-
1.
Dipeptidyl peptidase-4 inhibitor treatment could decrease Klebsiella pneumoniae pneumonia in patients with type 2 diabetes.
Chen, HH, Chen, CC, Ho, CW, Hsieh, MC, Hsu, SP, Lin, CL, Kao, CH
Postgraduate medicine. 2020;(8):714-719
Abstract
OBJECTIVES To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP4i) for Klebsiella pneumoniae (KP) pneumonia in patients with diabetes. PATIENTS AND METHODS Patients newly diagnosed with type 2 diabetes from 2009 to 2012 were recruited for this population-based and observational study. Diabetes complications severity index (DCSI) score and defined daily dose (DDD) were used for analysis. The multivariable Cox proportional hazards models were used to estimate the risk of KP pneumonia by DPP4i use, with adjustments for propensity score. The Kaplan-Meier method with the log-rank test was used to estimate the risk of KP pneumonia for DPP4i users. RESULTS 34774 patients were included. The incidence rate of KP pneumonia in DDP4i users was 1.51 per 1000 person-years and that for the comparison was 2.25 per 1000 person-years. DDP4i users also had a significantly lower cumulative incidence of KP pneumonia (log-rank test p-value = 0.03). DDP4i users had a significantly lower risk of developing KP pneumonia compared with nonusers (adjusted HR = 0.67, 95% CI = 0.48-0.95). CONCLUSIONS For public health issue with type2 diabetes and infection, DPP4i use decreased KP pneumonia. Male gender, patients with co-morbidities, patients with higher DSCI score and higher DDD of DPP4i were observed to decrease KP pneumonia infection in our analysis. The possible role of DPP4i causing immunological disturbances should be considered.
-
2.
Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study.
Pérez-Belmonte, LM, Torres-Peña, JD, López-Carmona, MD, Ayala-Gutiérrez, MM, Fuentes-Jiménez, F, Jorge Huerta, L, Muñoz, JA, Rubio-Rivas, M, Madrazo, M, Garcia, MG, et al
BMC medicine. 2020;(1):359
Abstract
BACKGROUND Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.
-
3.
Single-pill Combination of Empagliflozin and Linagliptin in Real World Indian Type 2 Diabetes Patient (GRID).
Kovil, R, Saboo, B, Shah, K, Padhye, D, Chudasama, D, Raj, V, Shaikh, N
The Journal of the Association of Physicians of India. 2020;(10):53-55
Abstract
INTRODUCTION For the recently introduced single-pill combination of empagliflozin and linagliptin, real-world evidence has not been available. This observational study aims to assess real-world effectiveness of this combination, in the Indian outpatient setting of type-2 diabetes. METHODS This was a prospective cohort study design, involving patients from 4 centres across western India. Patients with type-2 diabetes and uncontrolled HbA1c, were categorized into 4 groups, including: (1) Naïve to DPP-4i or SGLT-2i; (2) Receiving DPP-4i; (3) Receiving SGLT-2i; (4) Receiving SGLT-2i and DPP-4i as individual pills. Patients were initiated on the fixed-dose combination of empagliflozin + linagliptin, and followed-up over 12-week duration. Clinical parameters of changes in glycaemia, body-weight, and blood-pressure were observed. RESULTS 251 patients were included in the analysis, with just over half of them being males (57%), or having pre-existing cardiovascular disease (54%). The group-wise patient distribution was approximately 47%, 18%,15%, and 20% respectively. The study represented patients across broad range of duration of type-2 diabetes, use of background antidiabetic therapies, and comorbid cardiovascular risk. The use of combination demonstrated significant and clinically meaningful reductions in HbA1c, fasting and postprandial glycaemia levels across all the study groups. Reductions in body-weight and blood-pressure levels were also demonstrated. Interestingly, patients in group 4, who were switched from free drug combination to the fixed-dose combination, also demonstrated significant and meaningful improvements in HbA1c, fasting as well as postprandial glycaemia levels, suggestive of possible improvement in medication-adherence. CONCLUSION This real-world evidence complements the results observed in randomized controlled trials, for meaningful effectiveness with the use of empagliflozin-linagliptin fixed dose combination in the Indian outpatient setting. More evidence may facilitate further characterization of clinical value of this promising combination.
-
4.
Comparative Effectiveness of SGLT2 Inhibitors, GLP-1 Receptor Agonists, DPP-4 Inhibitors, and Sulfonylureas on Risk of Kidney Outcomes: Emulation of a Target Trial Using Health Care Databases.
