An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus
Open accessAbstract
Purpose of review: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are the newest class of oral antihyperglycemic agents that have been approved for the treatment of diabetes mellitus. Over the past year, there have been significant developments in both the safety and efficacy of this class of medications that are presented in this review. Recent findings: Apart from data on the glucose-lowering effect of SGLT2 inhibitors, other metabolic benefits have been demonstrated for this class of medications. Moreover, there have been three Food and Drug Administration Drug Safety Communications issued in 2015 that have led to additional drug labeling. The basic mechanism of action, indications, glucose-lowering benefits, other metabolic benefits, and adverse side-effects of SGLT2 inhibitors are presented in this review. Summary: SGLT2 inhibitors are medications that have a unique mechanism of action and that lower glucose independent of insulin. Given the recent findings on efficacy and benefits, these agents are rapidly establishing their role in the treatment of diabetes. Especially in patients with type 2 diabetes not willing or not ready to start insulin, SGLT2 inhibitors may be another option in those patients requiring additional glucose lowering and in those with acceptable risk factor profiles. Although there appears to be some positive benefits in cardiovascular endpoints, more research on the long-term outcomes in people taking SGLT2 inhibitors is warranted.
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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 [75]
The Glucose Control section reports additional HbA1c reduction when SGLT2 inhibitors are added to other medications, including a dapagliflozin study involving patients taking metformin. The Indications for Use section also describes metformin plus an SGLT2 inhibitor as an option, but does not identify patients with cardiovascular or renal disease as those who benefit most; it cautions that the drugs are contraindicated in patients with renal insufficiency below the stated GFR threshold. Page numbers were not available in our copy. (LLM, conf=0.88)
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).”
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 [75]
The Other Metabolic Effects section reports weight loss of approximately 1–4 kg in SGLT2-inhibitor trials, and Indications for Use says the drugs may benefit obese patients because of weight loss. The review concerns treatment of diabetes, so it does not establish the effect for individuals with obesity regardless of diabetes status. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSGLT-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.”
SGLT2 inhibitors lower blood glucose by inhibiting SGLT2 receptors in the proximal tubules of the kidneys and blocking glucose reabsorption from urine.
“Their main mechanism of action is inhibiting SGLT2 receptors in the proximal tubules of the kidneys and thus lowering blood glucose levels by blocking its reabsorption from the urine [8].”
From Neuroprotective effect of SGLT2 inhibitors. (2021) · cites this paper as [8]
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- Authors
- Hsia, D. S., Grove, O., & Cefalu, W. T.
- Affiliations
- Pennington Biomedical Research Center (US)
- Venue
- Current Opinion in Endocrinology, Diabetes & Obesity
- Published
- 2017-02
- Volume
- 24
- Issue
- 1
- Pages
- 73-79
- ISSN
- 1752-296X (ISSN-L)
- 1752-2978
- PMC
- PMC6028052
- OpenAlex
- W2551481457
- Cited by
- 508
- References
- 28
- Citations by year
- 2026: 28 · 2025: 75 · 2024: 78 · 2023: 91 · 2022: 82 · 2021: 69 · 2020: 56 · 2019: 26 · 2018: 1
- FWCI
- 9.05
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Current Opinion in Endocrinology Diabetes and Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (U54GM104940)
- National Center for Complementary and Integrative Health (P50AT002776)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- SGLT2 inhibitors, SGLT2, type 2 diabetes, oral antidiabetic drugs, glucose-lowering effect, insulin-independent glucose lowering, drug safety, adverse effects, cardiovascular outcomes, drug labeling, metabolic benefits
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Benzhydryl Compounds, Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose, Glucosides, Humans, Hypoglycemic Agents, Insulin, Sodium
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