Dipeptidyl Peptidase-4 Inhibitors Research Articles

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

BACKGROUND 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. AIM To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS 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. RESULTS 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)]. CONCLUSION 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.

Enrichment and Quantitation of Dipeptidyl Peptidase IV Inhibitory Peptides in Quinoa upon Systematic Malting.

Food-derived peptides with an inhibitory effect on dipeptidyl peptidase IV (DPP-IV) can be used as an additive treatment for type 2 diabetes. The inhibitory potential of food depends on technological protein hydrolysis and gastrointestinal digestion, as the peptides only act after intestinal resorption. The effect of malting as a hydrolytic step on the availability of these peptides in grains has yet to be investigated. In this study, quinoa was malted under systematic temperature, moisture, and time variations. In the resulting malts, the DPP-IV inhibition reached a maximum of 45.02 (±10.28) %, whereas the highest overall concentration of literature-known inhibitory peptides was 4.07 μmol/L, depending on the malting parameters. After in vitro gastrointestinal digest, the inhibition of most malts, as well as the overall concentration of inhibitory peptides, could be increased significantly. Additionally, the digested malts showed higher values in both the inhibition and the peptide concentration than the unmalted quinoa. Concerning the malting parameters, germination time had the highest impact on the inhibition and the peptide concentration after digest. An analysis of the protein sizes before and after malting gave first hints toward the origin of these peptides, or their precursors, in quinoa.

Dipeptidyl Peptidase-4 Inhibitors and the Risk of Gallbladder and Bile Duct Disease Among Patients with Type 2 Diabetes: A Population-Based Cohort Study.

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors. DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17-1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease. In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year.

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data

ObjectiveTo compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice.DesignCohort study...

ASPECTS OF THE USE OF ANTIDIABETIC DRUGS IN PHARMACEUTICAL PRACTICE ON THE BASIS OF RATIONAL PHARMACOTHERAPY

The aim of the article. To study of the incidence of diabetes mellitus in Ukraine and to determine the prospects for the use and pharmaceutical development of antidiabetic drugs. Materials and methods. Data from the State Registers of Medicinal Products of Ukraine, of Wholesale and Retail Prices for Medicinal Products declared in Ukraine under an international non-proprietary or generic name (01.01.2024). Were used: systematic and comparative analysis, processing and synthesis, and generalization to determine the forecasted prospects. Results. In Ukraine the number of diabetes patients increased by 11% in the group of children and adolescents; in the group of elderly patients – by 12.5%, among the adult working – 20%, diabetes of the II type predominates. The trend of increase in the number of studies on the search for therapeutic alternatives for the treatment of type II diabetes and list of medicines on the pharmaceutical market has been revealed. In Ukraine drugs for oral use include APIs of the following pharmacological groups: sulfonylureas; meglitinides; biguanides; thiazolidinedione; α-glucosidase inhibitors; DPP-4 inhibitors; SGLT-2 inhibitors. Mechanism of action of the new class of oral hypoglycemic agents, approved by the FDA, consists in blocking SGLT-2 proteins from the proximal convoluted tubule in the kidney, leads to the prevention of reabsorption and excretion of the glucose molecule. This allows its use in combination with insulin and other antidiabetic drugs for the treatment of type I and II diabetes in patients of various age categories. According to the volume of clinical studies, SGLT-2 inhibitor SGLT-2 derivative gliflozin API drugs are the second largest group of antidiabetic drugs recommended for use by FDA and EMA regulatory bodies. Conclusions. The pharmaceutical development of mono and combined drugs with APIs SGLT-2 inhibitors gliflozin derivatives in combination with APIs with metformin, DPP-4 inhibitors, APIs thiazolidinedione derivatives is promising for solving the problem of diabetes treatment and prevention of complications for patients of different age groups including working population in Ukraine.

Glucagonlike peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors in ischemic strokes with diabetes 2.

