Dipeptidyl Peptidase-4 Inhibitor Group Research Articles

Sodium-glucose cotransporter-2 inhibitors and incidence of atrial fibrillation in older adults with type 2 diabetes: a retrospective cohort analysis

ObjectivesTo investigate the risk of atrial fibrillation (AF) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitor (DPP4i) use in older US adults and across diverse subgroups.MethodsWe conducted a retrospective cohort analysis using claims data from 15% random samples of Medicare fee-for-service beneficiaries. Patients were adults with type 2 diabetes (T2D), no preexisting AF, and were newly initiated on SGLT2i or DPP4i. The outcome was the first incident AF. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates between the treatment groups including sociodemographics, comorbidities, and co-medications. Cox regression models were used to assess the effect of SGLT2i compared to DPP4i on incident AF.ResultsOf the 97,436 eligible individuals (mean age 71.2 ± 9.8 years, 54.6% women), 1.01% (n = 983) had incident AF over a median follow-up of 361 days. The adjusted incidence rate was 8.39 (95% CI: 6.67–9.99) and 11.70 (95% CI: 10.9–12.55) per 1,000 person-years in the SGLT2i and DPP4i groups, respectively. SGLT2is were associated with a significantly lower risk of incident AF (HR 0.73; 95% CI, 0.57 to 0.91; p = 0.01) than DPP4is. The risk reduction of incident AF was significant in non-Hispanic White individuals and subgroups with existing atherosclerotic cardiovascular diseases and chronic kidney disease.ConclusionCompared to the use of DPP4i, that of SGLT2i was associated with a lower risk of AF in patients with T2D. Our findings contribute to the real-world evidence regarding the effectiveness of SGLT2i in preventing AF and support a tailored therapeutic approach to optimize treatment selection based on individual characteristics.

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.

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

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

Comparison of incident hypertension between SGLT2 inhibitors vs. DPP4 inhibitors.

Although several randomized clinical trials have reported the potential benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. We analyzed individuals with diabetes who were newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of hypertension. A propensity score matching algorithm was employed to compare the subsequent development of hypertension between the SGLT2i and DPP4i groups. After propensity score matching, 5708 well-balanced pairs of SGLT2i and DPP4i users were identified. SGLT2i administration was associated with a reduced risk of hypertension (HR 0.91, 95% CI: 0.84-0.97). The advantage of SGLT2i use over DPP4i use for incident hypertension was generally consistent in several sensitivity analyses, and subgroup analyses showed that SGLT2i use was significantly associated with a lower risk of hypertension in men, patients with baseline HbA1c of <7.5%, and baseline systolic blood pressure ≥127 mmHg. Our investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of hypertension in individuals with diabetes.

Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study

ObjectiveTo investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer.DesignScandinavian cohort study.SettingDenmark, Norway, and Sweden, 2007-21.ParticipantsPatients who started GLP1 receptor agonist...

Preventing CXCL12 elevation helps to reduce acute exacerbation of COPD in individuals co-existing type-2 diabetes: A bioinformatics and clinical pharmacology study

AimsTo investigate the immunology shared mechanisms underlying chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) and examine the impact of anti-diabetic drugs on acute exacerbation of COPD (AECOPD). MethodsWe analyzed GSE76925, GSE76894, GSE37768, and GSE25724 to identify differentially expressed genes. Hub-genes were identified through protein–protein interaction network analysis and evaluated by the receiver operating characteristic curve. CXCL12 emerged as a robust biomarker, and its correlation with lung function and CD8+ T cells were further quantified and validated. The activated signaling pathways were inferred through Gene set enrichment analysis (GSEA). The retrospective clinical analysis was executed to identify the influence of dipeptidyl peptidase-4 inhibitors (DPP-4i) on CXCL12 and evaluate the drug’s efficacy in AECOPD. ResultsThe significant up-regulation of CXCL12 expression in patients with two diseases were revealed. CXCL12 exhibited a negative correlation with pulmonary function (r = -0.551, p < 0.05). Consistent with analysis in GSE76925 and GSE76894, the positive correlation between the proportion of CD8+ T cells was demonstrated(r=0.469, p<0.05). GSEA identified “cytokines interaction” as an activated signaling pathway, and the clinical study revealed the correlation between CXCL12 and IL-6 (r=0.668, p<0.05). In patients with COPD and T2DM, DDP-4i treatment exhibited significantly higher serum CXCL12, compared to GLP-1RA. Analysis of 187 COPD patients with T2DM indicated that the DPP-4i group had a higher frequency of AECOPD compared to the GLP-1RA group (OR 1.287, 95%CI [1.018–2.136]). ConclusionsCXCL12 may represent a therapeutic target for COPD and T2DM. GLP-1RA treatment may be associated with lower CXCL12 levels and a lower risk of AECOPD compared to DPP-4i treatment.Clinical Trial Registration: China Clinical Trial Registration Center（ChiCTR2200055611）.

