Dipeptidyl Peptidase-4 Inhibitor Group Research Articles

SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to have many benefits for patients with type 2 diabetes. However, whether SGLT2 inhibitors increase the risk of acute kidney injury (AKI) remains unknown. We examined the association of AKI hospitalization with prior initiation of an SGLT2 inhibitor compared with initiation of a dipeptidyl peptidase 4 (DPP-4) inhibitor or a glucagon-like peptide 1 receptor agonist (GLP-1RA) among older adults with type 2 diabetes in routine practice. Population-based cohort study. Older adults aged at least 66 years with type 2 diabetes enrolled in Medicare fee-for-service and who were new users of SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1RA agents in the interval from March 2013 to December2017. New use of an SGLT2 inhibitor versus new use of a DPP-4 inhibitor or GLP-1RA. The primary outcome was hospitalization for AKI, defined as a discharge diagnosis of AKI in the primary or secondary position. New users of SGLT2 inhibitors were matched at a 1:1 ratio to new users of DPP-4 inhibitors or GLP-1RAs using propensity scores in 2 pairwise comparisons. Cox proportional hazards regression models generated hazard ratios (HRs) with 95% CIs in propensity score-matched groups. Totals of 68,130 and 71,477 new users of SGLT2 inhibitors were matched to new users of DPP-4 inhibitors or GLP-1RAs, respectively. Overall, the mean age of study participants was 72 years. The risk of AKI was lower in the SGLT2 inhibitor group than in the DPP-4 inhibitor group (HR, 0.71 [95% CI, 0.65-0.76]) or the GLP-1RA group (HR, 0.81 [95% CI, 0.75-0.87]). Residual confounding and lack of laboratory data. Among older adults with type 2 diabetes, initiation of an SGLT2 inhibitor was associated with a reduced risk of AKI compared with initiation of a DPP-4 inhibitor or a GLP-1RA.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM.

Risk of Cardiovascular Events and Medical Cost of Dapagliflozin and Dipeptidyl Peptidase-4 Inhibitors

This study compared dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, and dipeptidyl peptidase-4 inhibitors (DPP-4i) with regard to cardiovascular (CV) event incidence and direct medical costs during type 2 diabetes treatment. A retrospective cohort study was conducted using national health insurance claims data from September 1, 2014, to June 30, 2018, of patients in Korea. Patients who were prescribed dapagliflozin and DPP-4i for the first time were included. The primary outcome was the incidence of a composite of major adverse CV events (MACEs)—nonfatal myocardial infarction, nonfatal stroke, or in-hospital CV death. Proportional hazard models after propensity score weighting were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE in the dapagliflozin and DPP-4i groups. A decision analytic model was used to compare direct medical costs between the two treatment groups from a healthcare provider’s perspective. Of the 260,336 patients in the cohort, 23,147 and 237,189 received dapagliflozin and DPP-4i, respectively. During the follow-up, 184 patients receiving dapagliflozin and 3,674 receiving DPP-4i (incidence, 6.47 and 11.33 events/1,000 person-years, respectively) had MACE. The adjusted HR of MACE for dapagliflozin compared with that for DPP-4i was 0.69 (95% CI 0.57–0.83). The corresponding HRs were consistent among patients with and without underlying CV disease. The estimated direct medical cost appeared to be lower by $68,452 in the dapagliflozin group than that in the DPP-4i group for 3 years, in 1,000 hypothetical patients. In this population-based cohort study, the use of dapagliflozin instead of DPP-4i was associated with a reduced risk of MACE, which subsequently reduced direct medical costs. These data provide valuable information to patients, practitioners, and authorities regarding the risk of CV events associated with dapagliflozin versus DPP-4i use in clinical practice.

