A review on the medicinal chemistry of sodium glucose co-transporter 2 inhibitors (SGLT2-I): Update from 2010 to present

Ramani, Jonali; Shah, Harshil; Vyas, Vivek K.; Sharma, Manmohan

doi:10.1016/j.ejmcr.2022.100074

Cited by 5 publications

(2 citation statements)

References 124 publications

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“…Odds ratios (95% confidence intervals) (OR 95% CI) were employed as effect estimates. Inconsistency between direct and indirect pooled estimates was evaluated using H statistics, classified as mild (<3), modest (3)(4)(5)(6), or large (>6) [18]. Mixed comparison pooled estimates were estimated using MetaXL© (version 5.3, The Netherlands) and OpenMEE (version 1.0, USA) [19].…”

Section: Study Proceduresmentioning

confidence: 99%

“…SGLT2is function by decreasing glucose reabsorption from the proximal convoluted tubule and increasing urinary glucose excretion [ 6 ]. Consequently, this leads to reduced carbohydrate usage and prompts a shift toward the utilization of fatty acids, resulting in ketogenesis, a process observed as diabetic ketoacidosis (DKA) in diabetic patients [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression

Sridharan,

Sivaramakrishnan

2024

JCM

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Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) represent an emerging class of drugs with diverse indications. Despite their therapeutic potential, concerns regarding safety, particularly diabetic ketoacidosis (DKA), remain contentious, with uncertainty regarding differences among various SGLT2is. This study aimed to conduct a network meta-analysis and meta-regression to evaluate the risk of SGLT2i-induced DKA and associated factors. Methods: We systematically searched electronic databases for randomized clinical trials assessing SGLT2is across indications, reporting incidences of DKA. Mixed treatment comparison pooled estimates (MTCPEs) were calculated, and odds ratios (OR) with 95% confidence intervals (95% CI) served as effect estimates. We analyzed differences across dose categories (low, medium, and high) and conducted a meta-regression analysis to identify risk factors. The strength of evidence for key comparisons was determined. Results: Our analysis included 73 articles encompassing 85,997 participants assessing the risk of DKA. SGLT2is were associated with a heightened risk of DKA compared to placebo/control interventions (OR: 1.83; 95% CI: 1.35, 2.46), a finding confirmed by bootstrap analysis. Among SGLT2is, dapagliflozin (OR: 1.9; 95% CI: 1.17, 3.08), sotagliflozin (OR: 1.93; 95% CI: 1.14, 3.25), canagliflozin (OR: 1.11; 95% CI: 1.11, 12.45), and ertugliflozin (OR: 3.92; 95% CI: 1.04, 14.77) exhibited increased DKA risk. No significant differences were observed among specific SGLT2is. Sub-group analyses revealed a high risk of DKA with low (OR: 1.98; 95% CI: 1.3, 2.95) and high doses (OR: 2.4; 95% CI: 1.7, 3.3), type 1 diabetes (OR: 3.6; 95% CI: 1.6, 8.1), type 2 diabetes (OR: 1.6; 95% CI: 1.3, 2.4), as well as a diabetes duration exceeding 10 years (OR: 3.4; 95% CI: 1.1, 10.8). The evidence of certainty for most comparisons was moderate. Conclusions: SGLT2 inhibitors (SGLT2is) have been found to elevate the risk of DKA. The key factors that significantly predict the likelihood of DKA include the presence of diabetes (whether T1D or T2D) and the duration of diabetes. Based on these findings, standard treatment guidelines should advise taking specific precautions against DKA in patients identified as high-risk.

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Section: Study Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression

Sridharan,

Sivaramakrishnan

2024

JCM

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Bexagliflozin: a comprehensive review of a recently approved SGLT2 inhibitor for the treatment of type 2 diabetes mellitus

Bassett,

Gallo,

et al. 2024

Med Chem Res

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Type 2 diabetes mellitus (T2DM) remains a major global health threat, claiming millions of lives annually. Despite recent advancements in managing T2DM, the need for innovative treatment options persists. Sodium-glucose cotransporter 2 (SGLT2) inhibition has proven to be an effective therapeutic strategy against T2DM, offering benefits in lowering hemoglobin A1c (HbA1c) and plasma glucose levels as well as treatment for patients with diabetes who develop chronic kidney disease (CKD). Bexagliflozin is a recently approved, orally administered SGLT2 inhibitor for treating T2DM and exhibits promise in combating CKD stages 3a and 3b. Structurally, bexagliflozin differs from other SGLT2 inhibitors in that it has a cyclopropyloxyethoxy group at the para position of the peripheral phenyl ring. This review article provides an overview of bexagliflozin’s discovery, mechanism of action, binding site interactions, metabolism, pharmacokinetics, and clinical applications. Emphasis is placed on the significant contribution of SGLT2 inhibitors, particularly bexagliflozin in glycemic control and treating associated comorbidities such as heart failure and chronic kidney disease in T2DM patients.

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SGLT2 inhibitors for the treatment of diabetes: a patent review (2019–23)

Baghel,

Chhikara,

Kumar

et al. 2024

Expert Opinion on Therapeutic Patents

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A review on the medicinal chemistry of sodium glucose co-transporter 2 inhibitors (SGLT2-I): Update from 2010 to present

Cited by 5 publications

References 124 publications

Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression

Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression

Bexagliflozin: a comprehensive review of a recently approved SGLT2 inhibitor for the treatment of type 2 diabetes mellitus

SGLT2 inhibitors for the treatment of diabetes: a patent review (2019–23)

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