Novel Antidiabetic Drugs and the Risk of Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The aim of this study is to compare the effect of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes (DM2). Methods: We systematically searched the databases Pubmed, Embase, and Clinicaltrials up to October 2, 2023, for randomized clinical trials (RCTs) of drugs from the GLP-1RA, SGLT-2i, and DPP-4i groups, with at least 24 weeks duration, including adult patients with DM2 and reported ocular complications. A pairwise meta-analysis was performed to calculate the odds ratio (OR) of DR incidents. Results: Our study included 61 RCTs with a total of 188,463 patients and 2773 DR events. Pairwise meta-analysis showed that included drug groups did not differ in the risk of DR events: GLP1-RA vs. placebo (OR 1.08; CI 95% 0.94, 1.23), DPP-4i vs. placebo (OR 1.10; CI 95% 0.84, 1.42), SGLT2i vs. placebo (OR 1.02; CI 95% 0.76, 1.37). Empagliflozin may be associated with a lower risk of DR, but this sub-analysis included only three RCTs (OR 0.38; 95% CI 0.17, 0.88, p = 0.02). Conclusions: Based on currently available knowledge, it is challenging to conclude that the new antidiabetic drugs significantly differ in their effect on DR complications.

Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study.

No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70-0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60-0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79-0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72-0.89, all p <0.05) across various sensitivity analyses. Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.

Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.

Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.

Dipeptidyl peptidase-4 inhibitors versus sulfonylureas on the top of metformin in patients with diabetes and acute myocardial infarction.

Recent trials have shown that both the extent of glycated hemoglobin reduction and the duration of enhanced glycemic control are major factors that may affect cardiovascular outcome results. We aimed to investigate the impact of metformin (MET) combined with dipeptidyl peptidase-4 (DPP4) inhibitors or sulfonylureas (SU) on long-term clinical outcomes in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM). This study was a prospective cohort trial. From November 2011 to December 2015, a total of 13,104 AMI patients were consecutively enrolled from the Korea AMI registry-National Institutes of Health. The patients were divided into the MET + DPP4 inhibitors group and the MET + SU group. The primary endpoint, major adverse cardiac events (MACE), was defined as the composite of all-cause death, recurrent myocardial infarction (MI), and any repeat revascularization up to 3-year follow-up. To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed. Baseline well-matched two groups were generated (the MET + DPP4 inhibitors group, n=468 and the MET + SU group, n=468). During 3-year clinical follow-up, the cumulative incidence of MACE between the two groups was not significantly different after adjustment (16.8% for MET + DPP4 inhibitors group vs. 19.4% for MET + SU group, P=0.302). However, the MET + DPP4 inhibitors group was associated with reduced risk of MI [1.3% vs. 4.9%; hazard ratio (HR): 0.228, 95% confidence interval (CI): 0.090-0.580, P=0.001] than the MET + SU group. In patients with AMI and type 2 DM, the use of MET combined with DPP4 inhibitors was associated with reduced incidence of recurrent MI than MET combined with SU during 3-year follow-up.

Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

Effects of SGLT2 Inhibitors and DPP-4 Inhibitors on Advanced Glycation End Products.