Xie, Y, Bowe, B, Gibson, AK, McGill, JB, Maddukuri, G, Yan, Y, Al-Aly, Z
Diabetes care. 2020;(11):2859-2869
Abstract
OBJECTIVE To examine the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1), dipeptidyl peptidase 4 inhibitors (DPP-4), and sulfonylureas on risk of kidney outcomes among people with type 2 diabetes. RESEARCH DESIGN AND METHODS U.S. veterans initiated on SGLT2i (n = 18,544), GLP-1 (n = 23,711), DPP-4 (n = 39,399), or sulfonylureas (n = 134,904) were followed for up to 3 years to evaluate the risk of the composite outcome of estimated glomerular filtration rate (eGFR) decline >50%, end-stage kidney disease (ESKD), or all-cause mortality. Risks were estimated using survival models adjusted for predefined covariates as well as covariates identified by a high-dimensional variable selection algorithm through application of generalized propensity scores. RESULTS Compared with those treated with sulfonylureas, treatment with SGLT2i, GLP-1, and DPP-4 was associated with a lower risk of the composite outcome (hazard ratio 0.68 [95% CI 0.63, 0.74], 0.72 [0.67, 0.77], and 0.90 [0.86, 0.95], respectively). While we did not observe a statistically significant difference in risk between the SGLT2i and GLP-1 arms (0.95 [0.87, 1.04]), both SGLT2i and GLP-1 had a lower risk of the composite outcome than DPP-4 (0.76 [0.70, 0.82] and 0.79 [0.74, 0.85], respectively). Analyses by eGFR category suggested that compared with the sulfonylurea arm, those in the SGLT2i and GLP-1 arms exhibited a lower risk of the composite outcome in all eGFR categories, including eGFR <45 mL/min/1.73 m2. Compared with DPP-4, both SGLT2i and GLP-1 exhibited a reduced risk of the composite outcome in eGFR <90 to ≥60, <60 to ≥45, and <45 mL/min/1.73 m2. CONCLUSIONS In type 2 diabetes, treatment with SGLT2i or GLP-1 compared with DPP-4 or sulfonylureas was associated with a lower risk of adverse kidney outcomes.
-
5.
Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors. A case series and analysis of cases reported in the Spanish pharmacovigilance database.
Reolid, A, Muñoz-Aceituno, E, Rodríguez-Jiménez, P, González-Rojano, E, Llamas-Velasco, M, Fraga, J, Daudén, E
International journal of dermatology. 2020;(2):197-206
Abstract
BACKGROUND Bullous pemphigoid (BP) has been associated with dipeptidyl peptidase-4 inhibitors (DPP4i). Clinical features, outcomes, and risk of BP for new DPP4i (linagliptin, saxagliptin, and alopgliptin) are not well established. Comparison of risk of BP appearance for DPP4i and other oral antidiabetic drugs (OADs) such as sodium glucose cotransporter 2 inhibitors has not been studied to date. OBJECTIVES To describe the prevalence, sociodemographic, clinical, and histopathological characteristics, and outcome after drug withdrawal in DPP-4i-associated BP cases from our hospital. To review all Spanish spontaneous notifications of BP where DPP4i or OADs were included as suspected drugs and calculate the reporting odds ratios (RORs). METHODS A retrospective observational study was performed examining the association between DDP4i and BP. Clinical features and RORs were analyzed. Data from the Spanish Pharmacovigilance System (SEFV) are included. RESULTS In our center, 28 of 89 patients with BP (31.5%) were under DPP4i treatment; 53.6% were male, and mean age was 80.8 years. BP debuted the first year after DPP4i in 57.2%. BP control was achieved within 3.7 months after drug withdrawal. Regarding SEFV, 22 of 972 spontaneous notifications were related to BP and DPP4i. RORs were superior for DPP4i compared to other OADs. Vildagliptin had the highest ROR. CONCLUSIONS We present the largest DPP4i-induced BP case series in a single center, with a detailed study of the sociodemographic, clinical, and histopathological characteristics of each patient, and their treatment and outcome. Vildagliptin had the highest risk. DPP4i-associated BP does not seem to have specific clinical characteristics.
-
6.
The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors.
Ling, AW, Chan, CC, Chen, SW, Kao, YW, Huang, CY, Chan, YH, Chu, PH
Cardiovascular diabetology. 2020;(1):188
Abstract
BACKGROUND Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients. METHODS We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. RESULTS Overall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50-0.73; P < 0.001]. Subgroup analysis revealed that the use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i across several subgroups including old age, female in gender, the presence of cardiovascular disease, hemoglobin A1c [Formula: see text] 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i. CONCLUSIONS SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.
-
7.
Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors.
Lee, JY, Cho, Y, Lee, M, Kim, YJ, Lee, YH, Lee, BW, Cha, BS, Kang, ES
Diabetes & metabolism journal. 2019;(2):158-173
Abstract
BACKGROUND We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications. RESULTS After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome. CONCLUSION A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.
-
8.
Risk of amputations associated with SGLT2 inhibitors compared to DPP-4 inhibitors: A propensity-matched cohort study.
