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Introduction: The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier's gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan. Methods: In this retrospective cohort study, we utilized the JMDC Claims Database. The study included patients aged 18 years or older diagnosed with type 2 diabetes mellitus, identified by a diagnostic code, who received new prescriptions for SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors between April 2014 and August 2020. Using one-to-one propensity score (PS) matching, we compared the incidence of perineal soft tissue infections, including FG, genital bacterial infection, and UTIs between groups treated with SGLT2 and DPP-4 inhibitors. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using the Cox proportional hazards model. Results: We identified 34,897 patients in the SGLT2 inhibitor group and 135,311 patients in the DPP-4 inhibitor group. After one-to-one PS matching, 31,665 pairs were generated. The mean age of the patients was 51 years, with approximately 70% being male. The use of SGLT2 inhibitors was associated with a decreased risk of UTI (HR 0.90, 95% CI 0.83–0.98) and an increased risk of genital bacterial infection (HR 1.23, 95% CI 1.03–1.46) compared to DPP-4 inhibitors. However, no significant association was observed with perineal soft tissue infection (HR 1.05, 95% CI 0.61–1.81). Conclusions: SGLT2 inhibitors were associated with a reduced risk of UTI and an increased risk of genital bacterial infection. They showed no significant association with perineal soft tissue infection when compared to DPP-4 inhibitors. Future research should explore broader demographics, focusing on the elderly and achieving gender balance, to gain a comprehensive understanding of infection risks. [ABSTRACT FROM AUTHOR]

This study explains the well-structured development and validation of the HPTLC method and the qualitative evaluation of Evogliptin in both bulk and tablet formulation using the quality by design (QbD) approach. Chromatographic separation was carried out on an aluminium-backed silica gel F254 plate using a mobile phase consisting of ethyl acetate :methanol: triethylamine (6:4:0.1 V/V/V). Densitometry was carried out at a wavelength of 267 nm. The band corresponding to the Evogliptin was obtained at Rf=0.39. The method was found to be linear, with r2=0.9961. The critical analytical attributes (CAAs) for the HPTLC method were identified. The saturation time, band length and solvent front were determined as critical method parameters (CMP) and extensively optimized employing Box-Behnken Design (BBD), with a focus on the retention factor (Rf) value as the CAA. The method described in this study exhibited linearity. The accuracy, precision, linearity, LOD, LOQ and robustness values were within the specified limits. The developed method was validated according to ICH guidelines and the results were found to be within the acceptance criteria. This study effectively demonstrates the value of the QbD approach for creating an incredibly accurate HPTLC method with improved system effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: Long-term effectiveness and durability of glucose-lowering medications are important considerations in managing type 2 diabetes (T2D). This study aimed to compare durability of treatment efficacy of once-weekly (OW) semaglutide for T2D with that of the dipeptidyl peptidase 4 inhibitor (DPP–4i) class. Methods: This observational cohort study used 2017–2022 data from the Optum® Clinformatics® Data Mart to compare long-term clinical outcomes associated with semaglutide or DPP–4i in US adults with T2D. The primary outcomes were HbA1c at 2-year follow-up, change in HbA1c from baseline, and the odds of achieving HbA1c targets. BMI at 2-year follow-up, change in BMI from baseline, odds of reducing BMI category, and the need for treatment augmentation were exploratory outcomes. Bivariate and multivariate analyses were conducted using inverse probability of treatment weighting (IPTW) weighted descriptive statistics. Results: Weighted HbA1c and BMI cohorts included 865 and 642 semaglutide users and 779 and 537 DPP–4i users, respectively. In the weighted HbA1c cohort, semaglutide and DPP–4i users had an average age of 60 years and similar baseline characteristics including HbA1c level and comorbidity status. Two-year follow-up HbA1c with semaglutide was 0.56% lower than with DPP–4i; reduction in HbA1c from baseline was 0.61% greater. Odds of achieving HbA1c level < 7% were 2.16 times greater after covariate adjustment (all, p < 0.001). Semaglutide was associated with 1.03 kg/m2 greater reduction in BMI and 2.27 times greater odds of reducing BMI category vs DPP–4i (p < 0.001). Semaglutide users were less likely to add new glucose-lowering treatment (hazard ratio [HR] 0.57; p < 0.001) or initiate insulin (HR 0.49; p < 0.001) vs DPP–4i users. Conclusion: Compared with DPP–4i, semaglutide was associated with lower follow-up HbA1c and BMI, greater reduction in HbA1c and BMI from baseline, and reduced likelihood of requiring treatment augmentation or insulin initiation to manage T2D in US adults, suggesting better durability of semaglutide vs DPP–4i. Infographic: Plain language summary: Type 2 diabetes (T2D) is a progressive disease. Over time, many patients with T2D will need multiple drugs to manage their disease. Long-term efficacy is important for achieving treatment goals, such as blood sugar control and weight loss. The amount of time that different types of diabetes drugs remain effective varies. This study used real-world data to compare two distinct types of diabetes drugs, semaglutide and dipeptidyl peptidase 4 inhibitors (DPP–4is). We looked at how blood sugar control and body weight changed with each drug after 2 years of use. We also compared how many patients needed to start using new drugs to meet their treatment goals and the odds that a patient would need to start using new drugs. Semaglutide was better than DPP–4i in reducing both blood sugar levels and body weight. Patients had over two times the odds of meeting target blood sugar levels with semaglutide. Fewer patients needed to start using new drugs with semaglutide, and patients were 43% less likely to start using new drugs to lower blood sugar than patients taking DPP–4is. [ABSTRACT FROM AUTHOR]

Objective: Impairment of immune cell signaling molecules is involved in diseases pathogenesis. The evaluation of signal transducer and activator of transcription (STAT) 4 and protein inhibitor of activated STAT (PIAS) 2 as well as immunoregulatory role of the dipeptidyl peptidase-4 inhibitor, sitagliptin were investigated in type 2 diabetes mellitus (T2DM). Materials and Methods: Peripheral blood mononuclear cells (PBMC) were purified from three study groups including healthy controls, T2DM patients with 6 months of sitagliptin treatment, and T2DM patients without sitagliptin. Expressions of STAT4 and PIAS2 were assessed with real-time polymerase chain reaction (qPCR). Results: The expression of STAT4 in patients without sitagliptin was higher than the healthy controls (p=0.001). Its expression was down- regulated in the sitagliptin treated patient group compared to those without sitagliptin (p=0.005). PIAS2 expression in patients without sitagliptin was lower than the healthy controls (p=0.009). PIAS2 was elevated in the sitagliptin treated group versus patients without sitagliptin (p=0.003). A negative correlation between STAT4 and PIAS2 was found in individuals without sitagliptin (p=0.01). In patients without sitagliptin, fasting plasma glucose was positively and negatively correlated with STAT4 and PIAS2, respectively (p=0.004 and p=0.001). Conclusion: Aberrant expression of STAT4 and reduced expression of PIAS2 were found in the T2DM patients. Sitagliptin may regulate the cell signaling pathways by elevating PIAS2 and reducing STAT4. [ABSTRACT FROM AUTHOR]

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008–2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer’s disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p

Background: Antihyperglycemic drug utilization studies are conducted frequently and describe the uptake of new drug therapies across may jurisdictions. An increasingly important, yet often absent, aspect of these studies is the impact of rurality on drug utilization. Objective(s): The objective of this study was to explore the association between place of residence (rural, urban, metropolitan) and the use of dipeptidyl peptidase 4 inhibitors (DPP-4i) for first treatment intensification of type 2 diabetes. Methods: A retrospective cohort study was conducted from April 1, 2008 to March 31, 2019 of new metformin users. A multivariable logistic regression analysis was performed to determine the association between place of residence (using postal codes) and likelihood of DPP-4i dispensing. Results: After adjusting for confounders, analysis revealed that rural-dwellers are less likely to have a DPP-4i dispensed, compared with metropolitan-dwellers (aOR:0.64; 95%CI:0.61–0.67) and over-time, the uptake in rural areas was slower. Conclusions: This study demonstrates that rurality can have an impact on drug therapy decisions at first treatment intensification, with respect to the utilization of new therapies.

