scholarly journals Glucose Lowering Strategies for Cardiac Benefits: Pathophysiological Mechanisms

Physiology ◽  
2018 ◽  
Vol 33 (3) ◽  
pp. 197-210 ◽  
Author(s):  
Harpreet S. Bajaj ◽  
Bernard Zinman
Keyword(s):  
Type 2 Diabetes ◽  
Current Knowledge ◽  
Sglt2 Inhibitors ◽  
Future Research ◽  
Knowledge Gaps ◽  
Glucose Lowering ◽  
Pathophysiological Mechanisms ◽  
Underlying Mechanisms ◽  
Review Current

Recent trials in Type 2 diabetes (T2D) have shown cardiovascular benefits with specific GLP-1 receptor agonists and SGLT2 inhibitors. We discuss the landscape of outcome trials in T2D from a pathophysiology viewpoint, review current knowledge gaps in underlying mechanisms, propose a caloric fuel routing hypothesis, and highlight areas of future research.

scholarly journals Treatment of Patients with Heart failure and Type 2 Diabetes: a review of the literature

2019 ◽  
Vol 13 (4) ◽  
pp. 205-224
Author(s):  
Elisa Fabbri ◽  
Maurizio Nizzoli
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Sglt2 Inhibitors ◽  
New Drugs ◽  
Review Of The Literature ◽  
Glucose Lowering ◽  
Promising Tool ◽  
Patients With Heart Failure ◽  
Underlying Mechanisms

Heart failure (HF) and type 2 diabetes (T2D) often coexist and having both the diseases compared to having one alone is associated with greater challenges in their management/treatment and worse outcomes. The present review of the literature is aimed at providing a comprehensive synopsis of the main evidences about the treatment of the two coexisting conditions. In particular, the recent introduction of new glucose-lowering drugs has been deeply changing the therapeutic approach to T2D. Big randomized controlled trails (RCTs) developed to test the cardiovascular safety of these new drugs consistently highlighted a reduction of the risk of hospitalization for HF in patients with T2D treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors, suggesting a potential and revolutionary class effect probably related to their diuretic effect. Moreover, a renal protective effect of this drug class has also been emerging and the beneficial effect of SGLT2 inhibitors on the risk of HF hospitalization seems to be even greater in patients with worse renal function. In conclusion, although the underlying mechanisms are not fully understood, SGLT2 inhibitors appear to be a promising tool to treat HF and T2D. Ongoing RCTs specifically enrolling patients with HF treated with SGLT2 inhibitors will provide more insights and further information.

scholarly journals Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury

2020 ◽  
Vol 16 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Min Zhao ◽  
Shusen Sun ◽  
Zhenguang Huang ◽  
Tiansheng Wang ◽  
Huilin Tang
Keyword(s):  
Type 2 Diabetes ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Lower Risk ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Event Driven

Background and objectivesLittle is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials.Design, setting, participants, & measurementsWe systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials.ResultsIn the 18 trials with a total of 2051 AKI events (range: 1–300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis.ConclusionsCurrent evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.

scholarly journals Pathophysiological Characteristics Linking Type 2 Diabetes Mellitus and Colorectal Neoplasia

2021 ◽  
pp. 509-522
Author(s):  
Tomas Grega ◽  
Gabriela Vojtechova ◽  
Monika Gregova ◽  
Miroslav Zavoral ◽  
Stepan Suchanek
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Current Knowledge ◽  
Colorectal Neoplasia ◽  
Pathophysiological Mechanisms ◽  
Chronic Hyperglycemia ◽  
Altered Glucose

A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention.

scholarly journals Pharmacoeconomic evaluation of ipragliflozin in combination with metformin in comparison with other regimens of therapy for type 2 diabetes mellitus

2021 ◽  
pp. 50-63
Author(s):  
A. S. Kolbin ◽  
A. A. Kurylev ◽  
Yu. E. Balykina ◽  
M. A. Proskurin
Keyword(s):  
Type 2 Diabetes ◽  
Cost Effectiveness ◽  
Weighted Average ◽  
Sglt2 Inhibitors ◽  
Cost Effectiveness Ratio ◽  
Glucose Lowering ◽  
Lowering Therapy ◽  
Sodium Glucose Cotransporter ◽  
Glucose Lowering Therapy

Ipragliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduce plasma glucose concentrations by inhibiting glucose reabsorption by the kidney through inhibiting SGLT2 sodium-glucose cotransporter and induce glycosuria. SGLT2 inhibitors are a new class of glucose lowering drugs most recently approved for treatment of type 2 diabetes mellitus (T2DM). Unlike other antidiabetic agents, SGLT2 inhibitors improve glycemic control (by HbA1c) and provide multiple additional benefits, including decreased body weight, blood pressure, and other multiple pleiotropic effects. The completed clinical trials and real world data have provided evidence that including of SGLT2 inhibitors in the treatment of T2DM has benefits of reduction of cardiovascular and renal outcomes. Goal. The aim of the study was to conduct a clinical and economic examination of ipragliflozin in comparison with other regimens of glucose-lowering therapy with other SGLT2 inhibitors. Methods. In carrying out the pharmacoeconomic analysis itself, a cost-effectiveness analysis (CEA) was applied with the calculation of the corresponding cost-effectiveness ratio (CER), incremental cost-effectiveness ratio (ICER) according to the formula, as well as an a «budget impact analysis». Multiple one-way sensitivity analysis, check the robustness of the results of the main scenario results to changes in key parameters such as the cost of drugs and complications of diabetes. The time horizon for analyzing the dynamics of economic consequences when using ipragliflozin as a glucose-lowering therapy for T2DM was 5 years. Results. The weighted average cost per patient per year when using the ipragliflozin treatment strategy is 31,182 rubles. The costs of the empagliflozin strategy are 61,291 rubles per patient. In the case of using dapagliflozin, the weighted average costs are 30,032 rubles per patient per year, the total direct medical costs for the current drug therapy option, calculated on the initial number of target practice in 72,143 patients with type 2 diabetes, amounted to 3,068,642,442 rubles. Analysis of the trend of changes in weighted average costs showed that the broader use of ipragliflozin for the treatment of T2DM in the target population leads to reducing in diabetes related direct medical costs by 6.7 %, while the total economic effect of ipragliflozin introduction over five years will be 501,539,327 rubles. Conclusions. Use of ipragliflozin + metformin in T2DM treatment is a cost-effective strategy compared to empagliflozin + metformin. The combination of ipragliflozin with metformin versus dapagliflozin + metformin is economically feasible in terms of cost-effectiveness.