Lowering of blood pressure and pulse rate by switching from DPP-4 inhibitor to luseogliflozin in patients with type 2 diabetes complicated with hypertension: A multicenter, prospective, randomized, open-label, parallel-group comparison trial (LUNA study)

AimsSodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces clinic blood pressure (BP), but the effects on BP circadian rhythm remain unclear. The present study aimed to determine the nighttime antihypertensive effect of SGLT2i compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) in patients with type 2 diabetes and hypertension. Materials and MethodsIn this randomized, open-label, parallel-group trial, patients treated with DPP-4i were either switched to luseogliflozin 2.5 mg/day (Luseo group;n = 30) or continued DPP-4i (DPP-4i group;n = 26). The patients undertook 24-h ambulatory BP monitoring before and 8 weeks after the group allocation. The primary endpoint was mean change in nighttime systolic BP (SBP). ResultsNighttime SBP, as well as daytime SBP, was significantly reduced in the Luseo group compared with the DPP-4i group (nighttime, −4.0 ± 11.4 vs. 3.6 ± 10.7 mmHg,P = 0.01; daytime, −4.4 ± 10.9 vs. 3.7 ± 11.9 mmHg,P = 0.01). Similarly, nighttimepulse rate(PR) was significantly reduced in the Luseo group (−2.0 ± 4.8 vs. 0.9 ± 4.8 bpm,P = 0.03). The proportion of patients with abnormal BP circadian rhythms (non-dipper pattern plus riser pattern) was significantly lower in the Luseo group (36.6% vs. 56.7%,P < 0.05). ConclusionsSwitching from DPP-4i to luseogliflozin decreased nighttime SBP and PR; moreover, BP circadian rhythm was improved.

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study

IntroductionTo investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM).MethodsA multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility (n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population.ResultsA total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is (n = 4550) or other glucose-lowering drugs (n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35–0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39–1.08; p = 0.099).ConclusionsThe results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19.

Repurposing DPP-4 Inhibitors for Colorectal Cancer: A Retrospective and Single Center Study.

Simple SummaryColorectal cancer is one of the most common causes and the leading cause of cancer deaths worldwide. Its poor prognosis highlights the urgent need for more effective treatments. Repurposing approved drugs is a promising strategy as preclinical screenings can be minimized. The aim of our retrospective study was to investigate the potential of Dipeptidyl-peptidase 4 (DPP4)-inhibitors, which are safe Food and Drug Association (FDA)-approved drugs for treating diabetes, in treating CRC patients. Our findings conclude that CRC patients with diabetes and treated with DPP4-inhibitors in our hospital during 2006–2015, their 5-year prognosis following curative resection was significantly better than those treated with metformin. We further showed that their prognosis was associated with immune cell population features that associated with better prognosis, and immune cell profile is a biomarker for predicting the prognosis of DPP4-inhibitors treated CRC patients.Background: There have been studies reporting the crucial roles of Dipeptidyl-peptidase 4 (DPP4) in colorectal cancer (CRC) initiation and progression, whereas DPP4-inhibitors are safe Food and Drug Association (FDA)-approved drugs for treating diabetes. This study aims to investigate the association between DPP4-inhibitor treatment and the prognosis of CRC patients. Methods: Clinical data of CRC patients with diabetes and the prescription of DPP4-inhibitors who had undergone curative surgery in our hospital between January 2006 and December 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared to those treated with metformin. Results: The DPP4-inhibitor patient group showed a significantly better 5-year disease-free survival (median DFS = 1733 days, 95% CI = 1596 to 1870 days) when compared to the metformin group (p = 0.030, median DFS = 1382 days, 95% CI = 1246 to 1518 days). 33 out of the 92 patients in the metformin group showed recurrence whereas only 3 of the 26 patients in the DPP4-inhibitor group showed recurrence (p = 0.033). Cox regression analysis demonstrated that DPP4-inhibitor application is a favorable factor associated with a lower risk of recurrence (Hazard ratio = 0.200, p = 0.035). Furthermore, our results suggested that the immune cell profile of CRC patients is a potential biomarker for response to DPP4-inhibitor treatment. Conclusion: This study demonstrated the association of DPP4-inhibitor treatment with a better prognosis of CRC patients.

Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea.

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group).MethodsThis was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction.ResultsTwenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.013; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index.ConclusionThere was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.

Comparative Effects of Metformin and Dipeptidyl Peptidase-4 Inhibitors in Japanese Obese Patients with Type 2 Diabetes: A Claims Database Study.

