Trial reportDiabetes, obesity & metabolism2022
Combined sodium glucose co-transporter-2 inhibitor and angiotensin-converting enzyme inhibition upregulates the renin-angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double-blind, placebo-controlled exploratory trial.
Trial report in Diabetes, obesity & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 4 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Safety Profile of SGLT-2 Inhibitors in Older Adults: A Systematic Review and Network Meta-Analysis.Medical sciences (Basel, Switzerland) · 2026Pooled it
- Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.The Cochrane database of systematic reviews · 2024Pooled it
- The efficacy and safety of SGLT2 inhibitors in patients with non-diabetic chronic kidney disease: a systematic review and meta-analysis.International urology and nephrology · 2023Pooled it
- Cardiovascular outcomes and safety of SGLT2 inhibitors in chronic kidney disease patients.Frontiers in endocrinology · 2023Pooled it
- Combined sodium glucose co-transporter-2 inhibitor and angiotensin-converting enzyme inhibition upregulates the renin-angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double-blind, placebo-controlled exploratory trial.Diabetes, obesity & metabolism · 2022Trial
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- Impact of sodium-glucose transport protein-2 (SGLT2) inhibitors on the inflammasome pathway in acute myocardial infarction in type 2 diabetes mellitus: a comprehensive review.Cardiovascular diabetology · 2025Review
- Review
- Angiotensin Dysregulation in Patients with Arterial Aneurysms.International journal of molecular sciences · 2025Article
- Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?Journal of veterinary pharmacology and therapeutics · 2025Review
- Progress of SGLT2 inhibitors in the treatment of common immune-related nephropathies.International urology and nephrology · 2024Review
- New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.International journal of molecular sciences · 2024Review
- Narrative review investigating the nephroprotective mechanisms of sodium glucose cotransporter type 2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease.Frontiers in endocrinology · 2023Review
- Review
- Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention.Cardiovascular diabetology · 2022Article
- The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2022Review
- Does Dapagliflozin influence arterial stiffness and levels of circulating anti-aging hormone soluble Klotho in people with type 2 diabetes and kidney disease? Results of a randomized parallel group clinical trial.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimSodium glucose co-transporter-2 inhibitors (SGLT-2i) improve cardiorenal outcomes in patients with chronic kidney disease (CKD), with and without type 2 diabetes. The molecular mechanisms underlying these pleiotropic effects remain unclear, yet it is speculated that SGLT-2i elicit a neurohormonal modulation resulting in renin-angiotensin system (RAS) activation. We hypothesized that combined SGLT-2 and angiotensin-converting enzyme inhibition (ACEi) favours RAS regulation towards the beneficial angiotensin-(1-7)-driven axis. MATERIALS AND
methodsThis randomized controlled prospective study investigated the effect of 12 weeks treatment with the SGLT-2i empagliflozin on top of ACEi on the molecular RAS dynamics in 24 diabetic and 24 non-diabetic patients with CKD. Systemic RAS peptides were quantified by mass spectrometry.
resultsIn patients with type 2 diabetes, combined SGLT-2i and ACEi significantly upregulated plasma renin activity [pre-treatment median and interquartile range 298.0 (43.0-672.0) pmol/L versus post-treatment 577.0 (95.0-1543.0) pmol/L; p = .037] and angiotensin I levels [pre-treatment 289.0 (42.0-668.0) pmol/L versus post-treatment 573.0 (93.0-1522.0) pmol/L; p = .037], together with a significant increase of angiotensin-(1-7) levels [pre-treatment 14.0 (2.1-19.0) pmol/L versus post-treatment 32.0 (5.7-99.0) pmol/L; p = .012]. Empagliflozin treatment resulted in a 1.5 to 2-fold increase in main RAS peptides in patients with diabetes compared with placebo. No significant effect of empagliflozin on top of ACEi on RAS peptides was found in patients with CKD without diabetes.
conclusionA distinct RAS modulation by SGLT-2i occurs in diabetic kidney disease reflected by enhancement of the beneficial angiotensin-(1-7) providing a molecular background for this renoprotective therapeutic approach.
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