Efficacy and safety of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: A meta‑analysis of randomized controlled trials

Huang, Yuxin; Jiang, Zeju; Wei, Yiping

doi:10.3892/etm.2021.9813

Cited by 14 publications

(17 citation statements)

References 36 publications

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“…Furthermore, Van et al summarized that dapagliflozin had shown promising results as an adjunct therapy in T1DM patients, leading to better glucose control, weight loss and lower blood pressure 17 . In addition, Huang et al reported that dapagliflozin as an adjuvant drug for insulin therapy in T1DM patients could provide a significant benefit, 21 improving adverse cardiovascular outcomes and bodyweight 10,11 . Of course, some adverse effects, such as the risk of diabetic ketoacidosis and hypoglycaemia, were of particular interest, especially in the T1DM patients.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Huang et al reported that dapagliflozin as an adjuvant drug for insulin therapy in T1DM patients could provide a significant benefit,21 improving adverse cardiovascular outcomes and bodyweight 10,11. Of course, some adverse effects, such as the risk of diabetic ketoacidosis and hypoglycaemia, were of particular interest, especially in the T1DM patients.…”

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confidence: 99%

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Quantifying the relationship between dapagliflozin and loss of weight in type 1 diabetes mellitus patients

Wang

Han

et al. 2021

Clinical Pharmacy Therapeu

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What is known and objectives: Dapagliflozin was the first oral treatment approved in type 1 diabetes mellitus (T1DM) patients, simultaneously improving body weight.However, the time course and dose effect of dapagliflozin on loss of weight in T1DM patients was still unknown. The present study aimed to investigate quantitative relationship between dapagliflozin and loss of weight in T1DM patients based on Modelbased Meta-analysis.Methods: Five dapagliflozin dosage groups, two of them were 5 mg/day and three of them were 10 mg/day, 1612 T1DM patients were analysed with maximal effect (E max ) model, and evaluation index was change rate of body weight from baseline value.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantifying the relationship between dapagliflozin and loss of weight in type 1 diabetes mellitus patients

Wang

Han

et al. 2021

Clinical Pharmacy Therapeu

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“…Most studies have evaluated the effect of SGLT2 inhibitors on Type 2 DM but few have assessed their effects on Type 1 DM [14][15][16][17][18][19]; also, their effects on cardiovascular diseases are still unclear in Type 1 DM in both clinical and experimental scenarios. In Type 1 DM, the main mechanism responsible for cardiomyopathy is related to the decreased insulin signaling [20].…”

Section: Introductionmentioning

confidence: 99%

“…Most studies have evaluated the effect of SGLT2 inhibitors on Type 2 DM, but few have assessed their effects on Type 1 DM [14][15][16][17][18][19]; also, their effects on cardiovascular diseases are still unclear in Type 1 DM in both clinical and experimental scenarios. In this study we evaluated the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

et al. 2022

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Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C, n = 14); control treated with dapagliflozin (C + DAPA, n = 14); diabetes (DM, n = 20); and diabetes treated with dapagliflozin (DM + DAPA, n = 20) for 8 weeks. Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or Kruskal–Wallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM (C 507 ± 52; C + DAPA 474 ± 50; DM 381 ± 52 *; DM + DAPA 430 ± 48 # g; * p < 0.05 vs. C; # p < 0.05 vs. C + DAPA and DM + DAPA). DM echocardiogram presented left ventricular and left atrium dilation with impaired systolic and diastolic function. Cardiac changes were attenuated by dapagliflozin. Myocardial hydroxyproline concentration and interstitial collagen fraction did not differ between groups. The expression of Type III collagen was lower in DM and DM + DAPA than their controls. Type I collagen expression and Type I-to-III collagen ratio were lower in DM + DAPA than C + DAPA. DM + DAPA had lower lipid hydroperoxide concentration (C 275 ± 42; C + DAPA 299 ± 50; DM 385 ± 54 *; DM + DAPA 304 ± 40 # nmol/g tissue; * p < 0.05 vs. C; # p < 0.05 vs. DM) and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.

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“…Similarly, the pooled analysis of DEPICT-1 and DEPICT-2 studies found an increased onset of diabetic ketoacidosis with dapagliflozin compared with placebo over 52 weeks [ 40 ]. However, a recent meta-analysis of randomized controlled clinical trials seem to find that the short-term use (24 weeks) of dapagliflozin associated with insulin for T1DM was not associated with an increased risk of diabetic ketoacidosis, but as highlighted by Authors additional high-quality studies are needed to determine its long-term safety [ 41 ]. However, the risk of ketoacidosis associated SGLT2 inhibitors has led over the years to recommendations for the management of this event in patients with T1DM [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

The Reporting Frequency of Ketoacidosis Events with Dapagliflozin from the European Spontaneous Reporting System: The DAPA-KETO Study

et al. 2022

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Dapagliflozin was associated with an increased risk of diabetic ketoacidosis that has led to the European withdrawal of the authorization for the type 1 diabetes. However, it is still used for the treatment of type 2 diabetes. Therefore, we aim to evaluate the occurrence of dapagliflozin-induced ketoacidosis events by using the European spontaneous reporting system. The reporting odds ratios (ROR) were computed to assess the reporting frequency of ketoacidosis events for dapagliflozin compared to Dipeptidyl peptidase-4 (DPP-4) inhibitors, insulins, or all other Sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A total of 2406 cases with dapagliflozin reported at least one event of ketoacidosis. The three most reported events were: diabetic ketoacidosis (1412; 55.39%), ketoacidosis (476; 18.67%), and euglycaemic diabetic ketoacidosis (296; 11.61%). Dapagliflozin was associated with the higher reporting frequency of ketoacidosis events compared to DPP-4 inhibitors (ROR 12.07, 95%CI 11.67–13.81) or insulins (ROR 7.59, 95%CI 7.13–7.89). A lower reporting frequency was instead observed compared to other SGLT2 inhibitors (ROR 0.91, 95%CI 0.87–0.96). Considering the higher reporting frequency of ketoacidosis observed with dapagliflozin then DPP-4 inhibitors or insulins, attention should be given to patients treated with this drug.

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Efficacy and safety of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: A meta‑analysis of randomized controlled trials

Cited by 14 publications

References 36 publications

Quantifying the relationship between dapagliflozin and loss of weight in type 1 diabetes mellitus patients

Quantifying the relationship between dapagliflozin and loss of weight in type 1 diabetes mellitus patients

Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

The Reporting Frequency of Ketoacidosis Events with Dapagliflozin from the European Spontaneous Reporting System: The DAPA-KETO Study

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