IntroductionMetformin has demonstrated favorable effects on glycemic control in patients with type 2 diabetes (T2D), regardless of the body mass index (BMI). On the contrary, dipeptidyl peptidase-4 inhibitors (DPP-4is) are reportedly less effective in patients having high BMI values (≥ 25 or ≥ 30). The aim of this study was to compare metformin and DPP-4is as first-line treatment for their effects on glycemic control and improvement of other health outcomes among obese and non-obese Japanese patients with T2D.MethodsA Japanese health insurance claims database that also included annual medical checkup data was used. This database included data on company employees who were members of health insurance societies and their family members. Most patients were aged < 65 years and most were men. Inclusion criteria were: (1) a first T2D diagnosis between May 2010 and June 2017; (2) either metformin or a DPP-4i prescribed as the first-line antidiabetic therapy; and (3) glycated hemoglobin (HbA1c) and BMI data available for the 3-month period immediately preceding the initiation of antidiabetic treatment (baseline). The reduction rate in excessive HbA1c (> 6.5%; primary outcome) and changes in fasting plasma glucose, BMI, triglyceride, cholesterol, and abdominal circumference (secondary outcomes) at 12 months from baseline were compared between treatments.ResultsWhen evaluated relative to the baseline BMI, the mean reduction rate in excessive HbA1c tended to be higher in the metformin group than in the DPP-4i group, especially in patients with BMI ≥ 25. Similarly, significant improvement was observed in most outcomes in obese patients prescribed metformin compared to those prescribed a DPP-4i. In contrast, in patients with BMI < 25, HbA1c reduction was greater in patients prescribed DPP-4i and fewer outcomes showed significant improvement in patients prescribed metformin.ConclusionIn obese Japanese patients with T2D, greater improvements in glycemic control and other outcomes were seen with metformin as first-line treatment for T2D compared with DPP-4is, although some limitations regarding the database information should be considered.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01101-2.

Effects of DPP4 Inhibitors on Renal Outcomes in Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Objectives:This meta-analysis of randomized clinical trials (RCT) intends to evaluate the efficacy of DPP4 Inhibitors (DPP4I) compared with placebo, other antidiabetics (or DPP4I) on renal outcomes, adverse events (AEs), and all-cause mortality.Methods:We searched relevant scientific database for RCTs with DPP4I and prespecified renal end point. The effect size (mean difference or risk ratio) was reported with its 95% confidence interval.Results:Eight RCTs (n = 39040 participants) were included in the analysis. The rate of change in eGFR was not different in DPP4 inhibitor and control group. DPP4I use beyond 52 weeks did not worsen albuminuria progression (RR 0.88; 95% CI 0.80 to 0.96; high quality evidence) compared to placebo. The risk of AEs within 52 weeks (RR 0.93; 95% CI 0.80 to 1.08; moderate quality evidence), beyond 52 weeks (RR 0.98; 95% CI 0.97 to 1.00; low quality evidence), and all-cause mortality (RR 1.04; 95% CI 0.96 to 1.12; very low quality evidence) were similar to placebo. In head-to-head comparison between two DPP4I studies, no significant differences were found between alogliptin and vildagliptin for improvement in eGFR, UACR, or AE at 24 weeks.Conclusions:DPP4I do not seem to provide persuasive benefit in the renal outcomes or all-cause mortality in diabetes mellitus, though there was no evidence for increased AEs.

Major adverse cardiovascular and limb events in patients with diabetes treated with GLP-1 receptor agonists vs DPP-4 inhibitors.

The safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) in major cardiovascular adverse events were previously examined in cardiovascular outcome trials. However, the effects of these drugs on adverse limb outcomes were poorly examined. This study aimed to determine the real-world outcomes of patients with diabetes mellitus receiving GLP1RAs as compared with those receiving DPP4is in terms of major adverse cardiovascular and limb events. A retrospective cohort study was conducted with data collected by the Taiwan National Health Insurance database between 1 May 2011 and 31 December 2017. Patients who were treated for type 2 diabetes with a GLP1RA or DDP4i during this period (n = 1,080,993), were identified. The primary outcome was a composite of major adverse limb events, defined as peripheral artery disease (PAD), critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for PAD, and amputation. The secondary cardiovascular outcome was the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Propensity-score matching (PSM) at a 1:3 ratio between GLP1RA and DPP4i groups was done to minimise possible selection bias. A total of 948,342 individuals treated between 1 May 2011 and 31 December 2017, were identified, with 4460 in the GLP1RA group and 13,380 in the DPP4i group after PSM. The incidence of primary composite outcome events was significantly lower in those treated with GLP1RAs compared with those treated with DPP4is (2.59 vs 4.22 events per 1000 person-years; subdistribution HR [SHR] 0.63 [95% CI 0.41, 0.96]), primarily due to lower rates of amputation (1.29 events per 1000 person-years for GLP1RAs vs 2.4 events per 1000 person-years for DPP4is; SHR 0.55 [95% CI 0.30, 0.99]). Treatment with GLP1RAs was also associated with significantly lower risks of secondary composite outcome events (11.02 vs 17.95 events per 1000 person-years; HR 0.62 [95% CI 0.51, 0.76]). Moreover, the observed beneficial effects of GLP1RAs on reducing composite adverse limb outcomes were particularly noticeable in the non-cardiovascular patients and statin users (p for interaction <0.05). In individuals with diabetes, the use of GLP1RAs was associated with significantly lower risks of major adverse limb events when compared with the use of DPP4is. The reduction in risk was driven largely by reduced rate of amputations. Moreover, treatment with GLP1RAs was also associated with lower risks of cardiovascular death, non-fatal stroke, non-fatal myocardial infarction and death from any cause. However, some unexplored confounding factors may exist in this observation study and future large-scale randomised controlled trials are needed.

Association between Add-On Dipeptidyl Peptidase-4 Inhibitor Therapy and Diabetic Retinopathy Progression

This study aimed to investigate the association of add-on dipeptidyl peptidase-4 inhibitor (DPP4i) therapy and the progression of diabetic retinopathy (DR). In this retrospective population-based cohort study, we examined Taiwanese patients with type 2 diabetes, preexisting DR, and aged ≥40 years from 2009 to 2013. Prescription of DPP4i was defined as a medication possession ratio of ≥80% during the first 6 months. The outcomes included vitreous hemorrhage (VH), tractional retinal detachment, macular edema, and interventions including retinal laser therapy, intravitreal injection (IVI), and vitrectomy. Of 1,767,640 patients, 62,824 were eligible for analysis. After matching, the DPP4i and non-DPP4i groups each contained 20,444 patients. The risks of VH (p = 0.013) and macular edema (p = 0.035) were higher in the DPP4i group. The DPP4i group also had higher risks of receiving surgical interventions (retinal laser therapy (p < 0.001), IVI (p = 0.049), vitrectomy (p < 0.001), and any surgical intervention (p < 0.001)). More patients in the DPP4i group received retinal laser therapy (p < 0.001) and IVI (p = 0.001) than in the non-DPP4i group. No between-group differences in cardiovascular outcomes were noted. In the real-world database study, add-on DPP4i therapy may be associated with the progression of DR in patients with type 2 diabetes. No additional cardiovascular risks were found. The early progression of DR in rapid glycemic control was inconclusive in our study. The possible effect of add-on DPP4i therapy in the progression of DR in patients with type 2 diabetes requires further research.

7-LB: Lowering of Blood Pressure and Pulse Rate by Switching from DPP-4 Inhibitor to Luseogliflozin in Patients with Type 2 Diabetes and Hypertension: A Multicenter, Prospective, Randomized, Open-Label, Parallel-Group Comparison Trial