Clinical trials have revealed that sodium glucose cotransporter 2 (SGLT2) inhibitors suppress the onset of heart failure and cardiovascular death in diabetic patients. On the other hand, few reports have been published concerning such effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. We undertook the present study to evaluate the effects of SGLT2 inhibitors and DPP-4 inhibitors on the advanced glycation end products (AGEs), well known as a risk factor for the development of cardiovascular disorders.Type 2 diabetes mellitus were divided into two groups and treated with either SGLT2 inhibitors or DPP-4 inhibitors for 3 months. Before and after the 3-month treatment period with each drug, the AGEs and diabetes-related parameters were measured. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured as one of the AGEs.In the SGLT2 inhibitor group, both the blood HbA1c and MG-H1 levels decreased significantly after the 3-month treatment period. In the DPP-4 inhibitor group, only the blood HbA1c level decreased significantly, with no significant change of the blood MG-H1 level.SGLT2 inhibitor reduced both the blood levels of HbA1c and AGEs (MG-H1). Considering that the blood levels of AGEs are associated with the risk of heart failure and cardiovascular disorders, the results of the present study suggest that the effect of SGLT2 inhibitors in suppressing cardiovascular death might be mediated by the reduction in the blood levels of AGEs induced by this class of drugs. DPP-4 inhibitors showed no significant effects on the blood levels of AGEs.

Comparative effectiveness of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real-world data analysis.

To compare the effects of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan. This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis-4 (FIB-4) index, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t-test in the full population and in subgroups stratified by baseline characteristics. Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB-4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB-4 index and HbA1c. In this study, improvements in various measures, including ALT, the FIB-4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan.

Abstract 16543: New-Onset Infective Endocarditis in Diabetic Patients Receiving SGLT2I and DPP4I: A Population-Based Cohort Study

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2I) have been suggested to have beneficial effects against infection. However, the comparative risks of new onset infective endocarditis between SGLT2Is and dipeptidyl peptidase-4 inhibitors (DPP4Is) remain unknown. Objective: This real-world study aims to compare the risks of infective endocarditis upon exposure to SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I). Methods: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 using a territory-wide registry in Hong Kong. The primary outcome was new-onset infective endocarditis. The secondary outcome was cardiovascular-related mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was applied to identify significant associations. Results: This cohort included 75638 T2DM patients (median age: 62.3 years old [SD: 12.8]; 55.79 % males). The SGLT2I and DPP4I groups consisted of 28774 patients and 46864 patients, respectively. After matching, 104 and 161 endocarditis events in the SGLT2I and DPP4I groups occurred over a follow-up of 5.6 years. SGLT2I use was associated with lower risks of infective endocarditis (Hazard ratio [HR]: 0.58; 95% Confidence Interval [CI]: 0.41-0.81; p=0.0016) and cardiovascular mortality (HR: 0.49; 95% CI: 0.33-0.72; p=0.0002) compared to DPP4I use after adjustments for demographics, comorbidities, medications, renal function and HbA1c levels. Similar associations were observed in subgroup analyses by gender, hypertension, arrhythmia, or renal disease, competing risk and sensitivity analyses. Conclusions: SGLT2I use is associated with lower risks of new-onset infective endocarditis compared to DPP4I.

THU287 Comparison Of Renal Protective Effects Between SGLT2 Inhibitors And DPP4 Inhibitors In Real-World Clinical Practice

