scholarly journals The Effects of DPP-4 Inhibitors, GLP-1RAs, and SGLT-2/1 Inhibitors on Heart Failure Outcomes in Diabetic Patients With and Without Heart Failure History: Insights From CVOTs and Drug Mechanism

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaohui Pan ◽  
Shishi Xu ◽  
Juan Li ◽  
Nanwei Tong
Keyword(s):  
Heart Failure ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Drug Mechanism ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes ◽  
History Of ◽  
Glucagon Like Peptide 1 ◽  
Diabetes Drug

Patients with type 2 diabetes (T2D) have a higher risk of heart failure (HF) than healthy people, and the prognosis of patients with diabetes and current or previous HF is worse than that of patients with only diabetes. We reviewed the HF outcomes in recently published cardiovascular outcome trials (CVOTs) of three new classes of anti-diabetic agents, namely, dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like-peptide 1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 inhibitors (SGLT-2is) or SGLT-2 and SGLT-1 dual inhibitors and divided the patients into two groups based on the history of HF (with or without) and analyzed their risks of HHF based on the receipt of the aforementioned anti-diabetes drug types. Since the follow-up period differed among the trials, we expressed the rate of HHF as events/1,000 person-years to describe the HF outcome. At last we pooled the data and analyzed their different effects and mechanisms on heart failure outcomes. Although DPP-4is did not increase the risk of HHF in T2D patients with a history of HF, they were associated with a significantly higher risk of HHF among patients without history of HF. Some GLP-1RAs reduced the risk of macrovascular events, but none of these drugs reduced the risk of HHF in patients with T2D irrespective of their HF history. It was not clarified whether SGLT-1/2is can improve the prognosis of macrovascular events in patients with T2D, but these drugs reduced the risk of HHF regardless of patients’ histories of HF. This information may be useful or referential for the “precise” selection of hyperglycemic medications. Further researches still needed to clarify the mechanisms of these anti-diabetic medications.

scholarly journals Glucose-Lowering Medications and Post-Dementia Survival in Patients with Diabetes and Dementia

2022 ◽  
pp. 1-13
Author(s):  
Juraj Secnik ◽  
Hong Xu ◽  
Emilia Schwertner ◽  
Niklas Hammar ◽  
Michael Alvarsson ◽  
...  
Keyword(s):  
Survival Models ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Intention To Treat ◽  
Dementia Patients ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
All Cause Mortality ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1 ◽  
Using Data

Background: The effectiveness of glucose-lowering drugs (GLDs) is unknown among patients with dementia. Objective: To analyze all-cause mortality among users of six GLDs in dementia and dementia-free subjects, respectively. Methods: This was a longitudinal open-cohort registry-based study using data from the Swedish Dementia Registry, Total Population Register, and four supplemental registers providing data on dementia status, drug usage, confounders, and mortality. The cohort comprised 132,402 subjects with diabetes at baseline, of which 11,401 (8.6%) had dementia and 121,001 (91.4%) were dementia-free. Subsequently, comparable dementia – dementia-free pairs were sampled. Then, as-treated and intention-to-treat exposures to metformin, insulin, sulfonylurea, dipeptidyl-peptidase-4 inhibitors, glucagon-like peptide-1 analogues (GLP-1a), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) were analyzed in the parallel dementia and dementia-free cohorts. Confounding was addressed using inverse-probability weighting and propensity-score matching, and flexible parametric survival models were used to produce hazard ratios (HR) and 95% confidence intervals (CI) of the association between GLDs and all-cause mortality. Results: In the as-treated models, increased mortality was observed among insulin users with dementia (HR 1.34 [95%CI 1.24–1.45]) as well as in dementia-free subjects (1.54 [1.10–1.55]). Conversely, sulfonylurea was associated with higher mortality only in dementia subjects (1.19 [1.01–1.42]). GLP-1a (0.44 [0.25–0.78]) and SGLT-2i users with dementia (0.43 [0.23–0.80]) experienced lower mortality compared to non-users. Conclusion: Insulin and sulfonylurea carried higher mortality risk among dementia patients, while GLP-1a and SGLT-2i were associated with lower risk. GLD-associated mortality varied between dementia and comparable dementia-free subjects. Further studies are needed to optimize GLD use in dementia patients.

