SGLT2-I can be renoprotective for T1DM. Jendle. Lancet

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En tablett, som sänker blodsocker och ges till patienter med typ 2-diabetes, kan även skydda njuren vid typ 1-diabetes. Det visar en ny studie publicerad i Lancet.

– Detta kan bli stort och göra att många ändrar behandlingen. Njursvikt är ett stort problem och orsakar både lidande och stora kostnader, säger Johan Jendle, professor vid Örebro universitet.

 

An oral drug can protect kidneys with type 1 diabetes

A glucose lowering drug commonly used in patients with type 2 diabetes, can protect the kidneys in patients with type 1 diabetes. According to results shown in a new study published in the Lancet.

“This can be huge and cause many to switch treatments. Chronic kidney failure is a major problem, leading to both suffering and high costs,” says Johan Jendle, professor at Örebro University.

Johan Jendle.

Johan Jendle standing in a hallway at Campus in Örebro University, professor of medical science

 

A glucose lowering drug for oral administration and commonly used in patients with type 2 diabetes, can protect the kidneys in patients with type 1 diabetes. According to results shown in a new study published in the Lancet.

“This can be huge and cause many to switch treatments. Kidney failure is a major problem, causes both suffering and high costs,” says Johan Jendle, professor at Örebro University.

Link to article in The Lancet Diabetes & Endocrinology

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30280-1/fulltext

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30280-1/fulltext

“But further studies are needed to confirm these findings,” adds Johan Jendle.

Dapagliflozin has shown to protect the kidneys in patients with type 2 diabetes and researchers want to find out if it has the same effect in subjects with type 1 diabetes.

The study included two hundred fifty-one patients with type 1 diabetes and with increased levels of protein in the urine. The patients were divided into three groups: one group received a placebo, another received a low dose of the drug, 5 mg, and the third received a slightly higher dose, 10 mg, of dapagliflozin.Researchers then compared the protein levels in the patients’ urine.

“We examined the kidneys’ ability to filter. High blood sugar and high blood pressure make the kidney vulnerable and unable to cope. I usually compare with a coffee filter that breaks – the grounds then pass through into the coffee. We don’t want the protein to pass through into the urine,” explains Johan Jendle.

In the group receiving the lower dose, protein levels in the urine decreased by 13% and on the higher dose 31% respectively.

“In addition, secondary effects were low,” says Johan Jendle.

A serious side effect of the class of drugs to which dapagliflozin belongs to is an elevated risk of increased ketone bodies, in the blood. Ketones are a sign of acute insulin deficiency and can lead to ketoacidosis. None of the patients in the placebo group developed this condition. Of the patients taking a low dose of dapagliflozin, one per cent were found to have ketones in their blood while four per cent in the group receiving the higher dose.

In the study, three per cent in the placebo group, and five respective six per cent receiving low or high dose of dapagliflozin developed a common genital infection. Researchers also saw an increase in urinary tract infections in patients taking the drug.

“These side-effects are in line with what has previously been reported in patients with type 2 diabetes. And even if the numbers are low, the aim is to use a dose as low as possible to avoid possible side effects. For the first time we have a study that indicates that adjunctive therapy to insulin is associated with a reduced risk of kidney complications," says Johan Jendle.

Since kidney protection was not a pre-specified endpoint in the study but based on previously collected data, the next step is to conduct a so-called prospective randomized clinical trial to confirm the results.

Facts

In type 1 diabetes, the body is unable to produce insulin, leading to too much glucose in the blood. Although type 1 diabetes is a life-long disease, effective treatment is available.

In type 2 diabetes, the body has difficulty keeping the blood sugar levels normal. Common symptoms include fatigue and increased urine volumes. Symptoms often develop slowly and can sometimes be difficult to observe. You can act by lifestyle changes to lower your glucose levels, but you will need glucose lowering medication.

Chronic kidney disease can affect almost every part of your body. Potential complications may include: Fluid retention, which could lead to swelling in your arms and legs and accumulation of toxic substances. 

Text Linda Harradine

https://www.oru.se/nyheter/ny-studie-visar-att-tablett-kan-skydda-njuren-vid-typ-1-diabetes/ 

Press release Örebro Universitet

 

ARTICLES| VOLUME 8, ISSUE 10, P845-854, OCTOBER 01, 2020

Effect of dapagliflozin as an adjunct to insulin over 52 weeks in individuals with type 1 diabetes: post-hoc renal analysis of the DEPICT randomised controlled trials
 

ABSTRACT

Summary

Background

The DEPICT-1 and DEPICT-2 studies showed that dapagliflozin as an adjunct to insulin in individuals with inadequately controlled type 1 diabetes improved glycaemic control and bodyweight, without increase in risk of hypoglycaemia. We aimed to determine the effect of dapagliflozin on urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) using pooled data from the DEPICT studies.

Methods

In this post-hoc analysis, we used data pooled from both DEPICT studies (DEPICT-1 ran from Nov 11, 2014, to Aug 25, 2017; DEPICT-2 ran from July 8, 2015, to April 18, 2018), in which participants were aged 18–75 years, with inadequately controlled type 1 diabetes and with a baseline UACR of at least 30 mg/g. In the DEPICT studies, participants were randomly assigned (1:1:1) to receive dapagliflozin (5 mg or 10 mg) or placebo all plus insulin, for 24 weeks, with a 28-week long-term extension (ie, 52 weeks in total). In this post-hoc analysis, we assessed the percentage change from baseline in UACR and in eGFR, up to 52 weeks. UACR, eGFR, and safety were assessed in all eligible participants who had received at least one dose of study drug. HbA 1c, bodyweight, and systolic blood pressure were assessed in all participants who received at least one dose of study drug during the first 24-week period, and who had a baseline and any post-baseline assessment for that parameter. The DEPICT trials were registered with ClinicalTrials.gov, NCT02268214 (DEPICT-1), NCT02460978 (DEPICT-2), and are now complete.

Results

251 participants with albuminuria at baseline were included in this post-hoc analysis; of whom 80 (32%) had been randomly assigned to dapagliflozin 5 mg, 84 (33%) to dapagliflozin 10 mg, and 87 (35%) to placebo. Compared with placebo, treatment with both dapagliflozin doses improved UACR over 52 weeks. At week 52, mean difference in change from baseline versus placebo in UACR was −13·3% (95% CI −37·2 to 19·8) for dapagliflozin 5 mg and −31·1% (−49·9 to −5·2) for dapagliflozin 10 mg. No notable change from baseline was seen in eGFR, with a mean difference in change from baseline versus placebo of 3·27 mL/min per 1·73 m 2 (95% CI −0·92 to 7·45) for dapagliflozin 5 mg and 2·12 mL/min per 1·73 m 2 (–2·03 to 6·27) for dapagliflozin 10 mg. Similar proportions of participants in each treatment group had adverse events and serious adverse events, including hypoglycaemia and diabetic ketoacidosis; no new safety signals were identified in this population.

Interpretation

Treatment with dapagliflozin resulted in UACR reduction, which might provide renoprotective benefits in individuals with type 1 diabetes and albuminuria. Dedicated prospective studies are needed to confirm these findings as prespecified endpoints.

Funding AstraZeneca.

 

 

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