Effects of sodium–glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta‐analysis of randomized controlled trials

Wu, Bingshu; Zheng, Honghua; Gu, Jianqiu; Guo, Yan; Liu, Yixuan; Wang, Yingfang; Chen, Feng; Yang, Aolin; Wang, Jiabei; Wang, Hailong; Liu, Ying; Wang, Difei

doi:10.1111/jdi.12876

Cited by 9 publications

(8 citation statements)

References 33 publications

(22 reference statements)

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“…Studies have revealed that SGLT‐2 inhibitors could reduce the SUA levels of patients with both T2DM and hyperuricaemia 11,15 . To the best of our knowledge, only a few systematic reviews and meta‐analyses have evaluated the effectiveness of SGLT‐2 inhibitors in reducing the SUA levels of patients with T2DM 10,14,16 . Moreover, no comparative analysis of the effects of different SGLT‐2 inhibitors on lowering SUA levels has been made, let alone the optimal dosage and duration.…”

Section: Discussionmentioning

confidence: 99%

“…Sodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors are a novel class of antidiabetes agents that are independent of insulin release and action 14 . These drugs reduce plasma glucose levels by decreasing the renal reabsorption of glucose and increasing the excretion of urinary glucose 15,16 . In addition, SGLT‐2 inhibitors are characterized by the additional benefits to address unmet clinical needs, such as weight loss, blood pressure control, lipid‐lowering effects and reduced cardiovascular risk factors 15,17–19 .…”

Section: Introductionmentioning

confidence: 99%

“…14 These drugs reduce plasma glucose levels by decreasing the renal reabsorption of glucose and increasing the excretion of urinary glucose. 15,16 In addition, SGLT-2 inhibitors are characterized by the additional benefits to address unmet clinical needs, such as weight loss, blood pressure control, lipid-lowering effects and reduced cardiovascular risk factors. 15,[17][18][19] Notably, growing evidence have revealed that SGLT-2 inhibitors could reduce the SUA levels in patients with T2DM.…”

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confidence: 99%

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Effects of sodium‐glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta‐analysis

Yang

Jia

et al. 2021

Diabetes Obesity Metabolism

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Aims The present study aims to determine the effects of sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors on the serum uric acid (SUA) levels of patients with type 2 diabetes mellitus (T2DM) in Asia. Methods PubMed, CENTRAL, Embase and Cochrane Library databases were searched for randomized controlled trials of SGLT‐2 inhibitors in patients with T2DM up to 15 July 2021, without language or date restrictions. Results In total, 19 high‐quality studies (4218 participants) were included in the present network meta‐analysis. All of the included SGLT‐2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin) significantly decreased SUA levels compared with those of the control [total standard mean difference –0.965, 95% CI (−1.029, −0.901), p = .000, I2 = 98.7%] in patients with T2DM. Subgroup analysis and meta‐regression showed that the combined analysis of different inhibitors might lead to heterogeneity of the results. Therefore, among the SGLT‐2 inhibitors, the results of the subsequent network meta‐analysis revealed that luseogliflozin and dapagliflozin ranked the highest in terms of lowering SUA levels among the SGLT‐2 inhibitors. Moreover, the network meta‐analysis declared that luseogliflozin (1 and 10 mg) and dapagliflozin (5 mg) led to a superior reduction in SUA in patients with T2DM. Conclusions SGLT‐2 inhibitors could significantly reduce SUA levels in patients with T2DM, particularly luseogliflozin (1 and 10 mg) and dapagliflozin (5 mg) possess the best effects. Therefore, SGLT‐2 inhibitors look extremely promising as an antidiabetes treatment option in patients with T2DM with high SUA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of sodium‐glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta‐analysis