Introduction: Evidence from cardiovascular outcome trials (CVOTs) for newer antidiabetic drugs is increasingly influencing revised recommendations for second-line therapy in type 2 diabetes (T2D). This systematic review aimed to compare the cost-effectiveness of newer antidiabetic drugs specified as sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), and dipeptidyl peptidase 4 inhibitor (DPP-4i) for T2D in a second-line setting. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and all relevant published studies were searched comprehensively in electronic databases, including PubMed, Embase, Web of Science, and International Health Technology Assessment database published from April 2023. The quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 reporting checklists. Results: We included 28 studies that met the inclusion criteria. Overall reporting of the identified studies largely met CHEERS 2022 recommendations. The CORE and Cardiff models were the most frequently utilized for pharmacoeconomic evaluation in T2D. Four studies consistently discovered that SGLT2i was more cost-effective than GLP-1RA in T2D who were not adequately controlled by metformin monotherapy. Four studies compared GLP-1RA with DPP-4i, sufonylurea (SU), or insulin. Except for one that demonstrated SU was cost-effective, all were GLP-1RA. Five studies revealed that SGLT2i was more cost-effective than DPP-4i or SU. Eleven studies indicated that DPP-4i was more cost-effective than traditional antidiabetic drugs. Four additional studies explored the cost-effectiveness of various antidiabetic drugs as second-line options, indicating that SU, SGLT2i, or meglitinides were more economically advantageous. The most common driven factors were the cost of new antidiabetic drugs. Conclusion: Newer antidiabetic drugs as second line are the cost-effective option for T2D from the cost-effectiveness perspective, especially SGLT2i. [ABSTRACT FROM AUTHOR]

Abstract Background Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer. Methods Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DPP4 inhibitors groups at least 8 weeks before and during ICI therapy. The primary objectives were the objective response rate (ORR) and progression‐free survival (PFS). The second objective was to evaluate the overall survival (OS) and the occurrence of immune‐related adverse events (irAEs). Results Among 466 patients, 89 (19.0%) and 377 (81%) were categorized into the MET and NMET groups, respectively. MET group had a significantly higher ORR (MET group: 24.7% vs. NMET group: 14.8%, p = 0.025) and longer PFS than those in the NMET group (MET group 5.1 month vs. NMET group 2.8 months, p = 0.018). After patients were stratified based on the prior line of therapy and PD L1 expression status, the PFS of the second‐line therapy and PD L1 ≥50 was significantly higher in the MET than in the NMET group. The proportion of patients experiencing all‐grade irAEs was numerically higher in the MET group (19.1%) than in the NMET group (14.3%), without statistical significance (p = 0.382). Conclusions Concurrent use of metformin and DPP4 inhibitors with ICIs significantly improved the clinical outcomes without increasing the incidence of irAEs in NSCLC.

The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions exacerbate each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar and endothelial dysfunction, hypercoagulation, the propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations of T2DM patients that predispose them to severe forms of COVID-19 and mortality. Severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and β-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, the most effective ways are urgently needed for countering these glucometabolic disturbances occurring during acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered candidate drugs for this purpose. This review article summarizes current knowledge regarding glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle them using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with decreased patient mortality, while DPP-4is is associated with increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in this COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed. [ABSTRACT FROM AUTHOR]

Introduction: Although not definitive, there is small increased risk of acute pancreatitis with the use of dipeptidyl peptidase 4 inhibitors (DPP4i). Hence, there is an interest in the elevation of pancreatic enzymes among type 2 diabetes mellitus (T2DM) patients using DPP4i. However, the studies regarding their association are limited and provide conflicting results. Moreover, there are no such studies among South Indian T2DM patients. Hence, we evaluated the prevalence of hyperamylasemia among South Indian T2DM patients and its association with DPP4i use. Methods: This cross-sectional study was conducted at a tertiary health care center from South India. Adult T2DM patients on stable doses of antidiabetic medications for at least previous 3 months were included in the study. Patients with other types of diabetes mellitus, gall stones, diabetic ketoacidosis, acute illness, chronic kidney disease and untreated hypothyroidism were excluded from the study. All participants were evaluated with glycemic parameters, serum creatinine and serum amylase. Hyperamylasemia was defined as serum amylase ≥220 U/L. Results: A total of 200 participants were included in the study among whom 93 patients were not on DPP4i whereas 107 were on DPP4i including 41 (38.32%) each on teneligliptin and sitagliptin. Baseline characteristics including glycemic measures were comparable between DPP4i users and nonusers. A total of 14 patients (7%) had hyperamylasemia but the prevalence of hyperamylasemia did not differ between DPP4i users and nonuser (6/107 vs. 8/93, P = 0.42). Conclusions: Asymptomatic hyperamylasemia is not uncommon in South Indian T2DM patients but is not associated with the use of DPP4i. [ABSTRACT FROM AUTHOR]

Background/Aims We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). Methods An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. Results DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. Conclusions The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

Abstract Background Dipeptidyl peptidase 4 inhibitor (DPP4i) is an effective medicine for type 2 diabetes mellitus (T2DM). Some articles reported DPP4i improves insulin secretion and insulin resistance. However, these effects are not well established by glucose clamp test and test meal in Japanese. We investigated the effect of DPP4i on insulin resistance and insulin secretion by using the glucose clamp test and meal tolerance test (MTT). Methods We performed a MTT, and the hyperinsulinemic-euglycemic clamp in 8 Japanese patients with T2DM. This study was a single-arm study. We measured fasting and postprandial glucose, insulin, incretins, and glucagon levels. We also measured serum adiponectin levels. Results HbA1c was significantly decreased after 3 months. The fasting and postprandial glucose levels were significantly decreased. Fasting and postprandial insulin levels were not changed. The insulin resistance derived from the glucose clamp test was significantly improved. HOMA-IR was not significantly changed. GLP-1 and GIP were significantly increased but glucagon did not change. Adiponectin was not significantly changed. Conclusions Although the number of patients was very small, these results suggested that DPP4i treatment might improve insulin resistance without changing insulin secretion.

Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into "classically activated macrophages" (M1) and "alternatively activated macrophages" (M2). The present study investigated and compared the conventional fluid therapy vs Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups (n = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-a (TNF-a), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI +Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline +Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that dipeptidyl peptidase 4 (DPP4) inhibitors increase the risk of development of bullous pemphigoid (BP), which is the most common autoimmune blistering skin disease; however, the associated mechanisms remain unclear, and thus far, no therapeutic targets responsible for drug-induced BP have been identified. Therefore, we used clinical data mining to identify candidate drugs that can suppress DPP4 inhibitor-associated BP, and we experimentally examined the underlying molecular mechanisms using human peripheral blood mononuclear cells (hPBMCs). A search of the US Food and Drug Administration Adverse Event Reporting System and the IBM® MarketScan® Research databases indicated that DPP4 inhibitors increased the risk of BP, and that the concomitant use of lisinopril, an angiotensin-converting enzyme inhibitor, significantly decreased the incidence of BP in patients receiving DPP4 inhibitors. Additionally, in vitro experiments with hPBMCs showed that DPP4 inhibitors upregulated mRNA expression of MMP9 and ACE2, which are responsible for the pathophysiology of BP in monocytes/ macrophages. Furthermore, lisinopril and Mas receptor (MasR) inhibitors suppressed DPP4 inhibitor-induced upregulation of MMP9. These findings suggest that the modulation of the renin-angiotensin system, especially the angiotensin1-7/MasR axis, is a therapeutic target in DPP4 inhibitorassociated BP. [ABSTRACT FROM AUTHOR]

