Influence of Dapagliflozin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Li, Fengfei; Gu, Ganyu; Li, Qian; Zhu, Hong-Hong; Su, Xiaofei; Wu, Jindan; Ye, Lei; Ma, Jianhua

doi:10.1155/2016/5347262

Cited by 27 publications

(35 citation statements)

References 39 publications

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“…14,15 Dapagliflozin is an orally administered, potent and selective inhibitor of SGLT2 that significantly reduces blood glucose levels and improves glycaemic variability. 16 Dapagliflozin is approved for the treatment of T2DM and has been shown to improve glycaemic control, stabilize insulin dosages and reduce body weight with low rates of hypoglycaemia. [17][18][19][20][21][22] When assessing dapagliflozin in patients with T1DM, the pharmacokinetic profile is dose-dependent and similar across Japanese 23 and Caucasian 24 patients.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT‐5): 52‐week results from a randomized, open‐label, phase III clinical trial

Araki

Watada

Uchigata

et al. 2019

Diabetes Obesity Metabolism

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Aims To investigate the safety and tolerability of 5 and 10 mg dapagliflozin added to insulin therapy over 52 weeks in Japanese patients with inadequately controlled type 1 diabetes mellitus (T1DM). Materials and methods This randomized, open‐label, parallel‐group, multicentre phase III clinical trial was conducted from October 26, 2015 to June 15, 2017. The primary endpoint was the occurrence of adverse events such as hypoglycaemia and diabetic ketoacidosis. Secondary endpoints included changes in glycaemic parameters, total daily insulin dosage and body weight over time. The efficacy of dapagliflozin in patients stratified by body mass index (BMI) <25.0 and ≥25.0 kg/m2 was evaluated in a subgroup analysis. Results In total, 151 patients received 5 mg (n = 76) or 10 mg (n = 75) dapagliflozin once daily for 52 weeks. Adverse events were observed in 88.2% and 73.3% of patients in the 5 and 10 mg dapagliflozin groups, respectively. Severe hypoglycaemia was reported in 2.6% (n = 2) and 6.7% (n = 5) of patients, and diabetic ketoacidosis in 2.6% (n = 2) and 1.3% (n = 1) of patients in the 5 and 10 mg dapagliflozin groups, respectively. The adjusted mean (95% confidence interval) changes in glycated haemoglobin at week 52 were −0.33% (−0.50, −0.15) and −0.36% (−0.53, −0.18) in the 5 and 10 mg dapagliflozin groups, respectively. There were no differences in efficacy parameters when stratified by BMI. Conclusions This study demonstrated the long‐term safety and tolerability of dapagliflozin added to insulin therapy in Japanese patients with inadequately controlled T1DM.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT‐5): 52‐week results from a randomized, open‐label, phase III clinical trial

Araki

Watada

Uchigata

et al. 2019

Diabetes Obesity Metabolism

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“…In diabetes, oxidative stress plays a key role in favouring the appearance of cardiovascular complications (21). In patients with type 2 diabetes, dapagli ozin reduced glucose variability as well as oxidative stress (22), while it has been reported in an animal model of diabetes that empagli ozin can reduce oxidative stress generation (23). Therefore, although not detected in our analyses, we believe that the role of reducing HbA1c variability in the bene cial effects of empagli ozin on cardiovascular death remains to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Long-Term HbA1c Variability and Cardiovascular Death: Insights from the EMPA-REG OUTCOME Trial

Ceriello¹,

Ap²,

Zwiener³

et al. 2020

Preprint

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Background: Glucose variability has been associated with cardiovascular (CV) outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and CV death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of CV death by 38%. We explore post-hoc the association between HbA1c variability and CV death, and the potential mediating effects of HbA1c variability on empagliflozin’s CV death reductions.Methods: In total, 7,020 patients with type 2 diabetes and established CV disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between CV death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment.Results: HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for CV death in both treatment arms with no interaction with treatment.Conclusions: HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of CV death. Empagliflozin’s reduction in CV death did not appear to be mediated by reductions in HbA1c variability.ClinicalTrials.gov number, NCT01131676. Registered May 27 2010. https://clinicaltrials.gov/ct2/show/NCT01131676

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“…Clinical studies showed a beneficial effect of dapagliflozin monotherapy on the reduction of diurnal glycaemic variability, assessed as the mean amplitude of glucose fluctuations, and the reduction of oxidative stress, assessed by plasma 8-prostaglandin F2a levels [17]. It was also found in 4 week-observation that dapagliflozin in combination with metformin or with insulin reduces the mean amplitude of glucose fluctuations by 10 mg/dL, whereas in patients receiving placebo in combination with metformin or with insulin, the mean fluctuation amplitude increased by 5.3 mg/dL [18].…”

Section: Hyperglycaemia and Diurnal Variations Of Blood Glucosementioning

confidence: 99%

The impact of dapagliflozin on cardiovascular system in the course of type 2 diabetes mellitus

Stelmaszyk

Dworacka

2017

Clinical Diabetology

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Influence of Dapagliflozin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Cited by 27 publications

References 39 publications

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT‐5): 52‐week results from a randomized, open‐label, phase III clinical trial

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT‐5): 52‐week results from a randomized, open‐label, phase III clinical trial

Long-Term HbA1c Variability and Cardiovascular Death: Insights from the EMPA-REG OUTCOME Trial

The impact of dapagliflozin on cardiovascular system in the course of type 2 diabetes mellitus

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