pf-04971729 and dapagliflozin

To evaluate dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin according to their effect on the glycated hemoglobin A1c (HbA1c) level in patients with type 2 diabetes mellitus.. The Web of Science, PubMed, Cochrane Library, EMBASE, and Clinical Trials databases were electronically searched to collect randomized controlled trials of patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used to perform the meta-analysis and to create plots.. Finally, 27 studies were selected and included in this study. The meta-analysis results showed that sodium-dependent glucose transporter (SGLT) inhibitors significantly reduced the HbA1c level in patients with type 2 diabetes mellitus. However, these results were highly heterogeneous, so we conducted a subgroup analysis. The results of the subgroup analysis suggested that by dividing populations into different subgroups, the heterogeneity of each group could be reduced.. SGLT inhibitors had a good effect on the HbA1c level in patients with type 2 diabetes mellitus, but there might be differences in the efficacy of SGLT inhibitors in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations.. CRD42020185025.

Topics: Benzhydryl Compounds; Blood Glucose; Bridged Bicyclo Compounds, Heterocyclic; Canagliflozin; Diabetes Mellitus, Type 2; Glucosides; Glycated Hemoglobin; Glycosides; Humans; Sodium-Glucose Transporter 2 Inhibitors; Time Factors

The sodium glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin represent a novel class of medications to manage type 2 diabetes through urinary excretion of glucose. These drugs block glucose reabsorption by the kidneys to increase glucosuria. These drugs provide hemoglobin A1C reduction, promote weight loss, and remain hypoglycemic-neutral when not used in combination with insulin or secretagogues. Canagliflozin and empagliflozin have shown cardiovascular benefit. The potential to reduce the risk of cardiovascular death in patients with type 2 diabetes, along with the benefit of weight reduction, makes these new agents useful tools for the primary care provider.

Topics: Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Canagliflozin; Diabetes Mellitus, Type 2; Glucose; Glucosides; Glycated Hemoglobin; Glycosuria; Humans; Hypoglycemic Agents; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Weight Loss

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP.. We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP. We searched all studies published before August 17, 2016, which reported 24-hour ambulatory BP data. Mean differences in 24-hour BP, daytime BP, and nighttime BP were calculated by a random-effects model. SGLT2 inhibitors significantly reduce 24-hour ambulatory systolic and diastolic BP by -3.76 mm Hg (95% CI, -4.23 to -2.34; I. This meta-analysis shows that the reduction in 24-hour ambulatory BP observed with SGLT2 inhibitors is a class effect. The diurnal effect of SGLT2 inhibitors on 24-hour ambulatory BP may contribute to their favorable effects on cardiovascular outcomes.

Topics: Adult; Aged; Benzhydryl Compounds; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Bridged Bicyclo Compounds, Heterocyclic; Canagliflozin; Circadian Rhythm; Diabetes Mellitus; Female; Glucosides; Humans; Hypoglycemic Agents; Kidney Tubules, Proximal; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

This study evaluated the characteristics of new users of sodium glucose co-transporter 2 inhibitors (SGLT2i) in clinical practice to assess the applicability of the findings from clinical trials (Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial, Canagliflozin Cardiovascular Assessment Study (CANVAS) program and the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS-CV) trial) and multinational observational studies (CVD-REAL Nordic study and CVD-REAL 2 study).. We conducted a retrospective cohort study using the largest electronic medical records database from seven hospitals in Taiwan. We included adult patients with type 2 diabetes initiating canagliflozin, dapagliflozin and empagliflozin between 1 January 2018 and 31 August 2019. We compared the patient characteristics with SGLT2i to examine the data representativeness of clinical trials and to evaluate channeling uses between canagliflozin, dapagliflozin and empagliflozin.. We identified a cohort of 11 650 patients newly initiating SGLT2i, 49.9% of whom received empagliflozin. However, only 18.7%, 19.2%, 50.4% and 57.3% of real-world SGLT2i new users were included in the EMPA-REG OUTCOME trial, VERTIS-CV trial, DECLARE-TIMI 58 trial and CANVAS program, respectively. Reasons for exclusion were largely reduced cardiovascular disease risks in real-world patients, namely 72.8%, 73.6% and 34.2% for EMPA-REG OUTCOME trial, VERTIS-CV trial and DECLARE-TIMI 58 trial and CANVAS program, respectively. However, hemoglobin A1c out of range accounted for the most frequent reason (25.0%) for exclusion of real-world patients from the CANVAS program. We found channeling uses in different SGLT2i, for example, more patients receiving empagliflozin (15.3%) and canagliflozin (19.6%) had poorer renal functions (eg, estimated glomerular filtration rate <60 mL/min/1.73 m. The findings provide clear evidence that results from current studies may be less applicable to real-world patients. Further studies are required to support the concept of real-world cardiovascular event protection through SGLT2i.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Blood Glucose; Bridged Bicyclo Compounds, Heterocyclic; Canagliflozin; Cardiovascular Diseases; Clinical Trials as Topic; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glucosides; Glycated Hemoglobin; Humans; Male; Middle Aged; Observational Studies as Topic; Practice Patterns, Physicians'; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors