Effect of sodium-glucose cotransporter-2 inhibitors on aldosterone and renin levels in diabetes mellitus type 2 patients: a systematic review and meta-analysis

Abstract

The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels are still inconclusive. This meta-analysis aimed to demonstrate the changes in PAC and PRA levels after the use of SGLT2i in type 2 diabetes patients. A search for relevant publications was performed using PubMed/Medline, Scopus, Cochrane, and Embase databases from their inception through May 2022. Inclusion criteria were studies that contained data on crude PAC and PRA levels before and after the use of SGLT2i in adult type 2 diabetes patients. Standardized mean difference (SMD) with a 95% confidence interval (95% CI) was calculated. Data was separately analyzed by study design: randomized controlled study (RCT) and non-randomized controlled study (non-RCT). Ten studies involving 380 patients were included with two RCT and eight non-RCT. Serum PAC levels showed no significant change after the use of SGLT2i in both RCT and non-RCT. Significantly higher PRA levels were observed after the use of SGLT2i in both RCT and non-RCT with SMD of 0.40 ng/mL/hr; 95% CI (0.06, 0.74) and SMD of 0.36 ng/mL/hr; 95%CI (0.17, 0.55), respectively. Subgroup analysis found significantly higher PRA levels after the use of SGLT2i (SMD 0.45 ng/mL/hr; 95% CI (0.18, 0.71)) only in subgroups that used for three months or less. The use of SGLT2i in diabetes mellitus type 2 patients can affect PRA levels, especially during short-term use. PRA levels should be interpreted with caution in this population.

Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism

“… Abbreviations: ↓, reduced; ↑, increased; ↔, no change; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARR, aldosterone-to-renin ratio; NSAID, nonsteroidal anti-inflammatory drug; MRA, mineralocorticoid receptor antagonist; SGLT2i, sodium-glucose transport protein 2 inhibitor. a SGLT2 inhibitor proposed mechanism: initial increase in osmotic diuresis and natriuresis results in reduction in renal perfusion pressure and sodium load at the distal tubule that can stimulate renin release [ 14 ]. …”

“… a SGLT2 inhibitor proposed mechanism: initial increase in osmotic diuresis and natriuresis results in reduction in renal perfusion pressure and sodium load at the distal tubule that can stimulate renin release [ 14 ]. …”

Effects of 6-month administration of tofogliflozin on cardiac function in elderly patients with heart failure with preserved ejection fraction: A retrospective study of a patient cohort

“…[26] It has also been revealed that administration of SGLT2 inhibitors temporarily exert the renin-angiotensin-aldosterone system (RAA) but recovered within 3 months. [27][28][29] The loss of fluid by SGLT2 is temporary. SGLT2 may have a multimodal effect, including a diuretic effect, protection of the RAA, reduction of blood pressure, and improvement of energy efficiency in the heart.…”

SGLT2 Inhibition and Kidney Potassium Homeostasis

“…As an example, the measurement of plasma renin activity and aldosterone levels after SGLT2is has produced conflicting results and therefore requires additional research for clarification. 41 Future studies should account for the variables affecting the renin-angiotensin-aldosterone axis to include daily Na + intake, an individual's posture at the time of measurement, circadian rhythm, underlying disease state, and dose adjustments in antihypertensive medications. Additional recommended studies should directly measure the comparable changes in interstitial and blood volume to validate whether SGLT2is preferentially reduce interstitial volume.…”