Effects of Sodium-Glucose Cotransporter 2 on Amputation Events: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials

See, Ray Meng; Teo, Yao Neng; Teo, Yao Hao; Syn, Nicholas; Yip, Alicia Swee Yan; Leong, Shariel; Wee, Caitlin Fern; Cheong, Alex Jia Yang; Lee, Chi‐Hang; Chan, Mark Y; Yeo, Tiong Cheng; Wong, Raymond; Chang, Peter; Hong, Choon Chiet; Chai, Ping; Sia, Ching‐Hui

doi:10.1159/000520903

Cited by 13 publications

(7 citation statements)

References 46 publications

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“…There were no obvious differences in amputation events by type of SGLT2 inhibitor, by baseline population, and by duration of SGLT2 inhibitor use [ 148 ].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management

Kang

et al. 2022

Cardiovasc Diabetol

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Type 2 diabetes mellitus (T2DM) is a chronic, complex metabolic disease characterized by chronic hyperglycemia causing from insufficient insulin signaling because of insulin resistance or defective insulin secretion, and may induce severe complications and premature death. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are oral drugs used to reduce hyperglycemia in patients with T2DM, including empagliflozin, ertugliflozin, dapagliflozin and canagliflozin. The primary objective of this article is to examine the clinical benefit, safety, and tolerability of the four SGLT2 inhibitors approved by the US FDA. SGLT2 inhibitors increase urinary glucose excretion via inhibiting SGLT2 to decrease renal reabsorption of filtered glucose and reduce the renal threshold for glucose. Rather than stimulating insulin release, SGLT2 inhibitors improve β-cell function by improving glucotoxicity, as well as reduce insulin resistance and increase insulin sensitivity. Early clinical trials have confirmed the beneficial effects of SGLT2 in T2DM with acceptable safety and excellent tolerability. In recent years, SGLT2 inhibitors has been successively approved by the FDA to decrease cardiovascular death and decrease the risk of stroke and cardiac attack in T2DM adults who have been diagnosed with cardiovascular disease, treating heart failure (HF) with reduced ejection fraction and HF with preserved ejection fraction, and treat diabetic kidney disease (DKD), decrease the risk of hospitalization for HF in T2DM and DKD patients. SGLT2 inhibitors are expected to be an effective treatment for T2DM patients with non alcoholic fatty liver disease. SGLT2 inhibitors have a similar safety profile to placebo or other active control groups, with major adverse events such as Ketoacidosis or hypotension and genital or urinary tract infections.

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“…There were no obvious differences in amputation events by type of SGLT2 inhibitor, by baseline population, and by duration of SGLT2 inhibitor use [ 148 ].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management

Kang

et al. 2022

Cardiovasc Diabetol

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“…People living with diabetes are inherently at elevated risk for LLA events [87,96,97]. Excess amputations were reported in one CVOT and were not replicated across subsequent trials [17,18,21,28,53,98,99]. Everyone with T2DM should be educated regarding the importance of preventative foot care and regular comprehensive assessment of lower limbs must be included in clinical reviews [8,87,96,100].…”

Section: A Step-change In T2dm Management: Bridging the Gap Between G...mentioning

confidence: 99%

“…[ 1 – 4 , 8 , 9 , 11 , 12 , 17 – 40 , 49 , 51 , 53 – 56 , 61 – 66 , 68 – 75 , 83 , 84 , 87 – 89 , 98 – 110 , 121 , 127 – 130 ]…”

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SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

Seidu,

Alabraba,

Davies

et al. 2024

Diabetes Ther

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A substantial evidence base supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in the treatment of type 2 diabetes mellitus (T2DM). This class of medicines has demonstrated important benefits that extend beyond glucose-lowering efficacy to protective mechanisms capable of slowing or preventing the onset of long-term cardiovascular, renal and metabolic (CVRM) complications, making their use highly applicable for organ protection and the maintenance of long-term health outcomes. SGLT2is have shown cost-effectiveness in T2DM management and economic savings over other glucose-lowering therapies due to reduced incidence of cardiovascular and renal events. National and international guidelines advocate SGLT2i use early in the T2DM management pathway, based upon a plethora of supporting data from large-scale cardiovascular outcome trials, renal outcomes trials and real-world studies. While most people with T2DM would benefit from CVRM protection through SGLT2i use, prescribing hesitancy remains, potentially due to confusion concerning their place in the complex therapeutic paradigm, variation in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting. This latest narrative review developed by the Improving Diabetes Steering Committee (IDSC) outlines the place of SGLT2is within current evidence-informed guidelines, examines their potential as the standard of care for the majority of newly diagnosed people with T2DM and sets into context the perceived risks and proven advantages of SGLT2is in terms of sustained health outcomes. The authors discuss the cost-effectiveness case for SGLT2is and provide user-friendly tools to support healthcare professionals in the correct application of these medicines in T2DM management. The previously published IDSC SGLT2i Prescribing Tool for T2DM Management has undergone updates and reformatting and is now available as a Decision Tool in an interactive pdf format as well as an abbreviated printable A4 poster/wall chart. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-024-01550-5.

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“…The higher risk of limb amputations reported in the CANVAS study [ 5 ] raised concern. However, most large studies did not find an increased risk and a recent meta-analysis confirmed no increase in amputations in a combined cohort of 63,716 patients [ 151 ]. This evidence was consistent across different types of SGLT2 inhibitors, baseline populations and lengths of treatment use.…”

Section: Adverse Effectsmentioning

confidence: 99%

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

Chábová

Zakiyanov

2022

IJMS

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Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors’ effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

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Effects of Sodium-Glucose Cotransporter 2 on Amputation Events: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials

Cited by 13 publications

References 46 publications

The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management

The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management

SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

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