Objective: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment had the effect of reducing blood pressure (BP) and cardiovascular events in recent mega-scale trials, but the effects on BP circadian rhythm remained unclear. The present study aimed to determine the nocturnal antihypertensive effect of SGLT2i compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) in patients with type 2 diabetes and hypertension. Research Design and Methods: In this randomized, open-label, parallel-group trial, patients treated with DPP-4i were either switched to luseogliflozin 2.5 mg/day (Luseo group; n=30) or continued DPP-4i (DPP-4i group; n=26). The patients undertook 24-h ambulatory BP monitoring before and 8 weeks after the group allocation. The primary endpoint was mean change in nighttime systolic BP (SBP). Results: Changes in both nighttime and daytime SBP were significantly reduced in the Luseo group compared with the DPP-4i group (nighttime, −4.0±11.4 vs. 3.6±10.7 mmHg, P=0.01; daytime, −4.4±10.9 vs. 3.7±11.9 mmHg, P=0.01). Similarly, nighttime pulse rate (PR) was significantly reduced in the Luseo group compared with the DPP-4i group (−2.0±4.8 vs. 0.9±4.8 bpm, P=0.03). Abnormal BP circadian rhythms (non-dipper and riser types) were significantly decreased in the Luseo group (56.7% to 36.6%, P&amp;lt;0.05). Conclusions: Switching from DPP-4i to luseogliflozin decreased not only daytime but also nighttime SBP and PR, and improved BP circadian rhythm. These improvements could be some of the factors involved in the cardiovascular event suppression observed with SGLT2i therapy. Disclosure R. Hashimoto-kameda: None. K. Cho: None. H. Nomoto: None. A. Nakamura: Research Support; Self; Boehringer Ingelheim International GmbH, Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Taisho Pharmaceutical Co., Ltd. K. Omori: None. S. Kawata: None. H. Kameda: None. T. Atsumi: Research Support; Self; Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K. K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., UCB Japan Co. Ltd., Speaker’s Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Co., UCB Japan Co. Ltd. H. Miyoshi: Research Support; Self; Abbott Japan Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Speaker’s Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K. K., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd. Funding Taisho Pharmaceutical Co., Ltd.

Comparative risk of musculoskeletal adverse reactions among new users of dipeptidyl peptidase-4 inhibitors: A retrospective cohort study

BackgroundThe effects of dipeptidyl peptidase-4 inhibitors (DPP4Is) on joint pain have been controversial. ObjectiveTo assess the comparative musculoskeletal (MSk) risk of DPP4Is vs. non-DPP4Is. MethodsThis study used a national claims database from January 2007 to December 2014. Exposure included the initiation of DPP4Is against the initiation of non-DPP4Is: metformin, sulfonylureas, thiazolidinediones, meglitinides, and glucagonlike peptide-1 receptor agonists (GLP-1 RAs). Insulin was not included in this study. Outcomes were newly diagnosed MSk conditions (arthralgia, arthropathy, and rheumatoid arthritis or other inflammatory polyarthropathies). Individuals exposed to DPP4Is were matched to those exposed to non-DPP4Is using a propensity score (PS). Balance between the DPP4I's group and the non-DPP4I's group was assessed using standardized differences for both continuous and categorical variables. Cox regressions were used to estimate hazard ratios (HRs) for MSk conditions. ResultsAmong PS-matched cohorts, incidence rates (IRs) for MSk conditions did not differ between DPP4I initiators and non-DPP4I initiators (HR = 1.01, 95% CI: 0.97–1.05). After stratifying non-DPP4Is by drug class, the results still showed that DPP4I initiators had similar MSk risk when compared to initiators of metformin, sulfonylureas, meglitinides, and GLP-1 RAs. However, thiazolidinedione initiators had higher risk of MSk conditions than DPP4I initiators (HR = 1.05, 95% CI: 1.00–1.10). ConclusionsThis head-to-head comparison study estimated comparative MSk risks among different antidiabetic drugs. The risk of MSk conditions among DPP4I initiators were not significantly higher than non-DPP4I initiators.

Efficacy of dulaglutide after switching from incretin-related drugs in patients with type 2 diabetes and inadequate glycemic control.

The efficacy of dulaglutide was assessed according to the pretreatments administered before the initiation of dulaglutide in patients with type 2 diabetes. In total, 89 patients treated using dulaglutide (0.75mg, once a weekly) were investigated. The subjects were divided into the three groups based on the form in which therapy was started: additional therapy (n = 35), switched from dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 32) and switched from daily glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 30). The changes in medication adherence were determined in the daily GLP-1 RAs group using questionnaire surveys. The HbA1c values significantly decreased after the initiation of dulaglutide in all groups (additional therapy group, -1.4 ± 1.6%; DPP-4 inhibitors group, -1.2 ± 1.3%; and daily GLP-1 RAs group, -0.5 ± 0.7%). Forty-six percent of the subjects in the daily GLP-1 RAs group reported that the incidence of forgetting injections of GLP-1 RA was decreased. The reduction of HbA1c was significantly greater in the subjects who reported a decrease in the incidence of forgetting injections (0.9 ± 0.9%) in comparison to those in which there was no change (0.1 ± 0.4%). Dulaglutide is considered effective in patients with type 2 diabetes and inadequate glycemic control, regardless of whether their pretreatment includes daily GLP-1 RA treatment.

Beneficial effects of posttransplant dipeptidyl peptidase-4 inhibitor administration after pancreas transplantation to improve β cell function.

PurposeDipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels and enhance the function of pancreatic β cells. Yet, it is unknown whether posttransplant administration of DPP4 inhibitors is beneficial for pancreas transplant recipients.MethodsWe thus retrospectively analyzed the records of 312 patients who underwent pancreas transplantation between 2000 and 2018 at Asan Medical Center (Seoul, Korea) and compared the metabolic and survival outcomes according to DPP-4 inhibitor treatment.ResultsThe patients were divided into the no DPP-4 inhibitor group (n = 165; no treatment with DPP-4 inhibitors or treated for <1 month) and the DPP-4 inhibitor group (n = 147; treated with DPP-4 inhibitors for ≥1 month). There were no significant differences in levels of glucose, hemoglobin A1c, and insulin between the 2 groups during 36 months of follow-up. However, the level of C-peptide was significantly higher in the DPP-4 inhibitor group at 1, 6, and 24 months posttransplant (all P < 0.05). Moreover, the DPP-4 inhibitor group had significantly higher rates of overall (log-rank test, P = 0.009) and death-censored (log-rank test, P = 0.036) graft survival during a 15-year follow-up.ConclusionPosttransplant DPP-4 inhibitor administration may help improve the clinical outcomes including β cell function after pancreas transplantation.

Cardiovascular Outcomes Comparison of Dipeptidyl Peptidase-4 Inhibitors versus Sulfonylurea as Add-on Therapy for Type 2 Diabetes Mellitus: a Meta-Analysis

ObjectiveRecent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin.MethodsAfter searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected.ResultsRegarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98–1.33; p=0.811; I2=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83–1.27; p=0.517; I2=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53–9.39; p<0.001; I2=98.2 and weighted mean difference, 1.68; 95% CI, 1.07–2.29; p<0.001; I2=94.7, respectively).ConclusionAs add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.

Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study

IntroductionMortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on...

Safety and Efficacy of Four Anti-Diabetic Treatment Regimens in Patients with Type 2 Diabetes during Ramadan fasting: A Comparative Study

Objective: To compare the anti-hyperglycaemic effectiveness and safety of different anti-diabetic treatment regimens in fasting type 2 diabetic subjects during Ramadan. Methods: This was a prospective four-week study of 161 subjects with type 2 diabetes (HbA1c 6.5-8.5%) during Ramadan, at the Department of Endocrinology &amp; Metabolism, Services Hospital, Lahore, Pakistan. Study participants were randomized into four treatment groups: lifestyle modification only (group 1: lifestyle), metformin monotherapy (group 2: Metformin), metformin and sulfonylurea (group 3: Met/SU) and metformin and DPP4 inhibitor (group 4: Met/Sita). Anthropometric and biochemical evaluation were done one week before onset of Ramadan and in the last week of Ramadan. 134 patients completed the study protocol and repeated measures ANOVA was used to compare the groupsfor change inclinical and laboratory parameters from pre-Ramadan baseline. Results: There was a significant decrease in mean blood glucose (mg/dL) and fructosamine(µmol/L)levels post-Ramadan in all treatment groups, with the greatest reduction seen in Met/Sita treatment group [(fructosamine -35.9, p &lt;0.01), mean blood glucose (-23.6, p&lt; 0.05)]. In the safety analysis, Met/Sita group also showed improvement in several metabolic parameters including lipid profile (cholesterol -12.4 mg/dL, p &lt; 0.05; LDL -8.6mg/dL, p &lt;0.05; triglycerides -41.9mg/dL, p &lt;0.05) and transaminases. Only one patient among the study population reported a hypoglycaemic event (Met/SU group). Conclusion: During Ramadan fasting, combination treatment with metformin-sitagliptinin type 2 diabetic subjects resulted in the greatest improvement in glycaemic control without causing hypoglycaemia, and was associated with improvement in lipid profile and hepatic transaminases. Key words: Metformin, sitagliptin, fasting, Ramadan, type 2 diabetes, glucose control

Abstract 311: One-year Outcomes of DPP-4 Inhibitor Treatment in Diabetic Patients After Contemporary Percutaneous Coronary Intervention - Ps Matching from Data of Multicenter Registry -

Introduction: Clinical prognosis in diabetic patients comorbid with coronary artery disease (CAD) remained poor, even in the current drug-eluting stent (DES) era. However, there has been a limited evidence about the prognosis in diabetic patients with CAD who were treated with dipeptidyl peptidase-4 inhibitors (DPP4i). Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent percutaneous coronary intervention (PCI) at 12 hospitals in Japan between 2017 and 2019. Among 1,905 registered patients who were followed up, we ultimately evaluated 615 diabetic patients. They were divided into two groups depending on the prescription of DPP4i at the hospital discharge after the index PCI; DPP4i group (n=287) and Non-DPP4i group (n=328). For the two groups, we performed propensity-score (PS) matching using variables as follows: age, sex, acute coronary syndrome, left ventricular ejection fraction, serum creatinine, insulin use, prescriptions of statin, beta blocker, aspirin, and ACE inhibitor/ARB. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) including death, acute coronary syndrome, stent thrombosis, hospitalization due to heart failure and ischemic stroke. Results: Overall MACCE was observed in 70 patients (11.4%) during 364 days of median observation period. In unmatched patients, Kaplan-Meier analysis showed that patients in the DPP4i group showed a significantly lower MACCE rate than those in the Non-DPP4i group (Log-rank test, p=0.009, Figure A). In 284 PS-matched patients, patients in the DPP4i group still had lower MACCE rate than those in the non-DPP4i group (hazard ratio 0.39, 95% confidence interval 0.16-0.96, p=0.034, Figure B). Conclusion: Propensity-matching analysis showed that hyperglycemia control by DPP4i was associated with better 1-year clinical outcomes in diabetic patients after PCI in the contemporary DES era.

Abstract 14068: One-year Outcomes of Dpp-4 Inhibitor Treatment in Diabetic Patients After Contemporary Percutaneous Coronary Intervention - Ps Matching From Data of Multicenter Registry -

Introduction: Clinical prognosis in diabetic patients comorbid with coronary artery disease (CAD) remained poor, even in the current drug-eluting stent (DES) era. However, there has been a limited evidence about the prognosis in diabetic patients with CAD who were treated with dipeptidyl peptidase-4 inhibitors (DPP4i). Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent percutaneous coronary intervention (PCI) at 12 hospitals in Japan between 2017 and 2019. Among 1,905 registered patients who were followed up, we ultimately evaluated 615 diabetic patients. They were divided into two groups depending on the prescription of DPP4i at the hospital discharge after the index PCI; DPP4i group (n=287) and Non-DPP4i group (n=328). For the two groups, we performed propensity-score (PS) matching using variables as follows: age, sex, acute coronary syndrome, left ventricular ejection fraction, serum creatinine, insulin use, prescriptions of statin, beta blocker, aspirin, and ACE inhibitor/ARB. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) including death, acute coronary syndrome, stent thrombosis, hospitalization due to heart failure and ischemic stroke. Results: Overall MACCE was observed in 70 patients (11.4%) during 364 days of median observation period. In unmatched patients, Kaplan-Meier analysis showed that patients in the DPP4i group showed a significantly lower MACCE rate than those in the Non-DPP4i group (Log-rank test, p=0.009, Figure A). In 284 PS-matched patients, patients in the DPP4i group still had lower MACCE rate than those in the non-DPP4i group (hazard ratio 0.39, 95% confidence interval 0.16-0.96, p=0.034, Figure B). Conclusion: Propensity-matching analysis showed that hyperglycemia control by DPP4i was associated with better 1-year clinical outcomes in diabetic patients after PCI in the contemporary DES era.