Background: Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer. Methods: Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DPP4 inhibitors groups at least 8 weeks before and during ICI therapy. The primary objectives were the objective response rate (ORR) and progression‐free survival (PFS). The second objective was to evaluate the overall survival (OS) and the occurrence of immune‐related adverse events (irAEs). Results: Among 466 patients, 89 (19.0%) and 377 (81%) were categorized into the MET and NMET groups, respectively. MET group had a significantly higher ORR (MET group: 24.7% vs. NMET group: 14.8%, p = 0.025) and longer PFS than those in the NMET group (MET group 5.1 month vs. NMET group 2.8 months, p = 0.018). After patients were stratified based on the prior line of therapy and PD L1 expression status, the PFS of the second‐line therapy and PD L1 ≥50 was significantly higher in the MET than in the NMET group. The proportion of patients experiencing all‐grade irAEs was numerically higher in the MET group (19.1%) than in the NMET group (14.3%), without statistical significance (p = 0.382). Conclusions: Concurrent use of metformin and DPP4 inhibitors with ICIs significantly improved the clinical outcomes without increasing the incidence of irAEs in NSCLC. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into “classically activated macrophages” (M1) and “alternatively activated macrophages” (M2). The present study investigated and compared the conventional fluid therapy vs Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups (n = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-α (TNF-α), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI+Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline+Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway.

Purpose: We evaluated the pharmacokinetics, safety, and tolerability of a fixed-dose combination (FDC) of dapagliflozin/sitagliptin versus individual component (IC) tablets in healthy Western and Korean participants. The combination of these antihyperglycemic drugs provides efficient glucose control, and the use of FDC has generally been shown to improve medication adherence in individuals with type 2 diabetes mellitus (T2DM)., Methods: Two randomized, open-label, two-period, two-treatment, single-dose, single-center, crossover bioequivalence studies conducted on healthy fasted German participants (aged 18-55 years; Western study) and South Korean participants (aged 19-55 years; Korean study) were included. In both studies, pharmacokinetic parameters (maximum [peak] plasma concentration [C max ], area under the plasma concentration-time curve from zero to the last quantifiable concentration [AUC last ], and area under the plasma concentration-time curve from zero to infinity [AUC inf ]) were used to assess the bioequivalence of 10 mg dapagliflozin/100 mg sitagliptin FDC (Treatment A) with their ICs (Treatment B) under fasted conditions. Safety and tolerability were assessed throughout the study., Findings: Forty-six healthy participants (male, 60.9%; mean age, 39.5 years; mean body mass index [BMI], 23.9 kg/m 2 ) were randomized in the Western study, and 51 healthy participants (male, 100.0%; mean age, 24.6 years; mean BMI, 23.9 kg/m 2 ) were randomized in the Korean study. In both studies, the participants were randomized 1:1 into treatment sequence AB and treatment sequence BA. Dapagliflozin/sitagliptin FDC was bioequivalent to IC tablets in both Western and Korean studies, as the 90% confidence interval of the FDC to IC ratios of the geometric least-squares means of the pharmacokinetic parameters for both dapagliflozin and sitagliptin was within the 0.8000-1.2500 bioequivalence criterion limit. The observed differences in pharmacokinetic parameters, such as C max , AUC last , and AUC inf , between the Western and Korean studies were not clinically meaningful. Dapagliflozin/sitagliptin FDC and their ICs were well tolerated, with no serious adverse events reported in any of the study populations., Implications: The 10 mg dapagliflozin/100 mg sitagliptin FDC and IC formulations were bioequivalent in fasted healthy Western and Korean participants, with no new safety concerns identified, thus offering a useful alternative for patients currently receiving individual medications as part of their treatment regimen., Clinical Trial Registration: Western study (clinicaltrials.gov: NCT05266404) and Korean study (clinicaltrials.gov: NCT05453786)., Competing Interests: Declaration of competing interests Dr Lukka, Dr Tang, Dr Hammarstedt, Dr Conrad, Ms Heijer, Dr Karlsson, and Dr Boulton are employees of AstraZeneca. Dr Lukka, Dr Tang, Dr Hammarstedt, Ms Heijer, Dr Karlsson, and Dr Boulton own AstraZeneca stock., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dipeptidyl peptidase 4 inhibitor (DPP4i) is an effective medicine for type 2 diabetes mellitus (T2DM). Some articles reported DPP4i improves insulin secretion and insulin resistance. However, these effects are not well established by glucose clamp test and test meal in Japanese. We investigated the effect of DPP4i on insulin resistance and insulin secretion by using the glucose clamp test and meal tolerance test (MTT). Methods: We performed a MTT, and the hyperinsulinemic-euglycemic clamp in 8 Japanese patients with T2DM. This study was a single-arm study. We measured fasting and postprandial glucose, insulin, incretins, and glucagon levels. We also measured serum adiponectin levels. Results: HbA1c was significantly decreased after 3 months. The fasting and postprandial glucose levels were significantly decreased. Fasting and postprandial insulin levels were not changed. The insulin resistance derived from the glucose clamp test was significantly improved. HOMA-IR was not significantly changed. GLP-1 and GIP were significantly increased but glucagon did not change. Adiponectin was not significantly changed. Conclusions: Although the number of patients was very small, these results suggested that DPP4i treatment might improve insulin resistance without changing insulin secretion. [ABSTRACT FROM AUTHOR]

Introduction: Vildagliptin and metformin are two well-established oral antidiabetics with a complementary mechanism of action. Two new generic products, vildagliptin and its fixed-drug combination (FDC) with metformin, were tested for bioequivalence versus the approved originator reference products (Galvus® and Eucreas®). Methods: Three randomized studies with two-treatment, two-period, two-sequence crossover design were conducted in healthy adults. One study evaluated vildagliptin 50 mg tablets as single dose under fasting conditions. Vildagliptin–metformin FDC tablet strengths of 50/850 mg and 50/1000 mg were evaluated in separate studies as single dose under fed conditions, given 30 min after a standardized high-fat, high-calorie breakfast following 10 h overnight fasting. Blood samples for analysis were collected until 24 h after dosing in each study period. Bioequivalence between test (T) and reference (R) products required 90% confidence interval (CIs) for the geometric least square (LS) mean T/R ratio to be within 80–125% for the pharmacokinetic parameters, maximum plasma concentration (Cmax), and area under the curve (AUC0–t). Results: The 90% CIs of geometric LS means of T/R ratio for Cmax and AUC0–t with vildagliptin tablets of 50 mg were 92.22–103.94% and 99.00–102.66%, respectively; corresponding results with FDC tablets for 50/850 mg tablets were 94.81–115.41% and 95.28–106.00% for vildagliptin and 90.87–101.18% and 90.56–100.09% for metformin; for 50/1000 mg tablets Cmax and AUC0–t were 105.56–122.30% and 98.30–107.55%, respectively, for vildagliptin and 92.14–103.73% and 94.60–101.81%, respectively, for metformin. Other parameters such as AUC0–∞, time to maximum concentration (Tmax), and terminal half-life (t1/2) were comparable between test and reference products. Adverse events (AEs), mainly vomiting, were reported without relevant difference between test and reference products in each study. AEs were generally mild and transient. No severe or serious AEs occurred. Conclusions: The new generic drug products of vildagliptin and the FDCs of vildagliptin and metformin demonstrated bioequivalence to the approved originator products and are therefore expected to provide similar therapeutic effects. [ABSTRACT FROM AUTHOR]

