DPP4 inhibitors significantly reduced the incidence rate of cognitive impairment in type 2 diabetes mellitus (SMD: 0.99; 95% CI [0.59, 1.38]). Furthermore, there was a linear correlation found between cognitive impairment in type 2 diabetes mellitus and fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. DPP4 inhibitors decreased fasting blood glucose (FPG) (SMD: 0.52; 95% CI [-0.68, -0.37]), blood glucose (2hPPG) at 2 hours after the meal (SMD: 0.82; 95% CI, [-1.2, -0.43]), and HbA1c (SMD: 0.34; 95% CI [-0.48, -0.21]). All data were statistically significant (P < 0.0001). Furthermore, we conducted subgroup analyses of the following measures at various treatment durations and ages: cognitive scores, fasting blood glucose, glycosylated hemoglobin, and two-hour postprandial blood glucose. DPP4 inhibitors significantly improved type 2 diabetic mellitus individuals' cognitive impairment and reduced fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. Subgroup analysis showed that people aged 60 to 70 years had better treatment effects at 0-180 days. This trial is registered with CRD42023399473.

The effects of dipeptidyl peptidase-4 inhibitors on cardiac structure and function using cardiac magnetic resonance: a meta-analysis of clinical studies.

The aim of the study was to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP4i) on cardiac structure and function by cardiac magnetic resonance (CMR). Research Methods & Procedures: Database including PubMed, Cochrane library, Embase and SinoMed for clinical studies of DPP4i on cardiac structure and function by CMR were searched. Two authors extracted the data and evaluated study quality independently. Mean difference (MD) or standardized MD and 95% confidence intervals (CI) were used for continuous variables. Review Manager 5.3 was used to performed the analysis. Ten references (nine studies) were included in this meta-analysis. Most of the studies were assessed as well quality by the assessment of methodological quality. For clinical control studies, the merged MD values of △LVEF by fixed-effect model and the pooled effect size in favor of DPP4i was 1.55 (95% CI 0.35 to 2.74, P=0.01). Compared with positive control drugs, DPP4i can significantly improve the LVEF (MD=4.69, 95%CI=2.70 to 6.69), but no such change compared to placebo (MD=-0.20, 95%CI=-1.69 to 1.29). For single-arm studies and partial clinical control studies that reported LVEF values before and after DPP4i treatment, random-effect model was used to combine effect size due to a large heterogeneity (Chi2 = 11.26, P=0.02, I2 = 64%), and the pooled effect size in favor of DPP4i was 2.31 (95% CI 0.01 to 4.62, P=0.05). DPP4i significantly increased the Peak filling rate (PFR) without heterogeneity when the effect sizes of two single-arm studies were combined (MD=31.98, 95% CI 13.69 to 50.27, P=0.0006; heterogeneity test: Chi2 = 0.56, P=0.46, I2 = 0%). In summary, a possible benefit of DPP4i in cardiac function (as measured by CMR) was found, both including ventricular systolic function and diastolic function.

Comparison of the efficacy of anti-diabetic medications as add-on to metformin in type 2 diabetes mellitus from a real-world database

BackgroundMetformin is recommended as a first-line drug in the guidelines of the treatment for type 2 diabetes mellitus. However, high-quality evidence from clinical trials directly comparing the degree of hypoglycemic effect of combination therapy of metformin and a hypoglycemic agent with a different mechanism of action with that of monotherapy of a hypoglycemic drug is lacking. We aimed to examine whether combination therapy of hypoglycemic agents with metformin showed antagonism, addition, or synergism compared to monotherapy with hypoglycemic agents other than metformin regarding hemoglobin A1c levels.MethodsThis retrospective cohort study used a medical information database in Japan. Non-insulin anti-hyperglycemic agents with different mechanisms of action were classified into eight drug classes. A monotherapy cohort and a combination therapy added to the metformin cohort were defined. The change in hemoglobin A1c levels was evaluated to compare the treatment effect between the cohorts.ResultsA total of 13,359 patients with type 2 diabetes mellitus in the monotherapy cohort and 1,064 in the metformin combination therapy cohort were identified. A comparison of the change from baseline HbA1c level by drug class between the two cohorts showed a similar trend. Among those treated with dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter-2 inhibitor, no clinically significant difference was observed between the two cohorts (0.00% and -0.07% for unadjusted, 0.15% and -0.03% for propensity score matching-adjusted, and 0.09% and -0.01% for inverse probability treatment weighting-adjusted analysis).ConclusionsAccording to the results of this study, the effect of dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor added to metformin seems to be additive with respect to the reduction in hemoglobin A1c.

