Sodium-Glucose Cotransporter 2 Inhibitors: A Scoping Review of Current Evidence, Mechanisms, and Adverse Effects

Q: What are the key findings of this study?

SGLT2 inhibitors act as highly effective, practice-changing therapies that provide significant cardioprotective and renoprotective benefits for patients with cardiovascular-kidney-metabolic syndrome, regardless of baseline type 2 diabetes status.

Q: What is the clinical evidence from this study?

Study design: Review. Population: Cardiovascular-kidney-metabolic syndrome, type 2 diabetes, congestive heart failure, and chronic kidney disease (n=70000). Intervention: SGLT2 inhibitors vs. Placebo.

Q: What does this research mean for the field?

SGLT2 inhibitors serve as effective, practice-changing therapies for cardiovascular-kidney-metabolic (CKM) syndrome, including congestive heart failure and chronic kidney disease, beyond their original role as hypoglycemic agents for type 2 diabetes. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Sam Woodworth; Robert Hayden

doi:10.56305/001c.171893

October 1, 2026Journal of Brown Hospital MedicineOpen Access

Sodium-Glucose Cotransporter 2 Inhibitors: A Scoping Review of Current Evidence, Mechanisms, and Adverse Effects

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Key result

SGLT2 inhibitors provide robust cardiorenal protection across cardiovascular-kidney-metabolic syndrome, regardless of diabetes status.

n=70,000

Why the study?

SGLT2 inhibitors have evolved from diabetes treatments to key therapies for cardiovascular-kidney-metabolic syndrome, necessitating a comprehensive review of evidence, mechanisms, and adverse effects.

Do SGLT2 inhibitors improve cardiovascular, renal, and metabolic outcomes in patients with cardiovascular-kidney-metabolic syndrome?

Key Points

To review landmark randomized controlled trials assessing the clinical efficacy, mechanisms of action, and adverse effect profile of SGLT2 inhibitors across cardiovascular-kidney-metabolic syndrome.
Synthesized evidence from pivotal randomized controlled trials evaluating SGLT2 inhibitors (including dapagliflozin, empagliflozin, and canagliflozin) in populations with heart failure and chronic kidney disease with or without type 2 diabetes.
Assessed primary composite cardiovascular and renal endpoints, mortality rates, and adverse events including volume depletion, ketoacidosis, and mycotic infections.
In heart failure trials, empagliflozin reduced cardiovascular death or heart failure hospitalization in HFrEF (19.4% vs 24.7%; HR 0.75) and HFpEF (13.8% vs 17.1%; HR 0.79), while dapagliflozin reduced primary composite events in HFmrEF/HFpEF (16.4% vs 19.5%; HR 0.82).
In kidney trials, dapagliflozin reduced renal or cardiovascular outcomes in CKD (9.2% vs 14.5%; HR 0.61), and empagliflozin reduced disease progression or cardiovascular death (13.1% vs 16.9%; HR 0.72).
Reported adverse events included an elevated risk of genital mycotic infections (up to 2.2% vs 0.7%) and rare ketoacidosis (<.5%), with no overall increase in acute kidney injury.

Structured PICO

Do SGLT2 inhibitors improve cardiovascular, renal, and metabolic outcomes in patients with cardiovascular-kidney-metabolic syndrome?

P

Population

A scoping review of pivotal randomized controlled trials including over 70,000 patients evaluating the efficacy and safety of SGLT2 inhibitors across populations with type 2 diabetes, heart failure, and chronic kidney disease.

I

Intervention

SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) as a class

C

Comparator

Placebo (as utilized in the reviewed pivotal trials)

O

Outcome

Composite cardiovascular outcomes (including cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for heart failure) and composite renal outcomes (including progression of CKD, ESKD)composite

SGLT2 inhibitors are a foundational, practice-changing class of medications offering significant cardiorenal protection and reduced hospitalization risk across the spectrum of cardiovascular-kidney-metabolic syndrome.

Limitations

Major pharmaceutical companies sponsored all the reviewed pivotal RCTs
Trial populations were highly selected, limiting generalizability to the complex, heterogeneous patient population routinely encountered in hospital medicine
Patients with severe renal impairment, recent cardiovascular events, or poor outpatient follow-up reliability were often excluded from the original trials

Implication

Supports SGLT2 inhibitor use in CKM syndrome for hospitalists; leaves open optimal implementation and safety monitoring strategies.

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed as oral hypoglycemic agents for type 2 diabetes (T2D), but mounting evidence has solidified their role as practice-changing therapies for cardiovascular-kidney-metabolic (CKM) syndrome, which includes congestive heart failure (CHF) and chronic kidney disease (CKD). This review summarizes the pivotal randomized controlled trials evaluating SGLT2 inhibitors, highlighting their clinical efficacy, key mechanisms of action, and adverse effects. As indications continue to expand and more patients are prescribed SGLT2 inhibitors, hospitalists must have a thorough understanding of this important medication class.

Discussion

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Cite This Study

Woodworth et al. (2026) conducted a review in Cardiovascular-kidney-metabolic syndrome, type 2 diabetes, congestive heart failure, and chronic kidney disease (n=70,000). SGLT2 inhibitors vs. Placebo was evaluated. SGLT2 inhibitors act as highly effective, practice-changing therapies that provide significant cardioprotective and renoprotective benefits for patients with cardiovascular-kidney-metabolic syndrome, regardless of baseline type 2 diabetes status.

synapsesocial.com/papers/6ace6e0db52af824ab02bc72 https://doi.org/10.56305/001c.171893

Topics

HFrEF treatment

Heart failure

SGLT2 inhibitors in heart failure

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Sodium-Glucose Cotransporter 2 Inhibitors: A Scoping Review of Current Evidence, Mechanisms, and Adverse Effects

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Sodium-Glucose Cotransporter 2 Inhibitors: A Scoping Review of Current Evidence, Mechanisms, and Adverse Effects

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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