Patient Centered Studies Focusing on Diabetes Self-Management: A Scoping Review

2020 ◽  
Vol 16 (6) ◽  
pp. 557-569
Author(s):  
Monika Salkar ◽  
Meagen Rosenthal ◽  
Tanvee Thakur ◽  
Austin Arnold
Keyword(s):  
Type 2 Diabetes ◽  
Scoping Review ◽  
Diabetes Management ◽  
Current Knowledge ◽  
Future Research ◽  
Patient Centered ◽  
Pubmed Database ◽  
Research Questions ◽  
The Impact

Background: Type 2 diabetes continues to be a significant burden to patients and health systems globally. Addressing this condition from an alternative perspective, patients and various other stakeholders from three northern Mississippi communities co-created patient-centered research questions focused on type 2 diabetes management. Objective: The objective of this scoping review was to explore current literature focusing on nine patient- centered research questions to establish current knowledge and identify future research needs in the area of type 2 diabetes. Methods: A scoping review was conducted to obtain an overview of research related to the study purpose. The PubMed database was searched from March 2013 to March 2018 to identify patient-centered studies focused on type 2 diabetes and relevant to one of the nine research questions. Results: A total of 33 studies were identified and included. For five of the research questions, there was either no previous research literature or only “related” studies could be identified. These largely unexplored topics included how the understanding of guidelines by healthcare providers, specialty, and communication of medication side-effects impact patients’ understanding and outcomes, the impact of improving patients’ preparedness to communicate with providers, and whether younger patients require weight management programs that account for this populations’ needs. Conclusion: This lack of previous literature presents a unique opportunity to partner with patients to conduct this study and help improve the management of type 2 diabetes.

scholarly journals Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Shigeru Toyoda ◽  
Takumi Imai ◽  
Kazuki Shiina ◽  
Hirofumi Tomiyama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Left Ventricular Ejection ◽  
Glucose Lowering

Abstract Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. Methods This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. Results Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. Conclusion The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015

scholarly journals The glucose-lowering therapy structure in special groups of type 2 diabetes mellitus patients based on data from the Moscow region register

2019 ◽  
Vol 22 (3) ◽  
pp. 206-216
Author(s):  
Inna V. Misnikova ◽  
Yulia A. Kovaleva ◽  
Mikhail А. Isakov ◽  
Alexander V. Dreval
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Therapy ◽  
Sglt2 Inhibitors ◽  
Moscow Region ◽  
Glucose Lowering ◽  
Lowering Therapy ◽  
Glucose Lowering Therapy

BACKGROUND: Data of real clinical practice in diabetes mellitus (DM) register allow to evaluate features and trends in structure of glucose-lowering therapy (GLT). AIM: Тo analyze of structure of GLT received by patients with type 2 diabetes mellitus (T2DM) in Moscow region for 2018 and to evaluate its dynamics over 15 years. METHODS: Analysis of GLT structure was carried out on basis of data from register of patients with DM in Moscow region, which is part of National register of diabetes mellitus in Russian Federation. In March 2018 it contained data on 211,792 T2DM patients of Moscow region. Structure of GLT administration was evaluated according T2DM duration, patients age and presence of cardiovascular diseases (CVD). Dynamics of GLT is analyzed from 2004 to 2018 yrs. RESULTS: In 2018 non-insulin glucose-lowering drugs (NIGD) prescription prevailed (78.3%), insulin therapy was prescribed in 18.5% of patients, 3.2% of patients did not receive drug therapy. Most commonly prescribed NIGD were metformin (69.3%) and sulfonylurea (51.3%). Older patients more often than younger did not use GLT at all and less frequently received insulin therapy and iDPP-4. Insulin therapy was prescribed twice as often in patients with CVD compared with patients without CVD (29.6% and 15.5%). NIGD monotherapy has been less commonly used in patients with CVD (67.3% and 81.2%). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) were prescribed to patients with CVD GLP-1 RA in 0.1% of cases, without CVD in 0.3% of cases, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in 1.1% and 0.6%. correspondently. CONCLUSION: Metformin was most commonly prescribed drug in GLT structure for T2DM patients in the Moscow region in 2018 yr. Percentage of new drugs in the structure of GLT increased mainly due to iDPP-4, and secondly due to SGLT2 inhibitors. New classes of GLT were more often prescribed to patients of younger age, with diabetes duration up to 10 years, overweight or obese. Administration of NIGD with proven cardiovascular protection in presence of CVD is almost two times less than for those without CVD.

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