Eugene Han,1 Minyoung Lee,2 Yong-ho Lee,2– 4 Hye Soon Kim,1 Byung-wan Lee,2– 4 Bong-Soo Cha,2– 4 Eun Seok Kang2– 4 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea; 4Severance Hospital Diabetes Center, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Eun Seok KangDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of KoreaTel +82 2 2228 1938Fax +82 2 393 6884Email edgo@yuhs.acIntroduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for type 2 diabetes (T2D) and their glycemic control effects are well studied. However, information regarding the effects of switching DPP-4 inhibitors is limited, especially in older patients.Research Design and Methods: We investigated whether switching from linagliptin to teneligliptin decreases blood glucose in older (≥ 65 years) T2D patients. In total, 164 patients with T2D who switched from linagliptin to teneligliptin for > 12 weeks were included and the primary outcome was glycemic changes.Results: Switching from linagliptin to teneligliptin ameliorated fasting blood glucose (148.1 ± 47.1 to 139.6 ± 43.4 mg/dL), glycated hemoglobin (HbA1c; 7.9 ± 1.3 to 7.5 ± 1.2%), and postprandial blood glucose (224.8 ± 77.4 to 205.8 ± 70.8 mg/dL) levels (all P < 0.05). Low-density lipoprotein cholesterol concentration was reduced while liver and kidney functions were maintained. Subgroup analysis showed that glucose control improved more in patients with uncontrolled hyperglycemia (HbA1c > 8.0%) and chronic kidney disease (estimated glomerular filtration rate < 90 mL/min/1.73m2). Multiple logistic analysis indicated higher baseline HbA1c was the strongest predictor of teneligliptin switching response.Conclusion: Switching from linagliptin to teneligliptin helps maintain kidney function and reduce blood glucose safely in older patients with T2D.Keywords: dipeptidyl peptidase 4 inhibitor, linagliptin, teneligliptin, type 2 diabetes mellitus, older patients, chronic kidney disease

Lin Chen,1,* Xiujuan Zhang,2,* Li Zhang,3 Dongmei Zheng2 1Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongmei ZhengDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, People’s Republic of ChinaTel + 86 531 68776375Email zhengdongmei1971@163.comBackground and Aim: Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of chronic liver disease characterized by aberrant accumulation of triglycerides (TG) in hepatocytes without excessive alcohol consumption. Hepatic lipotoxicity derived from overaccumulation of free fatty acids is considered as one of the typical hallmarks of NAFLD. Insulin resistance (IR) and chronic inflammation are widely recognized as the key etiological factors associated with NAFLD. Dipeptidyl peptidase 4 inhibitor (DPP4i) is a novel pharmacological agent extensively applied in the treatment of Type 2 Diabetes Mellitus (T2DM) for decades which also have a liver protective effect.Methods: In order to invest the therapeutic efficiency and underlying mechanism of DPP4i saxagliptin, we used high-fat diet (HFD) and streptozotocin-induced NAFLD treated with saxagliptin. Biochemical, histomorphological, genetic and protein expression of related pathways were investigated.Results: Fasting blood glucose (FBG), TG, total cholesterol (TC), and low-density lipoprotein cholesterin significantly increased in NAFLD group, which also exhibited severe steatosis. Other remarkable findings were hyperinsulinemia, increased DPP4, PTP-1B and TNF-α level and decreased GLP-1, ACOX-1, CPT-1A expression, concomitant with liver DPP4 expression enhancement and serum DPP4 elevation. These undesirable consequences were alleviated by saxagliptin to a certain degree.Conclusion: DPP4i saxagliptin improves NAFLD by ameliorating IR, inflammation, downregulation of hepatic DPP4 and sDPP4, as well as subsequent steatosis. The elevation of hepatic DPP4 and sDPP4 and succedent post-treatment decrease suggested that DPP4 may involve in the development of NAFLD. The anti-lipotoxic effect of DPP4i may involve the activation of CPT1A and ACOX1 related β-oxidation signaling pathway suppression of TNF-α mediated inflammatory and PTP-1B. The results covered in this article showed that saxagliptin affects many aspects of the pathological characteristics of NAFLD, suggesting that DPP4i saxagliptin may offer a novel therapeutic option for NAFLD.Keywords: dipeptidyl peptidase 4 inhibitor DPP4i, non-alcoholic fatty liver disease NAFLD, inflammation, insulin resistance IR

Alogliptin, a dipeptidylpeptidase-4 inhibitor, is an oral hypoglycemic agent approved in many countries for the treatment of patients with type 2 diabetes, including the United States, Europe, and Japan. The drug is effective both as a monotherapy, and as an additional or combined treatment of type 2 diabetes. Alogliptin is well tolerated by patients, including the elderly, as well as those suffering from kidney and / or liver failure or having a high risk of cardiovascular events. The low risk of hypoglycemia, weight gain, acute pancreatitis, and side gastrointestinal events. During treatment with alogliptin has been demonstrated in both long-term (up to 4.5 years) studies and in actual clinical practice. Alogliptin increases postprandial levels of the glucagon-like peptide-1, which leads to insulin secretion and normalization of glucose homeostasis. Treatment with alogliptin is associated not only with improved glucose metabolism, but also with a decrease in blood pressure and arterial rigidity in patients with arterial hypertension and diabetes, as well as normalizing the lipid profile. In patients with diabetes mellitus who have recently undergone acute coronary syndrome and received alogliptin, the frequency of serious adverse cardiovascular events does not increase. Experimental data show that alogliptin reduces ventricular hypertrophy, interstitial fibrosis, and diastolic dysfunction. Alogliptin has a number of unique properties. It is assumed that it can increase the number of circulating endothelial progenitor cells that play an important role in endothelial repair and neovascularization. Alogliptin preserves the functionality and structure of the mitochondria of cardiomyocytes. The drug may be a potential treatment for patients with MODY1 diabetes at an early stage of the disease, when residual insulin secretion is preserved. Treatment with a fixed combination of Alogliptin + Metformin results in better glycemic control than monotherapy and is well tolerated. There is evidence that treatment with alogliptin is not associated with an increased risk of pancreatitis or pancreatic cancer.

Background: Antihyperglycemic drug utilization studies are conducted frequently and describe the uptake of new drug therapies across may jurisdictions. An increasingly important, yet often absent, aspect of these studies is the impact of rurality on drug utilization., Objectives: The objective of this study was to explore the association between place of residence (rural, urban, metropolitan) and the use of dipeptidyl peptidase 4 inhibitors (DPP-4i) for first treatment intensification of type 2 diabetes., Methods: A retrospective cohort study was conducted from April 1, 2008 to March 31, 2019 of new metformin users. A multivariable logistic regression analysis was performed to determine the association between place of residence (using postal codes) and likelihood of DPP-4i dispensing., Results: After adjusting for confounders, analysis revealed that rural-dwellers are less likely to have a DPP-4i dispensed, compared with metropolitan-dwellers (aOR:0.64; 95%CI:0.61-0.67) and over-time, the uptake in rural areas was slower., Conclusions: This study demonstrates that rurality can have an impact on drug therapy decisions at first treatment intensification, with respect to the utilization of new therapies., Competing Interests: No potential conflicts of interest relevant to this article were reported. S.H.S. is supported as the Chair in Patient Health Management, jointly held by the Faculty of Pharmacy and Pharmaceutical Sciences and Faculty of Medicine and Dentistry, University of Alberta. This study is based in part on data provided by Alberta Health. The interpretation and conclusions contained herein are those of the researchers and do not necessarily represent the views of the Government of Alberta. Neither the Government of Alberta nor Alberta Health express any opinion in relation to this study., (© 2024 The Authors.)