Cardiovascular outcome trials demonstrate that glucagonlike peptide-1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes (T2D), whereas dipeptidyl peptidase-4 inhibitors (DPP-4is) have not shown cardiovascular benefits. We compared acute ischemic stroke (AIS) with T2D treated with either a GLP-1RA or DPP-4i prior to the index stroke. This national cohort study included AIS patients with T2D from 2017 to 2020 in Denmark who were users of a GLP-1RA or DPP-4i. To be categorized as a user, we required at least 12 months of exposure and no concurrent treatment with another newer glucose-lowering medication during the last 3 months prior to the index stroke. GLP-1RA users were compared to users of DPP-4i while adjusting for the calendar year of index stroke, age, sex, comorbidity, and socioeconomic factors. The study included 1567 AIS events with T2D; 593 were users of GLP-1RA and 974 of DPP-4i. The absolute risk of a very severe stroke was 2.4% (95% confidence interval [CI] = 1.2-3.7) in GLP-1RA users and 6.1% (95% CI = 4.6-7.7) in DPP-4i users. The corresponding adjusted risk ratio (aRR) of GLP-1RA versus DPP-4i was 0.49 (95% CI = 0.24-1.00). The aRRs of 30-day and 365-day mortality were 0.55 (95% CI = 0.32-0.94) and 0.72 (95% CI = 0.53-0.98), respectively. The risk of a very severe stroke as well as the 30-day and 365-day poststroke mortality rates were lower among the AIS patients with comorbid T2D receiving GLP-1RA prior to the index stroke compared to those receiving DPP-4i. Hence, GLP-1RA may improve stroke outcomes in comparison with DPP-4i.

National trends in utilisation of glucose lowering medicines by older people with diabetes in long-term care facilities

AimsTo examine national trends in glucose lowering medicine (GLM) use among older people with diabetes in long-term care facilities (LTCFs) during 2009–2019. MethodsA repeated cross-sectional study of individuals ≥65 years with diabetes in Australian LTCFs (n = 140,322) was conducted. Annual age-sex standardised prevalence of GLM use and number of defined daily doses (DDDs)/1000 resident-days were estimated. Multivariable Poisson or Negative binomial regression models were used to estimate adjusted rate ratios (aRRs) and 95 % confidence intervals (CIs). ResultsPrevalence of GLM use remained steady between 2009 (63.9%, 95 %CI 63.3–64.4) and 2019 (64.3%, 95 %CI 63.9–64.8) (aRR 1.00, 95 %CI 1.00–1.00). The percentage of residents receiving metformin increased from 36.0% (95 %CI 35.3–36.7) to 43.5% (95 %CI 42.9–44.1) (aRR 1.01, 95 %CI 1.01–1.01). Insulin use also increased from 21.5% (95 %CI 21.0–22.0) to 27.0% (95 %CI 26.5–27.5) (aRR 1.02, 95 %CI 1.02–1.02). Dipeptidyl peptidase-4 inhibitor use increased from 1.0% (95 %CI 0.9–1.1) to 21.1% (95 %CI 20.7–21.5) (aRR 1.24, 95 %CI 1.24–1.25), while sulfonylurea use decreased from 34.4% (95 %CI 33.8–35.1) to 19.3% (95 %CI 18.9–19.7) (aRR 0.93, 95 %CI 0.93–0.94). Similar trends were observed in DDDs/1000 resident days. ConclusionsThe increasing use of insulin and ongoing use of sulfonylureas suggests a need to implement evidence-based strategies to optimise diabetes care in LTCFs.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors in improvement of fatty liver index in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: A retrospective nationwide claims database study in Japan.

To date, there are limited clinical studies and real-world evidence investigating whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) are associated with improved hepatic steatosis. This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase-4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). This retrospective cohort study included new users of SGLT2i or DPP4i with T2DM and MASLD from a large claims database (JMDC Claims Database). The primary outcome was the incidence of improvement of the FLI. Cox proportional hazard models, weighted using propensity scores for predicting the initiation of treatment, were fitted to estimate hazard ratios with 95% confidence intervals (CIs). Time-course changes in the FLI values were also assessed. This study included 9127 SGLT2i and 12 286 DPP4i initiators. SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18-1.38), 1.24 (95% CI 1.13-1.37) and 1.19 (95% CI 1.05-1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow-up period. SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD. In the absence of direct head-to-head comparisons from clinical studies, our study, using real-world data, may support physicians' decision-making in clinical practice.