Abstract Disclosure: H. Park: None. S. Park: None. S. Kwon: None. H. Kim: None. D. Byun: None. Recent prospective randomized studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors had renal protective effects compared to placebo. In this study, we compared the renal composite outcomes between patients with diabetes treated with SGLT2 inhibitors and those treated with dipeptidyl peptidase 4 (DPP4) inhibitors using real-world clinical data. This retrospective observational study used the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database at four different university hospitals (Soonchunhyang university hospitals in Seoul, Bucheon, Chunan, and Gumi) in Korea. Subjects prescribed SGLT2 inhibitors or DPP4 inhibitors for at least 90 days were included in the SGLT2 inhibitor or DPP4 inhibitor group, respectively. Subjects prescribed GLP-1 receptor agonist or insulin were excluded in both groups. Renal composite outcomes included a 30% decline in estimated glomerular filtration rate (eGFR) compared to baseline or creatinine doubling or dialysis or death from any cause. After propensity score matching, clinical characteristics in each group at each hospital were well balanced at baseline. Our results from hospitals in Seoul, Bucheon, and Gumi have shown that SGLT2 inhibitor decreased renal composite outcomes compared to DPP4 inhibitor (hazard ratio (HR) 0.644, p=0.020; HR 0.560, p&amp;lt;0.001; HR 0.657, p=0.010, respectively). Furthermore, when all the data were combined, renal composite outcomes were significantly lower in the SGLT2 inhibitor group compared to the DPP4 inhibitor group (HR 0.659, p&amp;lt;0.001). In conclusion, SGLT2 inhibitors effectively reduce renal composite outcomes compared to DPP4 inhibitors in real-world clinical practice. Presentation: Thursday, June 15, 2023

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

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

Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus

BackgroundAlthough sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus, real-world evidence regarding their benefits to diabetic patients with acute myocardial infarction (AMI) is insufficient. This study evaluated cardiovascular outcomes by comparing SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with metformin in diabetic patients with AMI.MethodsThis study involved 779 diabetic participants with AMI from a Korean nationwide multicenter observational cohort, who were divided into two groups: (1) metformin plus SGLT2i group (SGLT2i group, n = 186) and (2) metformin plus DPP-4i (DPP-4i group, n = 593). The primary endpoint was one year of major adverse composite events (MACEs), a composite outcome of all-cause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. To balance the baseline differences, inverse probability of treatment weighting (IPTW) was performed.ResultsAfter IPTW, the rate of MACEs in the SGLT2i group was not significantly lower than that in the DPP-4i group (hazard ratio [HR], 0.99; 95% confidence interval [Cl], 0.46 to 2.14, p = 0.983). In the unadjusted and adjusted analyses, all items for clinical outcomes were comparable between the two groups. In our exploratory analysis, the left ventricular ejection fraction showed a significant improvement in the SGLT2i group than in the DPP-4i group before achieving statistical balancing (6.10 ± 8.30 versus 2.95 ± 10.34, p = 0.007) and after IPTW adjustment (6.91 ± 8.91 versus 3.13 ± 10.41, p = 0.027).ConclusionsOur findings demonstrated that SGLT2i did not influence the rate of MACEs compared with DPP-4i in combination with metformin in diabetic patients with AMI but did improve left ventricular ejection fraction.Trial registrationNot applicable (retrospectively registered).

Overall Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Versus Dipeptidyl-Peptidase 4 Inhibitors: Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT study).

Evidence of a direct comparison between dipeptidyl-peptidase 4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) remains lacking, and no clear treatment strategy or rationale has been established using these drugs. This study aimed to compare the overall efficacy and safety of DPP-4is and the SGLT2i luseogliflozin in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had not used antidiabetic agents or who had used antidiabetic agents other than SGLT2is and DPP-4is were enrolled in the study after written informed consent had been obtained. The enrolled patients were subsequently randomly assigned to either the luseogliflozin or DPP-4i group and followed up for 52weeks. The primary (composite) endpoint was the proportion of patients who showed improvement in ≥ 3 endpoints among the following five endpoints from baseline to week 52: glycated hemoglobin (HbA1c), weight, estimated glomerular filtration rate (eGFR), systolic blood pressure, and pulse rate. A total of 623 patients were enrolled in the study and subsequently randomized to either the luseogliflozin or DPP-4i groups. The proportion of patients who showed improvement in ≥ 3 endpoints at week 52 was significantly higher in the luseogliflozin group (58.9%) than in the DPP-4i group (35.0%) (p < 0.001). When stratified by body mass index (BMI) (< 25 or ≥ 25kg/m2) or age (< 65 or ≥ 65years), regardless of BMI or age, the proportion of patients who achieved the composite endpoint was significantly higher in the luseogliflozin group than in the DPP-4i group. Hepatic function and high-density lipoprotein-cholesterol were also significantly improved in the luseogliflozin group compared with the DPP-4i group. The frequency of non-serious/serious adverse events did not differ between the groups. This study showed the overall efficacy of luseogliflozin compared with DPP-4is over the mid/long term, regardless of BMI or age. The results suggest the importance of assessing multiple aspects regarding the effects of diabetes management. jRCTs031180241.

