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August 7, 2026npj Metabolic Health and DiseaseOpen Access

Dual SGLT1/2 inhibition with sotagliflozin improves cardiac function and metabolism in type 2 diabetic mice

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Why the study?

Sotagliflozin improves cardiovascular outcomes in patients with diabetes and heart failure, but the metabolic mechanisms underlying these benefits remain incompletely defined.

Does sotagliflozin improve cardiac function and metabolism in a mouse model of type 2 diabetes?

Population

db/db mice as a model of type 2 diabetes

Comparison

Sotagliflozin (5 mg/kg/day) vs untreated

Design

Preclinical animal study

Follow-up

4 weeks

Key result

Sotagliflozin treatment in type 2 diabetic mice improved hyperglycemia, ventricular function, and the cardiac metabolomic profile, despite persistent systemic obesity and insulin resistance.

Authors

MYMegan YoungSDSanushi DambureFCFenn Cullen

Discussion

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Overview

Sotagliflozin effects in diabetic mice do not alter practice; hypothesis-generating for dual SGLT1/2 mechanisms in cardiomyopathy.

Key Points

  • To investigate the effects of sotagliflozin on cardiac function and metabolism in type 2 diabetic mice.
  • Db/db mice received 5 mg/kg/day of sotagliflozin in drinking water for 4 weeks.
  • Cardiac function measured by echocardiography, metabolic profiling via LC-MS/MS and NMR spectroscopy.
  • Susceptibility to ischemia/reperfusion injury assessed in Langendorff-perfused hearts.
  • Sotagliflozin significantly improved hyperglycaemia and ventricular function.
  • Cardiac metabolism showed enhanced glycolytic intermediates and improved bioenergetics.
  • Systemic metabolic abnormalities remained largely unchanged after treatment.

Structured PICO

Does sotagliflozin improve cardiac function and metabolism in a mouse model of type 2 diabetes?

P
Population
40 male mice, including db/db type 2 diabetes models and lean controls, treated for 4 weeks to evaluate cardiac function and metabolism.
I
Intervention
Sotagliflozin 5 mg/kg/day in drinking water for 4 weeks
C
Comparator
Untreated db/db mice and lean controls receiving standard chow and water ad libitum
O
Outcome
Cardiac metabolism (assessed by LC-MS/MS), cardiac function (assessed by echocardiography), and susceptibility to ischemia/reperfusion injury (assessed in Langendorff-perfused hearts)surrogate

Dual SGLT1/2 inhibition with sotagliflozin induces selective cardiac metabolic remodeling and improves ventricular function in diabetic cardiomyopathy independent of global metabolic correction.

Limitations

  • Ketone availability and myocardial ketone utilization were not examined
  • Short treatment duration of 4 weeks
  • Animal model findings may not fully translate to human clinical outcomes

Cite This Study

Young et al. (2026) studied Type 2 diabetes and diabetic cardiomyopathy (n=40). Sotagliflozin vs. Untreated db/db mice was evaluated on Cardiac function and metabolism (echocardiography and metabolomic profiling). Sotagliflozin treatment in type 2 diabetic mice improved hyperglycemia, ventricular function, and the cardiac metabolomic profile, despite persistent systemic obesity and insulin resistance.

synapsesocial.com/papers/6a758be1847ab6d26c01f85ahttps://doi.org/10.1038/s44324-026-00119-z
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