DrugRep-HeSiaGraph: when heterogenous siamese neural network meets knowledge graphs for drug repurposing

BackgroundDrug repurposing is an approach that holds promise for identifying new therapeutic uses for existing drugs. Recently, knowledge graphs have emerged as significant tools for addressing the challenges of drug repurposing. However, there are still major issues with constructing and embedding knowledge graphs.ResultsThis study proposes a two-step method called DrugRep-HeSiaGraph to address these challenges. The method integrates the drug-disease knowledge graph with the application of a heterogeneous siamese neural network. In the first step, a drug-disease knowledge graph named DDKG-V1 is constructed by defining new relationship types, and then numerical vector representations for the nodes are created using the distributional learning method. In the second step, a heterogeneous siamese neural network called HeSiaNet is applied to enrich the embedding of drugs and diseases by bringing them closer in a new unified latent space. Then, it predicts potential drug candidates for diseases. DrugRep-HeSiaGraph achieves impressive performance metrics, including an AUC-ROC of 91.16%, an AUC-PR of 90.32%, an accuracy of 84.63%, a BS of 0.119, and an MCC of 69.31%.ConclusionWe demonstrate the effectiveness of the proposed method in identifying potential drugs for COVID-19 as a case study. In addition, this study shows the role of dipeptidyl peptidase 4 (DPP-4) as a potential receptor for SARS-CoV-2 and the effectiveness of DPP-4 inhibitors in facing COVID-19. This highlights the practical application of the model in addressing real-world challenges in the field of drug repurposing. The code and data for DrugRep-HeSiaGraph are publicly available at https://github.com/CBRC-lab/DrugRep-HeSiaGraph.

The effect of Dipeptidyl peptidase 4 (DPP-4) inhibitors on hemoglobin level in diabetic kidney disease: A retrospective cohort study.

Anemia typically develops early in the course of diabetic kidney disease (DKD). There are data to show that dipeptidyl-peptidase-4 (DPP-4) inhibitors affect hematopoietic growth factor activity and hemoglobin level. We retrospectively reviewed 443 DKD patients who were started on DDP-4 inhibitor therapy in 2019. Their hemoglobin level at baseline (6-12 months before treatment), pretreatment (0-6 months before treatment), and post-treatment periods (within 6 months after DPP-4 inhibitor), concomitant estimated glomerular filtration rate (eGFR), HbA1c, peripheral blood white cell and platelet counts were reviewed. The severity of kidney failure was classified according to the Kidney Disease: Improving Global Outcomes stages. The hemoglobin level had a small but significant decline from 11.98 ± 2.07 to 11.87 ± 2.12 g/dL from pretreatment to post-treatment period (paired Student t test, P < .0001). From the pre- to post-treatment period, the decline of hemoglobin level was 0.10 ± 0.89 g/dL, which was significantly less than that from baseline to pretreatment period (0.24 ± 0.90 g/dL, P = .0008). The change in hemoglobin level had a positive correlation with the change in HbA1c level (R = 0.218, P < .0001), but did not correlate with the type of DPP-4 inhibitor or pretreatment eGFR. There was no significant change in peripheral blood white cell or platelet count during the same period. DPP-4 inhibitor ameliorates hemoglobin decline in DKD. The effect of DPP-4 inhibitor on hemoglobin is statistically significant but clinically modest, and did not correlate with the concomitant change in kidney function.

The effect of dipeptidyl peptidase-4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center.

Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second-line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i-associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case-control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12-month follow-up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off-therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off-therapy were also noted in the DPP4i-continuance group within 12 months of follow-up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

DPP-4 Inhibitors Attenuate Fibrosis After Glaucoma Filtering Surgery by Suppressing the TGF-β/Smad Signaling Pathway.

This study investigated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on fibrosis after glaucoma filtering surgery with clinical data and an in vitro model that used transforming growth factor-β (TGF-β) to induce human Tenon's fibroblast (HTF) fibrosis. The medical records of 41 eyes of 35 patients with diabetes with neovascular glaucoma (NVG) who received initial trabeculectomy were retrospectively reviewed. The surgical success rate was compared between cases that received (n = 23) and did not receive (n = 18) DPP-4i treatment for diabetes. The antifibrotic effects of linagliptin (a DPP-4i) were evaluated with quantitative real-time PCR for fibrosis markers (α-smooth muscle actin, collagen Iα, and fibronectin), a scratch assay, and a collagen gel contraction assay of primary cultured HTFs treated with TGF-β1 and linagliptin. Western blotting analysis was performed to evaluate the levels of phosphorylated Smad2 and Smad3 in the presence of linagliptin. The Kaplan-Meier curve for bleb survival was higher in patients who received DPP-4is (P = 0.017, log-rank test). The in vitro experiments demonstrated that treatment with linagliptin attenuated the elevated levels of fibrosis markers induced by TGF-β1 in HTFs. Linagliptin treatment also prevented the migration and gel contraction of HTFs. Linagliptin inhibited the phosphorylation of Smad2 and Smad3, which is the canonical pathway of TGF-β signaling. The current study indicates the potential effect of DPP-4is for maintaining bleb function after glaucoma filtering surgery in patients with diabetes with NVG. Our results demonstrate that linagliptin attenuates fibrotic change in HTFs by inhibiting TGF-β/Smad signaling.

Effect of dipeptidyl peptidase-4 inhibitors on glycated hemoglobin levels relies on dietary sodium intake

AimsSodium load increases endogenous glucagon-like peptide-1 (GLP-1) levels in humans. Therefore, patients with an increased amount of dietary sodium intake are supposed to have higher endogenous GLP-1 levels compared to those with less dietary sodium intake. Therefore, it can be hypothesized that patients with type 2 diabetes mellitus (T2DM) with more dietary sodium intake show better dipeptidyl peptidase-4 inhibitor (DPP-4i) effect on glycemic control because of the expected higher GLP-1 level. Thus, we performed a single-center cohort study to explore this idea. MethodsMedical records of patients with T2DM prescribed DPP-4i in the last 11 years were investigated. Dietary sodium intake was measured before the DPP-4i prescription with Tanaka's formula using casual spot urine samples. The effect of DPP-4i on glycemic control was estimated by the subtraction of glycated hemoglobin (HbA1c) before DPP-4i initiation from HbA1c 1 year after DPP-4i administration. We analyzed 50 patients. ResultsDPP-4i improved HbA1c by −0.41% ± 0.66%. The effect of DPP-4i on glycemic control was significantly negatively correlated with the dietary sodium intake (r = −0.400). Thus, the more dietary sodium intake, the better the glycemic control by DPP-4i. ConclusionsThus, patients can expect better plasma glucose control by DPP-4is if patients are taking increased dietary sodium intake.

Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes: A network meta-analyses-driven approach.

The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup. The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.

Association of Dipeptidyl Peptidase-4 Inhibitors Use with Reduced Risk of Hepatocellular Carcinoma in Type 2 Diabetes Patients with Chronic HBV Infection

Previous studies have indicated that HBV infection and T2DM are the factors that increase the risk of developing HCC. The experimental evidence has shown that antiglycemic agents may reduce the risk of HCC. However, the effect of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) on the risk of HCC in T2DM patients with chronic HBV infection remains unclear. In this retrospective cohort study, we extracted patients with T2DM and chronic HBV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The cases were divided into DPP-4 inhibitors use and non-use groups, according to whether they received DPP-4 inhibitors treatment, and the risk of HCC was compared between the two groups. At the end of the follow-up, approximately 2.33% of DPP-4 inhibitors users had received an HCC diagnosis compared with 3.33% of non-DPP-4 inhibitors users (p < 0.0001). After multivariate adjustment, DPP-4 inhibitors users showed a significant reduction in HCC risk (adjusted hazard ratios (aHRs): 0.53; 95% confidence intervals (CIs): 0.44-0.65). In conclusion, this population-based retrospective cohort study indicated that, in T2DM patients with chronic HBV infection, the use of DPP-4 inhibitors significantly reduced the risk of developing HCC compared with non-DPP-4 inhibitors use.

Beneficial Effects of Dipeptidyl Peptidase-4 Inhibitors on HeartFailureWith Preserved EjectionFraction and Diabetes.

Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to exert pleiotropic effects on heart failure (HF) in animal experiments. This study sought to investigate the impact of DPP-4 inhibitors on HF patients with diabetes mellitus (DM). We analyzed hospitalized patients with HF and DM enrolled in the JROADHF (Japanese Registry Of Acute Decompensated HeartFailure) registry, a nationwide registry of acute decompensated HF. Primary exposure was the use of a DPP-4 inhibitor. The primary outcome was a composite of cardiovascular death or HF hospitalization during the median follow-up of 3.6 years according to left ventricular ejection fraction. Out of 2,999 eligible patients, 1,130 had heart failure with preserved ejection fraction (HFpEF), 572 had heart failure with midrange ejection fraction (HFmrEF), and 1,297 had heart failure with reduced ejection fraction (HFrEF). In each cohort, 444, 232, and 574 patients received a DPP-4 inhibitor, respectively. A multivariable Cox regression model showed that DPP-4 inhibitor use was associated with a lower composite of cardiovascular death or HF hospitalization in HFpEF (HR: 0.69; 95%CI: 0.55-0.87; P = 0.002) but not in HFmrEF and HFrEF. Restricted cubic spline analysis demonstrated that DPP-4 inhibitors were beneficial in patients with higher left ventricular ejection fraction. In HFpEF cohort, propensity score matching yielded 263 pairs. DPP-4 inhibitor use was associated with a lower incidence rate of the composite of cardiovascular death or HF hospitalization (19.2 vs 25.9 events per 100 patient-years; rate ratio: 0.74; 95%CI: 0.57-0.97; P = 0.027) in matched patients. DPP-4 inhibitor use was associated with better long-term outcomes in HFpEF patients with DM.