Empagliflozin and Risk of Incident Gout: Analysis from the EMPagliflozin Comparative Effectiveness and SafEty (EMPRISE) Cohort Study.

Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout and cardiovascular disease (CVD). Empagliflozin lowers serum urate levels by enhancing its urinary excretion. To compare initiators of empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP4i) and initiators of empagliflozin vs glucagon-like peptide-1 receptor agonist (GLP-1RA) with respect to the risk of incident gout events. Using three claims-based datasets from 08/2014 to 09/2019, we generated two cohorts (cohort 1: empagliflozin vs DPP4i; cohort 2: empagliflozin vs GLP-1RA) of adult patients with T2D and without prior history of gout or gout-specific medication dispensing separately in each dataset. To assess the risk of incident gout, we estimated hazard ratios (HR) and rate differences (RD) per 1000 person-years (PY) with their 95% confidence intervals (CI) before and after 1:1 propensity score (PS) matching adjusting for 141 baseline covariates. We identified 102,262 pairs of 1:1 propensity score-matched adults in cohort 1 and 131,216 pairs in cohort 2. Over a mean follow-up period of 8months on treatment, the risk of gout was lower in patients initiating empagliflozin compared to DPP4i (HR = 0.69: 95%CI (0.60-0.79); RD =  - 2.27: 95% CI (- 3.08, 1.46)) or GLP-1RA (HR = 0.83: 95%CI (0.73-0.94); RD =  - 0.99: 95%CI (- 1.66, - 0.32)). Results were consistent across subgroups (sex, age, body mass index, chronic kidney disease, heart failure, cardiovascular disease, and concurrent diuretic use) and sensitivity analyses. Among adults with T2D, the initiation of empagliflozin vs a DPP4i or GLP-1RA was associated with lower risk of incident gout, complementing results from a post hoc analysis of the EMPA-REG OUTCOME trial and previously published observational research focusing on the sodium-glucose co-transporter-2 inhibitor class in more narrowly defined study populations.

The impact of innovative glucose-lowering drugs on the course and outcome of COVID-19 in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus (T2DM) are at high risk of adverse outcomes in coronavirus infection (COVID-19). Despite the gradual resolution of the pandemic, new strains of the virus are emerging, characterized by high contagiousness, and the risk of infection becoming a seasonal disease is increasing. In this connection, the issue of identifying risk factors that aggravate the course of COVID-19 in patients with T2DM, including the role of initial hypoglycemic therapy, remains relevant.The review presents and systematizes up-to-date information (according to randomized clinical trials and meta-analyses) on the effect of outpatient and inpatient use of metformin and innovative hypoglycemic drugs (glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors) on the course and outcome of COVID-19 in patients with T2DM. At the same time, the potential mechanisms of the pathogenetic effect of drugs on the course of COVID-19, positive and negative aspects of their administration are described.

Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis

IntroductionStudies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease...

Combined dulaglutide-dapagliflozin treatment improves vascular dysfunction and albuminuria vs DPP4 inhibitors independently of glycaemic control

Combined dulaglutide-dapagliflozin treatment improves vascular dysfunction and albuminuria vs DPP4 inhibitors independently of glycaemic control

Analytical and Bioanalytical Methods for the Determination of Dipeptidyl Peptidase-4 Inhibitors in Various Matrices: A Comprehensive Review.