Introduction: No study has compared the effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) on patients' quality-of-life (QOL). Methods: We enrolled 253 drug-naïve Japanese patients with type 2 diabetes mellitus (T2DM), randomly assigned them into a dapagliflozin (SGLT2i) group or DPP4i group in approximately 1:1 ratio, and monitored them for 24 weeks. The primary endpoint was the proportion of subjects indicating improvement in the "overall quality of life" domain of SHIELD-WQ-9 at week 24. Secondary endpoints included other domains of SHIELD-WQ-9, DTR-QOL, EQ-5D-5L, medication preference, medication adherence, diet therapy adherence, body weight, body mass index (BMI), abdominal circumference, HbA1c, and frequency of adverse events. Results: The proportion of subjects indicating improvement in the "overall quality of life" domain of SHIELD-WQ-9 at week 24 was higher in the dapagliflozin group (28.4%) than in the DPP4i group (18.6%) (p = 0.08). The proportion of subjects indicating improvement in the "physical health" domain of SHIELD-WQ-9 at week 24 was significantly higher in the dapagliflozin group (42.2%) than in the DPP4i group (23.7%) (p = 0.004). Total scores and domain 1 scores of DTR-QOL showed greater improvement in the dapagliflozin group (14.3 ± 15.6 and 15.5 ± 20.8, respectively) than in the DPP4i group (10.2 ± 15.6 and 10.3 ± 19.5, respectively) (both p = 0.05). EQ-5D-5L scores had significantly improved in the DPP4i group (0.023 ± 0.088) (p = 0.005); the intergroup difference was not significant (p = 0.14). Body weight (p < 0.001), BMI (p < 0.001), and abdominal circumference (p = 0.019) had significantly decreased in the dapagliflozin group compared with the corresponding values in the DPP4i group. Conclusion: Dapagliflozin showed a comparable or more favorable benefit on Japanese patients' QOL compared with DPP4is. Dapagliflozin was well tolerated. It significantly reduced body weight, which was significantly correlated with improvement in the patients' QOL. This study demonstrates that dapagliflozin can be used as a first-line drug for T2DM in Japan with a beneficial impact on patients' QOL. Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN000030514); Japan Registry of Clinical Trials (jRCTs051180165). [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the efficacy and safety of dipeptidyl peptidase 4 inhibitors (DPP4i) used in combination with insulin in patients with type 2 diabetes mellitus (T2DM). Methods: We searched the MEDLINE, Embase, and Cochrane library databases for randomized controlled trials (RCTs) published through June 2018. Studies with at least a 12-week treatment period were included to compare the addition of DPP4i to insulin with insulin control therapy. Meanwhile, groups on a stable insulin dosage (insulin-stable subgroup) or titrating insulin dosage (insulin-flexible subgroup) were analyzed separately. Results: Twenty-one RCTs with 3697 patients randomized to a DPP4i/insulin treatment arm and 3538 to an insulin control arm were included. DPP4i, when added to insulin therapy, led to a significantly greater reduction in HbA1c (− 0.57%, 95% CI − 0.66, − 0.48) and provided significantly greater odds of achieving the HbA1c target < 7% (OR 3.45; 95% CI 2.58, 4.63). These effects were achieved in the context of a decrease in the daily insulin requirement, without increases in hypoglycemia risk and body weight, compared with the control treatment. Subgroup analysis showed control-adjusted reductions in HbA1c from baseline in the insulin-stable subgroup (− 0.64%; 95% CI − 0.74, − 0.53) and the insulin-flexible subgroup (− 0.43%; 95% CI − 0.56, − 0.30). Other results occurred similarly in both subgroups. Conclusions: The addition of DPP4i to insulin is associated with a statistically significant reduction in glycemic control as measured by HbA1c, fasting plasma glucose, and 2-h postprandial glucose, without increasing the risk of hypoglycemia and weight gain. These conclusions were also observed in both stable-dose and flexible-dose insulin subgroups. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effect of anagliptin (Ana), a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, on acute ischemia‐induced bladder dysfunction in rats. Methods: Eight‐week‐old female Wistar‐ST rats were randomly assigned into four groups: (a) sham; (b) ligation (Lig); (c) Lig + Ana; and (d) Lig + Liraglutide (a glucagon‐like peptide‐1 [GLP‐1] receptor agonist; Lira). Rats in the Lig, Lig + Ana, and Lig + Lira groups underwent ligature of the bilateral internal iliac arteries. Ana was orally administered mixed with the CE‐2 diet. Lira was subcutaneously administered once a day. Blood glucose levels, plasma dipeptidyl peptidase 4 (DPP‐4) activity, GLP‐1 levels, and bladder function were measured in all groups. Bladder blood flow was measured in the sham, Lig, and Lig + Ana groups, 4 weeks postsurgery. Results: No differences in blood glucose levels among the groups were observed. DPP‐4 activity decreased in the Lig + Ana group (P <.01). GLP‐1 levels in the Lig + Ana and Lig + Lira groups were higher than those in the sham and Lig groups (P <.01). Intercontraction intervals (ICIs) were longer in the Lig and Lig + Lira groups than in the sham group (P <.05), but similar to those observed in the Lig + Ana and sham groups. The Lig group exhibited reduced bladder blood flow relative to the sham group (P <.01); however, this measure improved in the Lig + Ana group (P <.01). Conclusions: Ana administration improved ICIs and bladder blood flow after acute bladder ischemia through a GLP‐1 receptor‐independent signaling pathway, without altering the blood glucose levels. Therefore, Ana dosing might be useful to prevent ischemia‐induced bladder dysfunctions. [ABSTRACT FROM AUTHOR]