881-P: Heterogenous Effects of SGLT2 Inhibitors on Nephrolithiasis in Older Adults with Type 2 Diabetes

Mechanistic studies suggested that sodium-glucose cotransporter-2 inhibitors (SGLT2i) may reduce the risk of nephrolithiasis. We aimed to further assess this association using a real-world population of type 2 diabetes (T2D) patients. Among a 15% random sample of 2017-2018 Medicare fee-for-service beneficiaries with T2D, we identified new initiators of SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i). We followed the cohort until the first medical encounter with diagnosis of nephrolithiasis, death, or 12/31/2018. Inverse probability treatment weighting was used to balance the baseline covariates including sociodemographics, prior comorbidities and medications. Of 116,506 included individuals (age 72±10 years, 53% women), 0.96% developed nephrolithiasis over a median follow-up of 360 days. The crude incidence rate was 9.89 (95% confidence interval [CI] 8.49-11.52) and 11.02 (95% CI 10.34-11.73) per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i exposure was associated with a significantly lower risk of nephrolithiasis (hazard ratio 0.81 [95% CI 0.66-0.99]). This effect was more evident in men, non-Hispanic Black (NHB) individuals, and those without a history of nephrolithiasis. (Figure) SGLT2i was associated with a lower risk of nephrolithiasis, and the effect was more pronounced in men, NHB, and those without a history of nephrolithiasis. Disclosure Y.Li: None. H.Shao: Consultant; Lilly Diabetes. Y.Guo: None. Y.Zhang: None. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. L.Shi: None. J.Bian: None. A.G.Winterstein: Consultant; Bayer Inc., Genentech, Inc., Ipsen Biopharmaceuticals, Inc., Research Support; Merck Sharp &amp; Dohme Corp. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.

880-P: Effects of Sodium–Glucose Cotransporter-2 Inhibitors on the Risk of Atrial Fibrillation in Older Adults with Type 2 Diabetes

Clinical evidence suggested a protective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the risk of atrial fibrillation (AF) in type 2 diabetes (T2D) patients, but the results were mixed. We aimed to compare the risk of AF in SGLT2i users compared to dipeptidyl peptidase-4 inhibitors (DPP4i) users and determine the effect in different subgroups. Using a 15% random sample of 2017-2018 Medicare claims data, we identified individuals with T2D, no preexisting AF, and initiated SGLT2i or DPP4i. The index date was defined as the date of the first filled prescription of SGLT2i or DPP4i. The outcome was the first incident of diagnosed AF. Inverse probability treatment weighted Cox regression models were used for analyses. Of the 97,660 eligible individuals (age 71.2±9.8 years, 54.6% women), 1.01% (n=989) had incident AF over a median follow-up of 361 days. The crude incidence rate was 8.39 (95% CI: 6.67-9.99) and 11.70 (95% CI: 10.9-12.55) per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i was associated with a significantly lower risk of incident AF (HR 0.72 [95% CI 0.56-0.89]) than DPP4i. The risk reduction of incident AF was more pronounced in Hispanic individuals and subgroups with existing cardiovascular (CV) and renal conditions. (Figure) Use of SGLT2i was associated with a lower risk of AF in individuals with T2D. Disclosure Y.Li: None. Y.Guo: None. S.Kimmel: Consultant; GlaxoSmithKline plc., Other Relationship; Janssen Research &amp; Development, LLC. J.Bian: None. D.Schatz: Advisory Panel; Medtronic, Avotres Inc., QuLab Medical Ltd., Kriya Therapeutics. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.