Yang

Jia

et al. 2021

Diabetes Obesity Metabolism

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“…Wu et al assessed the impact of SGLT2i as an add-on treatment to insulin therapy compared to the control group in patients with T2DM, which received a placebo in addition to insulin. They calculated MD of SUA change -26.16 μ mol/L (95% CI [-42.14, -10.17], I 2 = 80%) through assessment of 5 comparisons [ 78 ]. Yumo Zhao et al specifically focused on SUA changes of 62 trials, which compared the effects of SGLT2is with placebo or active control or standard care.…”

Section: Discussionmentioning

confidence: 99%

Impacts of Sodium/Glucose Cotransporter-2 Inhibitors on Circulating Uric Acid Concentrations: A Systematic Review and Meta-Analysis

Akbari

Rafiee

Sathyapalan

et al. 2022

Journal of Diabetes Research

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Background. Several trials have assessed the antihyperglycemic effects of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the impact of SGLT2is on serum uric acid (SUA) in patients with T2DM. Methods. Placebo-controlled trials published before 13 August 2021 were identified by searching PubMed, Embase, Web of Science, and Scopus. The intervention group received SGLT2i as monotherapy or add-on treatment, and the control group received a placebo that was replaced with SGLT2i. Clinical trials providing changes in SUA were included. The mean change of SUA, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were calculated (PROSPERO CRD42021287019). Results. After screening of 1172 papers, 59 papers were included in the systematic review. A total of 55 trials (122 groups) of 7 types of SGLT2i on patients with T2DM were eligible for meta-analysis. All SGLT2is significantly decreased SUA levels compared with the placebo groups: empagliflozin mean difference MD = − 40.98 μmol/L, 95% CI [-47.63, -34.32], dapagliflozin MD = − 35.17 μmol/L, 95% CI [-39.68, -30.66], canagliflozin MD = − 36.27 μmol/L, 95% CI [−41.62, −30.93], luseogliflozin MD = − 24.269 μmol/L, 95% CI [-33.31, -15.22], tofogliflozin MD = − 19.47 μmol/L, 95% CI [−27.40, −11.55], and ipragliflozin MD = − 18.85 μmol/L, 95% CI [−27.20, −10.49]. SGLT2i also decreased FPG, body weight, and HbA1c levels. SUA reduction persisted during long-term treatment with SGLT2i (except for empagliflozin), while the SUA reduction was affected by the duration of diabetes. Conclusions. SGLT2i can be a valid therapeutic strategy for patients with T2DM and comorbid hyperuricemia. Besides reducing FPG, body weight, and HbA1c, SGLT2i can significantly decrease SUA levels compared to placebo (Total MD = − 34.07 μmol/L, 95% CI [-37.00, -31.14]).

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“…In a meta‐analysis of randomized control trials that studied the effect of dipeptidyl peptidase‐4 inhibitors in addition to insulin treatment in patients with type 2 diabetes, improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone was reported 9 . In contrast, in a meta‐analysis of randomized control trials that investigated the effect of SGLT2i in addition to insulin treatment on cardiovascular risk factors in patients with type 2 diabetes, better glycemic control and greater reductions of blood pressure, uric acid, bodyweight and daily insulin doses compared with insulin treatment alone were reported 10 . These effects of SGLT2i might provide beneficial effects to suppress cardiovascular events, but the increased risk of hypoglycemia, and urinary tract and genital infection related to SGLT2i should be of note.…”

Section: Impacts Of Newly Developed Insulin Analogsmentioning

confidence: 99%

New perspectives on insulin therapy

Araki

Senokuchi

et al. 2020

J of Diabetes Invest

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Effects of sodium–glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta‐analysis of randomized controlled trials

Abstract: The results showed that in the intervention group, greater reductions were achieved for blood pressure, glucose control, uric acid and bodyweight. This treatment regimen might therefore provide beneficial effects on the occurrence and development of cardiovascular events.

Cited by 9 publications

References 33 publications

Effects of sodium‐glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta‐analysis

Effects of sodium‐glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta‐analysis

Impacts of Sodium/Glucose Cotransporter-2 Inhibitors on Circulating Uric Acid Concentrations: A Systematic Review and Meta-Analysis

New perspectives on insulin therapy

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