Introduction: Metformin is the recommended initial treatment in type 2 diabetes mellitus (T2DM), but when this does not give adequate glucose control the choice of which second-line drug to use is uncertain as none have been found to have a better overall glycaemic response. In this real-world study dipeptidyl peptidase 4 inhibitors (DPP4i), sulphonylureas (SU), thiazolidinediones (TZD) and sodium glucose co-transporter 2 inhibitors (SGLT2i) were compared for their effectiveness in lowering glycated haemoglobin (HbA1c) levels for a particular individual based on their clinical characteristics. Methods: A retrospective analysis was undertaken of electronic health records of people with T2DM prescribed metformin alongside a DPP4i, SU, TZD or SGLT2i at second-line. Regression modelling was used to model the changes in HbA1c from baseline at month 6 and month 12 for the individual therapies, adjusting for demographic and clinical characteristics. Results: There were 7170 people included in the study. Treatment at second-line with SUs, DPP4i, TZDs and SGLT2i resulted in similar percentages of people achieving the recommended HbA1c target of < 7.5% (58 mmol/mol) at both 6 and 12 months. For those receiving SGLT2i and SUs, the greatest improvement in HbA1c was observed in relatively younger and older people, respectively. Trends were detected between other baseline characteristics and HbA1c improvement by drug class, but they were not statistically significant. Non-adherence rates were low for all drug classes. People with a higher medication possession ratio (≥ 80%) also had greater improvements in HbA1c at 12 months. Conclusion: This study identified patients' phenotypic characteristics that may have the potential to influence individual treatment response. Accounting for these characteristics in clinical treatment decisions may facilitate individualised prescribing by being able to select the right drug for the right patient. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for ASCVD, the aim of this study was to investigate the effects of a dipeptidyl peptidase-4 inhibitor, sitagliptin, on prevention of progression of coronary atherosclerosis assessed by three-dimensional quantitative coronary angiography (3D-QCA) in T2DM patients with coronary artery disease (CAD). This was a prospective, randomized, double-center, open-label, blinded end point, controlled 18-month study in patients with CAD and T2DM. A total of 149 patients, who had at least 1 atherosclerotic plaque with 20%–80% luminal narrowing in a coronary artery, and had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention, were randomized to sitagliptin group (n = 74) or control group (n = 75). Atherosclerosis progression was measured by repeat 3D-QCA examination in 88 patients at study completion. The primary outcome was changes in percent atheroma volume (PAV) from baseline to study completion measured by 3D-QCA. Secondary outcomes included change in 3D-QCA-derived total atheroma volume (TAV) and late lumen loss (LLL). The primary outcome of PAV increased of 1.69% (95%CL, −0.8%–4.2%) with sitagliptin and 5.12% (95%CL, 3.49%–6.74%) with the conventional treatment (p = 0.023). The secondary outcome of change in TAV in patients treated with sitagliptin increased of 6.45 mm3 (95%CL,-2.46 to 6.36 mm3) and 9.45 mm3 (95%CL,-4.52 to 10.14 mm3) with conventional treatment (p = 0.023), however, no significant difference between groups was observed (p = 0.175). Patients treated with sitagliptin had similar LLL as compared with conventional antidiabetics (−0.06, 95%CL, −0.22 to 0.03 vs. −0.08, −0.23 to −0.03 mm, p = 0.689). In patients with type 2 diabetes and coronary artery disease, treatment with sitagliptin resulted in a significantly lower rate of progression of coronary atherosclerosis compared with conventional treatment. Image 1 • Sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, have anti-atherogenic effects both in an animal model and clinical setting. • At 18 months, sitagliptin attenuated the progression of coronary atherosclerosis in patients with coronary disease and type 2 diabetes independent of the effect on glycaemic control evaluated with three-dimension quantitative coronary angiography (3D-QCA) analysis. • This study may have important implications for defining the optimal strategy for management of patients with type 2 diabetes and coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Teneligliptin, a dipeptidyl peptidase 4 inhibitor, was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan in 2012. However, clinical trials of teneligliptin involved limited numbers of elderly patients. Therefore, we investigated the safety and efficacy of teneligliptin in elderly patients with T2DM.Methods: This 3-year follow-up RUBY surveillance registered patients with T2DM who started treatment with teneligliptin between May 2013 and February 2015 in Japan. Collected data included demographics, treatments, adverse drug reactions (ADRs), and laboratory variables. Data were analysed for patients in three age subgroups (< 65, ≥ 65 to < 75, or ≥ 75 years old). Safety was assessed as the incidence of ADRs and efficacy was assessed in terms of glycaemic control, for up to 3 years.Results: The ADRs and serious ADRs occurred in 3.35% and 0.65% of 4596 patients aged < 65 years, in 4.42% and 1.22% of 3371 patients aged ≥ 65 to < 75 years, and in 3.99% and 1.69% of 2729 patients aged ≥ 75 years. The most common ADRs in patients aged ≥ 65 to < 75 years and ≥ 75 years were gastrointestinal disorders, but the incidence of these ADRs did not show an age-dependent increase. Hypoglycaemia occurred in 0.24%, 0.56%, and 0.29% of patients in each age subgroup, respectively. The least-squares mean changes in glycosylated haemoglobin (HbA1c) adjusted for baseline were - 0.66 ± 0.02% (n = 2177), - 0.72 ± 0.02% (n = 1689), and - 0.77 ± 0.03% (n = 1161) at 3 years.Conclusion: There was no clear difference in the number of ADRs among the three age subgroups, although the incidence of serious ADRs was higher in elderly patients than in patients aged < 65 years. We found no additional safety or efficacy concerns among elderly patients beyond those already described in the package insert. The present results support the use of teneligliptin in elderly patients with T2DM in real-world clinical practice.Trial Registration: Japic Clinical Trials Information identifier, Japic CTI-153047. [ABSTRACT FROM AUTHOR]

Introduction: Teneligliptin is a dipeptidyl peptidase 4 inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan in 2012. We performed a long-term post-marketing surveillance (RUBY) to obtain real-world evidence regarding the safety and efficacy of teneligliptin in Japan.Methods: This 3-year follow-up RUBY surveillance registered patients with T2DM who started treatment with teneligliptin between May 2013 and February 2015 in Japan. Collected data included demographics, treatments, adverse drug reactions (ADRs) and laboratory variables. Data were evaluated in all patients and in patients divided according to baseline renal function across categories of estimated glomerular filtration rate (G1-G5) and dialysis. Safety was assessed as the incidence of ADRs and efficacy was assessed in terms of glycaemic control, for up to 3 years.Results: Of 11,677 patients registered, 10,696 and 10,249 were evaluable for safety and efficacy analyses, respectively. The median duration of exposure was 1096 days. ADRs occurred in 412 patients (3.85%) and were serious in 117 patients (1.09%). The most frequent ADR class was gastrointestinal disorders (0.68%), which included constipation. There were no new ADRs warranting attention beyond those already described in teneligliptin's package insert. ADRs and serious ADRs in renal function subgroups occurred in 3.24-7.14% and 0.65-5.36% in G1-G5, and 4.49% and 1.92% in patients on dialysis, respectively. Reduction in HbA1c was sustained for 3 years after starting teneligliptin (- 0.70% ± 1.36%, p < 0.001 at 3 years). The least-squares mean changes in HbA1c adjusted for baseline were - 0.76% to - 0.66% in G1-G5 at 3 years. Glycated albumin levels decreased in patients on dialysis (- 2.92% ± 4.78% at 3 years).Conclusion: There were no new safety or efficacy concerns about teneligliptin used in long-term, real-world, clinical settings in patients with T2DM with any stages of renal impairment.Trial Registration: Japan Pharmaceutical Information Center clinical trials database identifier: Japic CTI-153047. Plain language summary available for this article. [ABSTRACT FROM AUTHOR]

Background and Objectives: Myocarditis is a potentially fatal disease, but curative treatments have not yet been established. Myocardial inflammation is an important pathogenesis of this disease, and immunosuppressants such as methylprednisolone and immunoglobulin have been used for treatment; however, the effectiveness needs to be improved. Thalidomide and dipeptidyl peptidase (DPP) 4 inhibitors were recently investigated regarding their immunomodulatory properties. This study aimed to test whether thalidomide or a DPP4 inhibitor (evogliptin) can improve the effectiveness of myocarditis treatment using a rat model of experimental autoimmune myocarditis (EAM)., Methods: Rats with or without myocarditis were administered thalidomide at 100 mg/kg/day and DPP4 inhibitor at 10 mg/kg/day orally. Measurement of echocardiography, serum inflammatory cytokines, myocardial histopathological examination, and immunohistochemical staining for leukocytes, macrophages, CD4+ T cells, and cytoskeleton were performed after 3 weeks, and the fibrosis area was measured after 3 and 6 weeks., Results: Thalidomide and DPP4 inhibitor did not reduce the severity of myocarditis compared with the EAM without treatment rats by comparing the echocardiographic data, myocardial CD4 + , macrophages, neutrophil infiltrations, and the heart weight/body weight ratio in 3 weeks. The levels of inflammatory cytokines were not lower in the thalidomide and DPP4 inhibitor-treated group than in the untreated group in 3 weeks. In 6 weeks, thalidomide and DPP4 inhibitors did not reduce the fibrosis area compared to untreated groups., Conclusions: Although thalidomide and the DPP4 inhibitor had an immunomodulatory effect and are used against inflammatory diseases, they did not ameliorate myocardial inflammation and fibrosis in this rat model of EAM., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2023. The Korean Society of Cardiology.)

