Overview
Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney. It is used clinically as an adjunct to diet and exercise, often in combination with other drug therapies, for the management of type 2 diabetes mellitus. The first known inhibitor of SGLTs, phlorizin, was isolated from the bark of apple trees in 1835 and researched extensively into the 20th century, but was ultimately deemed inappropriate for clinical use given its lack of specificity and significant gastrointestinal side effects. Attempts at overcoming these limitations first saw the development of O-glucoside analogs of phlorizin (e.g. remogliflozin etabonate), but these molecules proved relatively pharmacokinetically unstable. The development of C-glucoside phlorizin analogs remedied the issues observed in the previous generation, and led to the FDA approval of canagliflozin in 2013 and both dapagliflozin and empagliflozin in 2014. As the most recently approved of the "flozin" drugs, empagliflozin carries the highest selectivity for SGLT2 over SGLT1 (approximately 2700-fold). Empagliflozin was further approved by the EMA in March 2022 and Health Canada in April 2022, making it the first and only approved treatment in Europe and Canada for adults with symptomatic chronic heart failure regardless of ejection fraction.
Background
Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney. It is used clinically as an adjunct to diet and exercise, often in combination with other drug therapies, for the management of type 2 diabetes mellitus. The first known inhibitor of SGLTs, phlorizin, was isolated from the bark of apple trees in 1835 and researched extensively into the 20th century, but was ultimately deemed inappropriate for clinical use given its lack of specificity and significant gastrointestinal side effects. Attempts at overcoming these limitations first saw the development of O-glucoside analogs of phlorizin (e.g. remogliflozin etabonate), but these molecules proved relatively pharmacokinetically unstable. The development of C-glucoside phlorizin analogs remedied the issues observed in the previous generation, and led to the FDA approval of canagliflozin in 2013 and both dapagliflozin and empagliflozin in 2014. As the most recently approved of the "flozin" drugs, empagliflozin carries the highest selectivity for SGLT2 over SGLT1 (approximately 2700-fold). Empagliflozin was further approved by the EMA in March 2022 and Health Canada in April 2022, making it the first and only approved treatment in Europe and Canada for adults with symptomatic chronic heart failure regardless of ejection fraction.
Indication
Empagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes, either alone or in combination with metformin or linagliptin. It is also indicated to reduce the risk of cardiovascular death in adult patients with both type 2 diabetes mellitus and established cardiovascular disease, either alone or as a combination product with metformin. An extended-release combination product containing empagliflozin, metformin, and linagliptin was approved by the FDA in January 2020 for the improvement of glycemic control in adults with type 2 diabetes mellitus when used adjunctively with diet and exercise. Empagliflozin is also approved to reduce the risk of cardiovascular mortality and hospitalization due to heart failure in adult patients with heart failure, either alone or in combination with metformin. It is also indicated in adults to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression. Empagliflozin is not approved for use in patients with type 1 diabetes.
Associated Conditions
- Cardiovascular Mortality
- Chronic Kidney Disease (CKD)
- End Stage Renal Disease (ESRD)
- Hospitalizations
- Symptomatic Congestive Heart Failure
- Type 2 Diabetes Mellitus
- Decreased estimated glomerular filtration rate
Research Report
Empagliflozin: A Comprehensive Clinical and Pharmacological Profile
I. Introduction and Overview
A. Brief Introduction to Empagliflozin and its Class (SGLT2 Inhibitors)
Empagliflozin is a small molecule drug classified as a Sodium-Glucose Co-transporter 2 (SGLT2) inhibitor.[1] SGLT2 inhibitors represent a significant class of oral antidiabetic medications that exert their therapeutic effects by targeting the SGLT2 proteins predominantly located in the S1 segment of the proximal convoluted tubules of the kidneys.[1] These transporters are responsible for reabsorbing the majority (approximately 90%) of glucose filtered by the glomeruli back into the bloodstream.[1] By selectively inhibiting SGLT2, empagliflozin reduces the renal reabsorption of glucose, consequently lowering the renal threshold for glucose and promoting its excretion in the urine (glucosuria).[1] This mechanism effectively lowers elevated blood glucose levels in patients with type 2 diabetes mellitus (T2DM).
B. Historical Background and Development
The journey leading to the development of SGLT2 inhibitors like empagliflozin began with the discovery of phlorizin in 1835, a naturally occurring glucoside isolated from the bark of apple trees.[1] Phlorizin was identified as an inhibitor of SGLTs, but its clinical utility was hampered by a lack of specificity for SGLT2 over SGLT1 (another SGLT isoform primarily found in the small intestine and to a lesser extent in the S3 segment of the proximal tubule) and significant gastrointestinal side effects.[1] Initial efforts to develop more suitable SGLT inhibitors led to O-glucoside analogs of phlorizin, such as remogliflozin etabonate; however, these compounds proved to be relatively unstable from a pharmacokinetic perspective [User Query].
Clinical Trials
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Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2022/01/10 | Phase 2 | Completed | |||
2022/01/10 | Phase 3 | Recruiting | National Institute of Cardiology, Warsaw, Poland | ||
2021/12/30 | Phase 2 | Active, not recruiting | University Hospital, Basel, Switzerland | ||
2021/12/20 | Phase 4 | Recruiting | Getz Pharma | ||
2021/12/17 | N/A | Completed | |||
2021/12/07 | Phase 4 | Recruiting | |||
2021/12/01 | Phase 4 | Not yet recruiting | |||
2021/12/01 | Phase 2 | Recruiting | |||
2021/12/01 | Phase 3 | Completed | |||
2021/11/23 | Phase 1 | Completed | Genuine Research Center, Egypt |
FDA Drug Approvals
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| No FDA approvals found for this drug. | |||||
EMA Drug Approvals
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HSA Drug Approvals
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NMPA Drug Approvals
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PPB Drug Approvals
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TGA Drug Approvals
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