DPP-4 inhibitors, or gliptins, are new oral antidiabetic drugs for type 2 diabetes. They help to regulate insulin and glucagon. These drugs have the advantage of a lower risk of hypoglycemia compared to some other diabetes medications and are typically prescribed when metformin and sulphonylureas have become less effective. This review analyses a range of analytical and bioanalytical methods for DPP-4 inhibitors, that use spectroscopic techniques, chromatographic, and hyphenated techniques for analysis. So far, no review comprising all DPP-4 inhibitors has been presented. The primary objective of this review is to present the analysts with various analytical and bioanalytical methods for the quantification and estimation of DPP-4 inhibitors in different matrices. To improve understanding, a review was carried out by creating a database of pre-existing research from digital sources such as ScienceDirect, and PubMed. The methodology is shown in the flowchart of the literature selection process. The comprehensive assessment of methods for analysing DPP-4 inhibitors can be a valuable resource for researchers and healthcare practitioners. Hitherto, no review encompassing all DPP-4 inhibitors has been presented. Therefore, gaps in the data available on a particular subject, need to be required to collect data on a particular construct. The review suggests that chromatographic techniques were majorly used for analysis wherein solvents like acetonitrile, methanol, and buffer solutions were used as mobile phases that can deteriorate HPLC columns and equipment. So, scientists could investigate new methods for the assessment of DPP-4 inhibitors using more eco-friendly solvents.

Eosinophil-activating Semiconducting Polymer Nanoparticles for Cancer Photo-immunotherapy.

Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the development of cancer immunotherapies. We herein report an eosinophil-activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T-cell immunity for activated cancer photo-immunotherapy. SPNe is composed of an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2-cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe can generate 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe-mediated photo-immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy.

Eosinophil‐activating Semiconducting Polymer Nanoparticles for Cancer Photo‐immunotherapy

Eosinophils are important immune effector cells that affect T cell‐mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the development of cancer immunotherapies. We herein report an eosinophil‐activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T‐cell immunity for activated cancer photo‐immunotherapy. SPNe is composed of an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2‐cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe can generate 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe‐mediated photo‐immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy.

Individual dipeptidyl peptidase-4 inhibitors and acute kidney injury in patients with type 2 diabetes: A systematic review and network meta-analysis.

This network meta-analysis of randomized controlled trials aimed to determine whether any individual dipeptidyl peptidase-4 (DPP-4) inhibitors increase the risk of acute kidney injury (AKI). The Medical Literature Analysis and Retrieval System Online via PubMed, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were systematically searched to identify relevant studies. The primary outcome was AKI. A frequentist network meta-analysis was performed using a random-effects model to account for heterogeneity. Twenty-nine studies involving 56 117 participants were included. There were 918 cases of AKI (1.63%). The risk of bias was generally considered to be low. The only DPP-4 inhibitor that significantly increased the frequency of AKI when compared with placebo was sitagliptin (risk ratio 1.65, 95% confidence interval 1.22-2.23). However, because one study showed significant outliers in the funnel plot, in a highly heterogeneous population composed solely of patients undergoing surgery for coronary artery bypass graft, we conducted a post-hoc sensitivity analysis to exclude this study. The results showed no statistically significant difference in the risk of AKI between sitagliptin and placebo. Individual DPP-4 inhibitors do not appear to increase the risk of AKI. However, sitagliptin may be associated with AKI in patients with underlying severe cardiovascular disease.

Improvement of β-Cell Function After Switching From DPP-4 Inhibitors to Oral Semaglutide: SWITCH-SEMA2 Post Hoc Analysis.

Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for β-cell function is unclear. To assess the efficacy of switching from DPP-4is to oral semaglutide for β-cell function compared with DPP-4i continuation. Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups. A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for β-cell function, changes in HOMA2-β as well as DI, reflecting the ability of β-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-β [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (≥ 7 mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI. Switching to oral semaglutide ameliorated β-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and β-cells.

Risk of acute pancreatitis among new users of empagliflozin compared to sulfonylureas in patients with type 2 diabetes: A post-authorization safety study.

This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.

Role of linagliptin, a dipeptidyl peptidase-4 inhibitor against oxidative stress and neuronal damage in experimental diabetic aging brain of female rats of different age groups.

Role of linagliptin, a dipeptidyl peptidase-4 inhibitor against oxidative stress and neuronal damage in experimental diabetic aging brain of female rats of different age groups.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.