Aim: To examine the effect of oral diabetes medication on the risk of dementia in an elderly cohort with type 2 diabetes.Methods: This was a population-based cohort study using the Korean National Health Insurance claims data from 2002 to 2013. Elderly subjects (60 years of age or older) with and without type 2 diabetes were included; patients with new-onset type 2 diabetes were further divided into the oral diabetes medication group and no-medication group.Results: Among 278,290 patients with type 2 diabetes, 56,587 developed dementia (20.3%) over 11 years of follow-up. Type 2 diabetes was associated with a 1.69-fold increased risk of dementia (95% CI 1.66-1.72). Among patients with newly diagnosed type 2 diabetes, the risk of dementia was lower in the oral diabetes medication group than in the no-medication group (adjusted hazard ratio [aHR], 0.79; 95% CI 0.77-0.81). Lower risk of dementia was particularly noticeable in all of the combination therapy groups and especially lower in the combination therapy group treated with dipeptidyl peptidase 4 inhibitor (aHR 0.48, 95% CI 0.45-0.51).Conclusion: Overall, the use of oral diabetes medication in type 2 diabetes patients significantly decreased the risk of dementia. [ABSTRACT FROM AUTHOR]

Diabetes mellitus relates a metabolic disorder of collective aetiology which is characterized by chronic hyperglycaemia caused due to disturbances of carbohydrate, lipid and protein metabolism due to impaired β cell function of pancreas or insulin resistance or both. Dipeptidyl peptidase-4 (DPP-4) inhibitors have recently emerged as a new class of antidiabetic that show favorable results in improving glycemic control with a minimal risk of hypoglycemia and weight gain. Teneligliptin is a recently developed oral dipeptidyl peptidase 4 inhibitor indicated for the management of type 2 diabetes mellitus. Teneligliptin, characterized by a "J-shaped" structure formed by five consecutive rings which give unique binding characteristics, reflect in higher potency than other dipeptidyl peptidase 4 inhibitor. Teneligliptin is a novel antihyperglycemic agent with a preferable profile in terms of long-term efficacy and safety in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article offers a study on the effects of alogliptin on blood pressure and arterial stiffness in hypertensive patients with type 2 diabetes mellitus (T2DM). Topics discussed include Blood pressure and brachial-ankle pulse wave velocity (baPWV) were measured before and after 3, 6, and 12 months of treatment with alogliptin in 22 hypertensive patients with T2DM; and concludes that alogliptin was associated with improvements not only in glucose metabolism.

• Safety data are lacking on SGLT2i or DPP4i use prior to pregnancy. • Compared to sulfonylureas, preconception SGLT2i or DPP4i exposure was not associated with a difference in A1c, or risk of miscarriage or congenital anomaly. SGLT2i was associated with a slightly lower risk of miscarriage, induced abortion or stillbirth. • Neither SGLT2i nor DPP4i use at least 3 months before pregnancy is associated with a higher risk of adversity when compared to a sulfonylurea agent. SGLT2i may be associated with a lower risk of pregnancy loss. To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri -conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies. This population-based cohort study used administrative datasets for all of Ontario, Canada, and included women eligible for free medication coverage and who achieved a recognized pregnancy from April 2007-November 2021. Exposure was a SGLT2i, DPP4i or sulfonylurea (referent) dispensed at least 90 days preconception. Study outcomes included differences in periconceptional A1c; miscarriage, induced abortion, or stillbirth; and any congenital anomaly – the latter two outcomes assessed using propensity score overlap weighting. The mean (SD) periconceptional A1c was 8.1 % (2.0) among those prescribed any sulfonylurea, compared with 8.3 % (2.0) with a DPP4i and 7.8 % (1.6) with any SGLT2i. The risk of pregnancy loss was lowest among those exclusively prescribed a SGLT2i (relative risk [RR] 0.51, 95 % CI 0.22 to 0.91). Risk of a congenital anomaly at birth did not differ significantly comparing DPP4i or SGLT2i to sulfonylurea agents. Neither SGLT2i nor DPP4i use before pregnancy was associated with a difference in A1c, or a higher risk of selective adverse outcomes, compared to sulfonylureas. Future larger studies are required, including assessment of medication use after conception, during the critical period of embryogenesis. [ABSTRACT FROM AUTHOR]

Surendra Kumar Sharma,1 A Panneerselvam,2 KP Singh,3 Girish Parmar,4 Pradeep Gadge,5 Onkar C Swami6 1Diabetes, Thyroid and Endocrine Centre, Galaxy Speciality Centre, Jaipur, 2Aruna Diabetes Centre, Chennai, 3Fortis Hospital, Sector 62, Phase VIII, Mohali, 4Kokilaben Dhirubhai Ambani Hospital, Andheri (W), Mumbai, 5Dr Gadge’s Diabetes Care Centre, Mumbai, 6Unichem Laboratories Ltd, Jogeshwari (W), Mumbai, India Abstract: Teneligliptin is a recently developed oral dipeptidyl peptidase 4 inhibitor indicated for the management of type 2 diabetes mellitus (T2DM) in adults along with diet and exercise. Teneligliptin has been recently available in Japan (Teneria®), Argentina (Teneglucon®), and India (Tenepure; Teneza) at relatively affordable price. This is a positive step toward the management of T2DM in developing countries, where the cost of medicine is out-of-pocket expenditure and is a limiting factor for health care. This review evaluates the efficacy and safety of teneligliptin in the management of T2DM. Teneligliptin has been systematically evaluated in T2DM as monotherapy with diet and exercise and in combination with metformin, glimepiride, pioglitazone, and insulin in short-term (12 weeks) and long-term (52 weeks) studies. These studies have reported a reduction in HbA1c of 0.8%–0.9% within 12 weeks of therapy. Two 52-week studies reported sustained improvement in glycemic control with teneligliptin. Teneligliptin has been found to be well tolerated, and the safety profile is similar to other dipeptidyl peptidase 4 inhibitors. Hypoglycemia and constipation are the main adverse events. Teneligliptin can be administered safely to patients with mild, moderate, or severe renal impairment or end-stage renal disease without dose adjustment. Similarly, it can be used in patients with mild-to-moderate hepatic impairment. Teneligliptin is effective and well tolerated and may have an important role in the management of T2DM. Keywords: diabetes mellitus, dipeptidyl peptidase 4 inhibitor, newer DPP-4 inhibitor, teneligliptin, India