Adimadhyam, S, Lee, TA, Calip, GS, Smith Marsh, DE, Layden, BT, Schumock, GT
Diabetes, obesity & metabolism. 2018;(12):2792-2799
Abstract
AIM: To determine the risk of amputations associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i) relative to dipeptidyl peptidase-4 inhibitors (DPP4i). MATERIALS AND METHODS We conducted an active comparator, new user cohort study using data from the Truven Health MarketScan (2009-2015) databases. Patients aged ≥18 years newly initiating SGLT2i or DPP4i between April 1, 2013 and March 31, 2015 were included. Patients were matched 1:1 on high dimensional propensity scores and followed until the earliest of any amputation, treatment discontinuation, disenrollment or end of study period (December 31, 2015). Cox proportional hazards models were used to estimate hazard ratios (HR) and robust 95% confidence intervals (CI) for amputation risk. RESULTS There were 30 216 comparable patients in each arm after matching. Over a median follow-up of 0.6 years, there were 60 amputations (SGLT2i: 36; DPP4i: 24), most at the level of partial foot (75%) and associated with diabetes-related vascular disease (66.7%). The incidence of amputations was higher among SGLT2i patients (1.62 vs. 1.15 per 1000 person-years) with a HR of 1.38 (CI: 0.83-2.31). In subgroup analyses, risk differed by type of SGLT2i: canagliflozin, HR 1.15 (CI: 0.63-2.09); dapagliflozin or empagliflozin, HR 2.25 (CI: 0.78-6.47). CONCLUSION All SGLT2i had an elevated, though not statistically significant, risk for amputations.
-
9.
Novel oral glucose-lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes.
Nyström, T, Bodegard, J, Nathanson, D, Thuresson, M, Norhammar, A, Eriksson, JW
Diabetes, obesity & metabolism. 2017;(6):831-841
-
-
Free full text
-
Abstract
AIMS: To investigate the association of novel oral glucose-lowering drugs (GLDs), compared with that of insulin, with risk of all-cause mortality, cardiovascular disease (CVD) and severe hypoglycaemia. METHODS During 2013 to 2014 all patients with type 2 diabetes in Sweden identified as new users of novel oral GLDs, either dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT2) inhibitors (only dapagliflozin available in Sweden during the study period), with those initiating insulin as a comparison group, in the Prescribed Drug Register were included and followed in the Patient and Cause of Death Registers. The novel GLD group and insulin group were matched 1:1 using propensity score. Cox regression models were used to estimate risks. RESULTS Of 37 603 patients, 21 758 were matched 1:1 to novel GLD vs insulin groups, with median follow-up times of 1.51 years (16 304 patient-years) and 1.53 years (16 306 patient-years), respectively. Treatment with novel GLDs was associated with a 44% (hazard ratio [HR] 0.56 [95% confidence interval {CI} 0.49-0.64]), 15% (HR 0.85 [95% CI 0.73-0.99]) and 74% (0.26 [95% CI 0.12-0.57]) lower risk of all-cause mortality, CVD and hypoglycaemia, respectively, compared with insulin treatment. In separate analyses for the two novel GLDs, dapagliflozin was associated with lower risks of all-cause mortality and CVD (56% [HR 0.44, 95% CI 0.28-0.70] and 49% [HR 0.51, 95% CI 0.30-0.86], respectively), while DPP-4 inhibitor treatment was associated with lower risk of all-cause mortality (41% [HR 0.59, 95% CI 0.51-0.67]), but not with CVD (HR 0.87, 95% CI 0.75-1.01). CONCLUSIONS Novel oral GLD treatment was associated with lower risk of all-cause mortality, CVD and severe hypoglycaemia compared with insulin treatment. Dapagliflozin was associated with a lower risk of both all-cause mortality and CVD, whereas DPP-4 inhibitor treatment was only associated with lower risk of all-cause mortality.
-
10.
Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study.
Tani, S, Nagao, K, Hirayama, A
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2013;(6):443-50
Abstract
BACKGROUND Few data exist as to whether dipeptidyl peptidase (DPP)-4 inhibitors affect cardio-renal interaction, which is a strong independent prognostic factor for cardiovascular disease (CVD), in diabetic patients. We evaluated the effects of a DPP-4 inhibitor on atherogenic low-density lipoprotein (LDL) heterogeneity and albuminuria in diabetics as an indicator of the severity of diabetic nephropathy. METHODS Type 2 diabetes patients (n = 47) inadequately controlled with diabetes therapy were treated with vildagliptin 50 mg bid for 8 weeks. LDL heterogeneity was evaluated on the basis of the patients' small dense (sd) LDL levels and sd-LDL proportion (sd-LDL/LDL cholesterol [LDL-C]). The level of albuminuria was evaluated on the basis of the urinary albumin-to-creatinine ratio (UACR). RESULTS After 8 weeks of treatment, there was no significant change in serum LDL-C level, but the serum sd-LDL level had decreased significantly by 8.8 %, and the UACR had also decreased significantly by 44.6 %. Triglyceride (TG)-metabolism-related markers (TG, remnant-like particle cholesterol, apolipoprotein [apo] B, apoC-2, and apoC-3) had decreased significantly. The Δ (absolute change from baseline) sd-LDL values correlated positively with ΔTG-metabolism-related markers, but not with the Δ hemoglobin (Hb) A1c or Δ fasting blood sugar (ΔFBS). Furthermore, multivariate regression analysis revealed that Δsd-LDL proportion, but not ΔHbA1c or ΔFBS, was an independent predictor of ΔUACR (β = 0.292, p = 0.0016). CONCLUSIONS Although this was a single-arm study, treatment of type 2 diabetes with vildagliptin might prevent the progression of CVD complicating diabetes by improving LDL heterogeneity, and it might improve renal function by decreasing albuminuria. A randomized controlled trial is warranted.