Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician’s Guide
Open accessAbstract
This comprehensive review covers the historical background, physiology, application in type 2 diabetes, novel uses, cardiovascular benefits, side effects and contraindications of sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are an insulin-independent class of oral antihyperglycemic medication that clinicians use in the treatment of type 2 diabetes. Multiple landmark clinical trials support the effectiveness of SGLT2 inhibitors in reducing blood glucose levels, but it is important to understand when to properly utilize them. SGLT2 inhibitors are the most beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease who need further hemoglobin A1c reduction. The novel mechanism of action also demands clinicians be aware of the side effects not typically experienced with other oral antihyperglycemic drugs, such as genital tract infections, lower leg amputations, electrolyte disturbances and bone fractures. On top of their benefits in type 2 diabetes, novel uses for SGLT2 inhibitors are being uncovered. Diabetic patients with non-alcoholic fatty liver disease, who are at an increased risk of cirrhosis and hepatocellular carcinoma, experience a clinically significant reduction in serum alanine aminotransferase levels. SGLT2 inhibitors are also effective at lowering body weight in obese individuals and decreasing systolic blood pressure. Dual SGLT1/SGLT2 inhibitors are currently being investigated as possibly the first oral medication for type 1 diabetes.
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SGLT-2 inhibitors (empagliflozin and dapagliflozin) are most beneficial as adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease that needs further HbA1c reduction.
“Sodium glucosinolate co-transporter 2 (SGLT-2) inhibitors (empagliflozin and dapagliflozin) are the most beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease that needs further HbA1c reduction.”
From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [74]
The Conclusion (page not provided) calls SGLT2 inhibitors useful adjuncts when metformin alone is insufficient, especially for patients with cardiovascular disease. The Monotherapy Vs Combination Therapy section reports additional HbA1c reduction with an SGLT2 inhibitor. The paper also reports cardiovascular and renal benefits of empagliflozin and dapagliflozin, but does not establish that those two drugs are most beneficial specifically for patients with a history of cardiovascular or renal disease who need further HbA1c reduction. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSGLT-2 inhibitors can lower body weight in individuals with obesity.
“SGLT-2 inhibitors can also able to lower the body weight of individuals with obesity (74–76).”
SGLT-2 inhibitors lower the renal glucose threshold and raise urine glucose excretion, thereby lessening hyperglycemia.
“Due to their ability to lower the renal glucose threshold and raise urine glucose excretion, these medicines lessen hyperglycemia.”
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- Authors
- Simes, B. C., & MacGregor, G. G.
- Affiliations
- Alabama College of Osteopathic Medicine (US)
- Corresponding author
- Simes, Bryce C
- MacGregor, Gordon G
- Venue
- Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2019-10
- Volume
- Volume 12
- Pages
- 2125-2136
- ISSN
- 1178-7007 (ISSN-L)
- PMC
- PMC6799898
- OpenAlex
- W2979652934
- Cited by
- 103
- References
- 132
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 18 · 2023: 14 · 2022: 15 · 2021: 14 · 2020: 10
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Diabetes Metabolic Syndrome and Obesity (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- SGLT2 inhibitors, type 2 diabetes, oral antidiabetic drugs, cardiovascular benefits, kidney disease, adverse effects, genital tract infection, lower leg amputation, electrolyte imbalance, bone fractures, non-alcoholic fatty liver disease, weight loss, obesity, systolic blood pressure, type 1 diabetes
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