BackgroundWe compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.MethodsThe present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.ResultsThe mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002).ConclusionAs an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Aims/Introduction: Recent data showed that dipeptidyl peptidase 4 (DPP‐4) inhibitors exert a lipid‐lowering effect in diabetes patients. However, the mechanism of action is not yet clearly understood. We investigated the effect of anagliptin on cholesterol metabolism and transport in the small intestine using non‐diabetic hyperlipidemic animals, to clarify the mechanisms underlying the cholesterol‐lowering action. Materials and Methods: Male apolipoprotein E (ApoE)‐deficient mice were orally administered anagliptin in the normal chow. Serum cholesterol levels and lipoprotein profiles were measured, and cholesterol transport was assessed by measuring the radioactivity in the tissues after oral loading of 14C‐labeled cholesterol (14C‐Chol). In additional experiments, effects of exendin‐4 in mice and of anagliptin in DPP‐4‐deficient rats were assessed. Effects on target gene expressions in the intestine were analyzed by quantitative polymerase chain reaction in normal mice. Results: The serum total and non‐high‐density lipoprotein cholesterol concentrations decreased after anagliptin treatment in the ApoE‐deficient mice. The cholesterol‐lowering effect was predominantly observed in the chylomicron fraction. The plasma 14C‐Chol radioactivity was significantly decreased by 26% at 2 h after cholesterol loading, and the fecal 14C‐Chol excretion was significantly increased by 38% at 72 h. The aforementioned effects on cholesterol transport were abrogated in rats lacking DPP‐4 activity, and exendin‐4 had no effect on the 14C‐Chol transport in ApoE‐deficient mice. Furthermore, significant decreases of the intestinal cholesterol transport‐related microsomal triglyceride transfer protein, acyl‐coenzyme A:cholesterol acyltransferase 2, ApoA2 and ApoC2 messenger ribonucleic acid expressions were observed in the mice treated with repeated doses of anagliptin. Conclusions: These findings suggest that anagliptin might exert a cholesterol‐lowering action through DPP‐4‐dependent and glucagon‐like peptide 1‐independent suppression of intestinal cholesterol transport. Anagliptin delayed the lipid transport from intestine to systemic circulation. This effect is DPP‐4‐dependent but GLP‐1R independent manner. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9 mg/kg/day, n = 8) and pacing control group (n = 8). Three additional dogs without rapid pacing were assigned into non-pacing group, which was used as sham in this study. In the dogs with rapid pacing, the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated and blood was sampled every week. After the entire protocol, atrial tissue was sampled for histological examinations using HE, Azan, and dihydroethidium (DHE) staining to evaluate any tissue damage or oxidative stress. The pacing control group exhibited a gradual AERP shortening and CV decrease along the time course as previously reported. In the linagliptin group, the AERP shortening was not affected, but the CV decrease was suppressed in comparison to the control group (p < 0.05). The AF inducibility was increased in the control group and suppressed in the linagliptin group (p < 0.05). The control group exhibited tissue fibrosis, the degree of which was suppressed in the linagliptin group. DHE staining exhibited suppression of the reactive oxygen species expression in the linagliptin group in comparison to the pacing control group. Linagliptin, a DPP-4-inhibitor, suppressed the AF inducibility, CV decrease, and overexpression of oxidative stress in the canine AF model. Such suppressive effects of linagliptin on AF in the canine model may possibly be related to the anti-oxidative effect. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications. DPP-4 has the capability to inactivate not only incretins, but also a series of cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. Pre-clinical studies suggested that DPP-4 inhibitors may have potential cardiovascular protective effects in addition to their antidiabetic actions. In recent years, a number of clinical trials have been conducted to evaluate the effect of different DPP-4 inhibitors on the cardiovascular system. We herein review the available clinical studies in cardiovascular effects played by each DPP-4 inhibitor and discuss the prospective application of DPP-4 inhibitors on cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Anagliptin (ANA) improves dyslipidemia in addition to blood glucose levels. However, there are no comparative studies on the effects of ANA and other dipeptidyl peptidase‐4 inhibitors on serum lipid profile. We compared the effects of ANA on serum lipid profile with those of alogliptin (ALO) in type 2 diabetes mellitus outpatients. Materials and Methods: The study participants were 87 type 2 diabetes mellitus patients who had been treated with dipeptidyl peptidase‐4 inhibitors for ≥8 weeks and had a low‐density lipoprotein cholesterol (LDL‐C) level of ≥120 mg/dL. Participants were switched to either 200 mg/day ANA or 25 mg/day ALO for 24 weeks. Results: There was no significant difference in percentage change in LDL‐C level at 24 weeks between the ANA and ALO groups. Treatment with ANA for 12 weeks significantly decreased LDL‐C levels, one of the secondary end‐points. Treatment with ANA for 24 weeks significantly improved apolipoprotein B‐100 levels, and the percentage change in LDL‐C levels at 24 weeks correlated significantly with the percentage change in apolipoprotein B‐100 levels in the ANA group. Conclusions: The LDL‐C‐lowering effects of ANA and ALO at 24 weeks were almost similar in patients with type 2 diabetes mellitus. However, the results showed a tendency for a decrease in LDL‐C level at 24 weeks in the ANA group, and that such improvement was mediated, at least in part, through the suppression of apolipoprotein B‐100 synthesis. [ABSTRACT FROM AUTHOR]

The present study evaluated the effect of anagliptin on intimal hyperplasia following carotid artery injury in Sprague-Dawley rats. Sprague-Dawley rats weighing 280-300 g were injured using a 2F Fogarty balloon embolectomy catheter. The rats were divided into injury-(saline) and anagliptin-(10 mg/kg/day) treated groups. vascular injuries were induced in the left carotid artery, followed by evaluation of neointima formation at 28 days. The right and left carotid arteries were harvested and evaluated with histological evaluation, and the plasma activity of glucagon-like peptide 1 receptor (GLP-1), stromal cell-derived factor (SDF)-1α, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were detected by ELISA analysis. Treatment with anagliptin decreased balloon injury-induced neointima formation, compared with the injury group (P<0.01). Body weight and food consumption did not alter following treatment with anagliptin. Anagliptin caused an increase in the serum active GLP-1 concentration, compared with the injury group. In addition, serum SDF-1α was significantly decreased by treatment with anagliptin (P<0.001). Anagliptin altered the serum activity of IL-6, IL-1β and TNF-α (P<0.01). The results of the present study demonstrated that anagliptin appeared to attenuate neointimal formation by inhibiting inflammatory cytokines and chemokines following balloon injury, and that treatment with a dipeptidyl peptidase 4 inhibitor may be useful for future preclinical studies and potentially for the inhibition of thrombosis formation following percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Sodium 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. Medical 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. DPP-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. Thus, patients can expect better plasma glucose control by DPP-4is if patients are taking increased dietary sodium intake. • The effect of DPP-4 inhibitor on glycemic control was significantly negatively correlated with the dietary sodium intake. • Patients can expect better plasma glucose control by DPP-4 inhibitor if patients are taking increased dietary sodium intake. • The effect of DPP-4 inhibitor on glycemic control may be predicted by dietary sodium intake estimation. [ABSTRACT FROM AUTHOR]

Introduction: Teneligliptin is a recently developed Dipeptidyl Peptidase 4 (DPP4) inhibitor. Teneligliptin is suitable for glycaemic control in Type 2 Diabetes Mellitus (T2DM) patients with renal impairment including end stage renal disease. Aim: To assess the efficacy and safety of teneligliptin in Asian Indian T2DM patients with early Diabetic Kidney Disease (DKD). Materials and Methods: This was a single centre, retrospective analysis of patients with early DKD, who received teneligliptin 20 mg once daily for 24 weeks. Data related to glycaemic parameters, kidney function, lipid levels, retinopathy, neuropathy and safety variables available at 12 and 24 weeks were analysed. Descriptive statistical analysis was carried out. Statistical significance was assessed at a 5% level. Results: Total 37 patients (21 males; 16 females) were analysed. Compared to baseline, significant reduction in Fasting Plasma Glucose (FPG) (mg/dl) (143.89±28.26 vs 125.78±20.52, p=0.001); Postprandial Glucose (PPG) (mg/dl) (200.62±41.88 vs 165.76±26.02, p=0.001); Glycated Haemoglobin (HbA1c) (%) (8.65±0.58 vs 8.17±0.54, p=0.001) was noted at 12 weeks. This trend was further continued for 24 weeks with significant reduction in mean FPG, PPG and HbA1c to 113.73±16.82 mg/dl (p=0.008); 142.95±20.76 mg/dl (p=0.001); and 7.65±0.45% (p=0.001) respectively. Significant improvement in serum creatinine (mg/ dl) (2.45±0.27 vs. 2.26±0.23, p=0.001) and eGFR (CKD-EPI), (ml/ min/1.73 m2 ) (53.35±4.24 vs. 55.08±4.19, p=0.001) was noted at 12 weeks and continued for 24 weeks with reduction in serum creatinine of 0.37±0.18 mg/dl (p=0.001) and increase of eGFR of 4.60±1.59 ml/min/1.73 m2 (p=0.001). At baseline, proteinuria was noted in all patients while at 24 weeks, 40.5% (p=0.001) patients did not report proteinuria. Significant improvements in lipid parameters with no deterioration in retinopathy and subjective improvement in peripheral neuropathy was also noted. No adverse events were noted. Conclusion: Teneligliptin reported significant and sustained improvement in glycaemic control in Asian Indian Patients of T2DM with early DKD and was well tolerated. Additionally, Teneligliptin reported significant improvement in renal function.

BackgroundThe aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes.MethodsIn this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics.ResultsUltimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P