P0633EFFECT OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS ON CISPLATIN-INDUCED ACUTE NEPHROTOXICITY IN CANCER PATIENTS WITH DIABETES MELLITUS: A RETROSPECTIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Takamasa Iwakura ◽  
Hirotaka Fukasawa ◽  
Atsushi Kitamura ◽  
Kento Ishibuchi ◽  
Hideo Yasuda ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Kidney Injury ◽  
Dipeptidyl Peptidase ◽  
Cancer Prognosis ◽  
Diabetic Patients ◽  
High Dose ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes ◽  
Egfr Decline

Abstract Background and Aims Cisplatin is a highly effective chemotherapeutic agent. However, acute kidney injury (AKI) limits its subsequent use, resulting in poor cancer prognosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to attenuate cisplatin-induced AKI in animal models, but the effect in human patients remains to be clarified. We hypothesized that DPP-4 inhibitors can prevent cisplatin-induced AKI in diabetic-cancer patients. Method We retrospectively reviewed all consecutive cancer patients who were treated with a first cycle of cisplatin-containing regimen between January 2011 and October 2019. We analysed data of diabetic-cancer patients treated with high-dose cisplatin (> 50 mg/m2)-containing regimens. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the patients treated with DPP-4 inhibitors and those treated without DPP-4 inhibitors. Results A total of 455 patients were treated with cisplatin during the period. Of these, 35 patients were eligible for the analysis. The change of eGFR was significantly less in the patients treated with DPP-4 inhibitors, compared to those without DPP-4 inhibitors [Fig.1; the percentages of eGFR decline (mean ± SD) was 23.6 ± 20.3% vs 41.2 ± 20.6%, respectively; P=0.016]. Furthermore, the incidence of AKI was significantly less in the patients treated with DPP-4 inhibitors (25% vs 60%, respectively; P=0.040). Conclusion DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients. Therefore, the use of DPP-4 inhibitors may be one of supportive therapies for cancer patients treated with high-dose cisplatin.

scholarly journals Postprandial increase in glucagon-like peptide-1 is blunted in severe heart failure

2020 ◽  
Vol 134 (9) ◽  
pp. 1081-1094 ◽  
Author(s):  
Daniel F. Arruda-Junior ◽  
Flavia L. Martins ◽  
Thiago Almeida Salles ◽  
Leonardo Jensen ◽  
Rafael Dariolli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Homeostasis ◽  
Severe Heart Failure ◽  
Diabetic Patients ◽  
Serum Concentrations ◽  
Dipeptidyl Peptidase 4 ◽  
Normal Glucose ◽  
Healthy Control ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.

scholarly journals Modulation of Diabetes by Natural Products and Medicinal Plants via Incretins

Planta Medica ◽  
2019 ◽  
Vol 85 (11/12) ◽  
pp. 825-839 ◽  
Author(s):  
José-Luis Ríos ◽  
Isabel Andújar ◽  
Guillermo R. Schinella ◽  
Flavio Francini
Keyword(s):  
Natural Products ◽  
Medicinal Plants ◽  
Guar Gum ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
New Findings ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

AbstractIncretins are metabolic hormones released after a meal that increase insulin secretion from pancreatic β-cells. The two main incretins are the intestinal peptides glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Both induce a decrease in glycemia, slow down the absorption of nutrients, and are inactivated by the enzyme dipeptidyl peptidase-4. Recently, incretin-based therapies have become a useful tool to treat diabetic patients, and different studies have focused on the identification of glucagon-like peptide-1 receptor agonists, including those of natural origin. This review focuses on the new findings of medicinal plants and natural products as possible active agents on the potentiation of incretin receptor signaling. Among these, soluble fiber from species of Plantago and guar gum show promising effects, iridoid derivatives are relevant activators of incretin receptors, and derivatives of cyanidin, especially diglycosylated ones, are an interesting source of dipeptidyl peptidase-4 inhibitors.

scholarly journals New Antihyperglycemic Drugs and Heart Failure: Synopsis of Basic and Clinical Data

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Dirk von Lewinski ◽  
Ewald Kolesnik ◽  
Markus Wallner ◽  
Michael Resl ◽  
Harald Sourij
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Cardiovascular System ◽  
Clinical Data ◽  
Glucose Transporter ◽  
Meta Analysis ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Glucagon Like Peptide 1

The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors. LEADER, SUSTAIN-6, EMPA-REG OUTCOME, and CANVAS showed potential beneficial results, while the SAVOR-TIMI trial had an increased rate of hospitalization for heart failure. Meanwhile, the same drugs are investigated in preclinical experiments mainly using various animal models, which aim to find interactions and elucidate the underlying downstream mechanisms between the antihyperglycemic drugs and the cardiovascular system. Yet the direct link for observed effects, especially for DPP-4 and SGLT-2 inhibitors, is still unknown. Further inquiry into these mechanisms is crucial for the interpretation of the clinical trials’ outcome and, vice versa, the clinical trials provide hints for an involvement of the cardiovascular system. The synopsis of preclinical and clinical data is essential for a detailed understanding of benefits and risks of new antihyperglycemic drugs.

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