Dataset Information

Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

ABSTRACT:

Background

The syndrome of inappropriate antidiuresis (SIAD) is characterized by a reduction of free water excretion with consecutive hypotonic hyponatremia and is therefore challenging to treat. The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion, likely leading to increased electrolyte free water clearance.

Methods

In this randomized, double-blind, placebo-controlled, crossover trial, we compared 4-week treatment with empagliflozin 25 mg/d to placebo in outpatients with chronic SIAD-induced hyponatremia. At baseline and after both treatment cycles, patients underwent different assessments including neurocognitive testing (Montreal Cognitive Assessment [MoCA]). The primary end point was the difference in serum sodium levels between treatments.

Results

Fourteen patients, 50% female, with a median age of 72 years (interquartile range [IQR], 65-77), completed the trial. Median serum sodium level at baseline was 131 mmol/L (IQR, 130-132). After treatment with empagliflozin, median serum sodium level rose to 134 mmol/L (IQR, 132-136), whereas no increase was seen with placebo (130 mmol/L; IQR, 128-132), corresponding to a serum sodium increase of 4.1 mmol/L (95% confidence interval [CI], 1.7 to 6.5; P =0.004). Exploratory analyses showed that treatment with empagliflozin led to improved neurocognitive function with an increase of 1.16 (95% CI, 0.05 to 2.26) in the MoCA score. Treatment was well tolerated; no serious adverse events were reported.

Conclusion

The SGLT2 inhibitor empagliflozin is a promising new treatment option for chronic SIAD-induced hyponatremia, possibly improving neurocognitive function. Larger studies are needed to confirm the observed treatment effects.

Clinical trial registration number

ClinicalTrials.gov NCT03202667.

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SUBMITTER: Refardt J

PROVIDER: S-EPMC10103093 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

Refardt Julie J Imber Cornelia C Nobbenhuis Rianne R Sailer Clara O CO Haslbauer Aaron A Monnerat Sophie S Bathelt Cemile C Vogt Deborah R DR Berres Manfred M Winzeler Bettina B Bridenbaugh Stephanie A SA Christ-Crain Mirjam M

Journal of the American Society of Nephrology : JASN 20221117 2

<h4>Background</h4>The syndrome of inappropriate antidiuresis (SIAD) is characterized by a reduction of free water excretion with consecutive hypotonic hyponatremia and is therefore challenging to treat. The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion, likely leading to increased electrolyte free water clearance.<h4>Methods</h4>In this randomized, double-blind, placebo-controlled, crossover trial, we compared 4-week treat ...[more]

PMID: 36396331

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Project description:IntroductionPostprandial hypoglycaemia after gastric bypass surgery (also known as postbariatric hypoglycaemia or PBH) is an increasingly encountered clinical problem. PBH is characterised by meal-induced rapid spikes and consequent falls in glycaemia, resulting in both hypoglycaemia burden and high glycaemic variability. Despite its frequency, there is currently no approved pharmacotherapy. The purpose of this investigation is to evaluate efficacy and safety of empagliflozin 25 mg, a sodium-glucose cotransporter 2-inhibitor, to reduce glucose excursions and hypoglycaemia burden in patients with PBH after gastric bypass surgery.Methods and analysisIn a prospective, single-centre, randomised, double-blind, placebo-controlled, crossover trial, we plan to enrol 22 adults (≥18 years) with PBH after Roux-en-Y gastric bypass surgery (plasma or sensor glucose <3.0 mmol/L). Eligible patients will be randomised to receive empagliflozin 25 mg and placebo once daily, each for 20 days, in random order. Study periods will be separated by a 2-6 weeks wash-out period. The primary efficacy outcome will be the amplitude of plasma glucose excursion (peak to nadir) during a mixed meal tolerance test. Results will be presented as paired-differences±SD plus 95% CIs with p values and hypothesis testing for primary and secondary outcomes according to intention-to-treat. Secondary outcomes include continuous glucose monitoring-based outcomes, further metabolic measures and safety.Ethics and disseminationThe DEEP-EMPA trial (original protocol title: Randomized, double-blind, placebo-controlled crossover trialassessing the impact of the SGLT2 inhibitor empagliflozin onpostprandial hypoglycaemia after gastric bypass) was approved by the Bern Ethics Committee (ID 2021-01187) and Swissmedic (Ref. Number: 102663190) in October and November 2021, respectively. First results are expected in the first quarter of 2023 and will be disseminated via peer-reviewed publications and presented at national and international conferences. The acronym DEEP was derived from an overarching project title (DEciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia after Bariatric Surgery), the term EMPA stands for the drug empagliflozin.Trial registration numberNCT05057819.

Project description:IntroductionKidney stones are a global healthcare problem. Given high recurrence rates and the morbidity associated with symptomatic stone disease, effective medical prophylaxis is clearly an unmet need. Explanatory analyses of randomised controlled trials with sodium/glucose cotransporter isoform 2 inhibitors indicated a 30%-50% reduced rate of stone events in patients with diabetes. Underlying mechanisms remain unclear. We aim to determine the effect of empagliflozin on urinary supersaturations in non-diabetic kidney stone formers to evaluate their therapeutic potential for recurrence prevention. We will provide first clinical trial evidence on whether urinary supersaturations are affected by empagliflozin in kidney stone formers.Methods and analysisThe SWEETSTONE trial is a randomised, double-blind, placebo-controlled, cross-over, exploratory study to assess the impact of empagliflozin on urinary supersaturations of calcium oxalate, calcium phosphate and uric acid in kidney stone formers. We plan to include 46 non-diabetic adults (18-74 years) with ≥1 past kidney stone event and stone composition with ≥80% of calcium or ≥80% of uric acid. Patients with secondary causes of kidney stones or chronic kidney disease will be excluded. Eligible individuals will be randomised in equal proportions to receive either a 14-day treatment with 25 mg empagliflozin followed after the 2-6 weeks wash out period by a 14-day treatment with a matching placebo or the reverse procedure. Secondary outcomes will include electrolyte concentrations, renal function, mineral metabolism and glycaemic parameters, urinary volume and safety.Results will be presented as effect measures (95% CIs) with p values and hypothesis testing for primary outcomes (significance level 0.02).Ethics and disseminationThe SWEETSTONE trial was approved by the Swiss ethics committee and Swissmedic. First results are expected in the fourth quarter of 2022.Trial registration numberNCT04911660; Pre-results.

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Dataset Information

Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

Background

Methods

Results

Conclusion

Clinical trial registration number

Podcast

Publications

Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

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