Evidence map›Paper›PMID 27316632›Full record

Trial reportDiabetologia2016

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes.

David Cherney, Søren S Lund, Bruce A Perkins, Per-Henrik Groop, Mark E Cooper, Stefan Kaspers, Egon Pfarr, Hans J Woerle, Maximilian von Eynatten

4 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 85 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 11 pooled it
23.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

NCT01159600 phase3completednot on this map

A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg, 25 mg) Administered Orally, Once Daily Over 24 Weeks in Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control Despite Treatment With Metformin Alone or Metformin in Combination With a Sulfonylurea

TypeinterventionalSponsorBoehringer IngelheimRan2010Enrolled1,504ConditionsDiabetes Mellitus, Type 2ArmsPlacebo identical to BI 10773 high dose, Placebo identical to BI 10773 low dose, BI 10773
NCT01164501 phase3completednot on this map

A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg and 25 mg Administered Once Daily) as Add on to Pre-existing Antidiabetic Therapy Over 52 Weeks in Patients With Type 2 Diabetes Mellitus and Renal Impairment and Insufficient Glycaemic Control

TypeinterventionalSponsorBoehringer IngelheimRan2010 to 2012Enrolled741ConditionsDiabetes Mellitus, Type 2, Renal InsufficiencyArmsBI 10773, Placebo
NCT01177813 phase3completednot on this map

A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 10773 and Sitagliptin Administered Orally Over 24 Weeks, in Drug naïve Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control Despite Diet and Exercise

TypeinterventionalSponsorBoehringer IngelheimRan2010Enrolled986ConditionsDiabetes Mellitus, Type 2ArmsPlacebo identical to BI10773 high dose, BI 10773, BI 10773 open label, Placebo identical to BI10773 low dose, Placebo identical to Sitagliptin 100mg
NCT01210001 phase3completednot on this map

A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Trial of BI 10773 (10 and 25 mg Administered Orally Once Daily) Over 24 Weeks in Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control Despite a Background Therapy of Pioglitazone Alone or in Combination With Metformin

TypeinterventionalSponsorBoehringer IngelheimRan2010Enrolled499ConditionsDiabetes Mellitus, Type 2ArmsPlacebo, BI 10773
3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 11 syntheses or guidelines pooled it, 172 citations in OpenAlex.

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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 4 countries.

David CherneyToronto General Hospital, 585 University Ave, 8N-845, Toronto, ON, Canada, M5G 2N2. david.cherney@uhn.ca.
Søren S LundBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Bruce A PerkinsMount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
Per-Henrik GroopAbdominal Centre Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Mark E CooperBaker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
Stefan KaspersBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Egon PfarrBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Hans J WoerleBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Maximilian von EynattenBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Boehringer Ingelheim (Germany) · DEBaker Heart and Diabetes Institute · AUFolkhälsans Forskningscentrum · FIToronto General Hospital · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisSodium glucose cotransporter 2 (SGLT2) inhibition lowers HbA1c, systolic BP (SBP) and weight in patients with type 2 diabetes and reduces renal hyperfiltration associated with type 1 diabetes, suggesting decreased intraglomerular hypertension. As lowering HbA1c, SBP, weight and intraglomerular pressure is associated with anti-albuminuric effects in diabetes, we hypothesised that SGLT2 inhibition would reduce the urine albumin-to-creatinine ratio (UACR) to a clinically meaningful extent.

methodsWe examined the effect of the SGLT2 inhibitor empagliflozin on UACR by pooling data from patients with type 2 diabetes and prevalent microalbuminuria (UACR = 30-300 mg/g; n = 636) or macroalbuminuria (UACR > 300 mg/g; n = 215) who participated in one of five phase III randomised clinical trials. Primary assessment was defined as percentage change in geometric mean UACR from baseline to week 24.

resultsAfter controlling for clinical confounders including baseline log-transformed UACR, HbA1c, SBP and estimated GFR (according to the Modification of Diet in Renal Disease [MDRD] formula), treatment with empagliflozin significantly reduced UACR in patients with microalbuminuria (-32% vs placebo; p < 0.001) or macroalbuminuria (-41% vs placebo; p < 0.001). Intriguingly, in regression models, most of the UACR-lowering effect with empagliflozin was not explained by SGLT2 inhibition-related improvements in HbA1c, SBP or weight. CONCLUSIONS/

interpretationIn patients with type 2 diabetes and either micro- or macroalbuminuria, empagliflozin reduced UACR by a clinically meaningful amount. This effect was largely independent of the known metabolic or systemic haemodynamic effects of this drug class. Our results further support a direct renal effect of SGLT2 inhibitors. Prospective studies are needed to explore the potential of this intervention to alter the course of kidney disease in high-risk patients with diabetes.

trial registrationClinicaltrials.gov NCT01177813 (study 1); NCT01159600 (study 2); NCT01159600 (study 3); NCT01210001 (study 4); and NCT01164501 (study 5).

Indexed as

Sodium-Glucose Transporter 2 InhibitorsAgedAlbuminuriaBenzhydryl CompoundsBlood GlucoseBlood PressureDiabetes Mellitus, Type 2FemaleGlomerular Filtration RateGlucosidesGlycated HemoglobinHumansHypoglycemic AgentsMaleMiddle AgedSodium-Glucose Transporter 2Benzhydryl CompoundsBlood GlucoseempagliflozinGlucosidesGlycated HemoglobinHypoglycemic AgentsSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsEmpagliflozinMacroalbuminuriaMicroalbuminuriaSodium glucose cotransporter 2Type 2 diabetesUrine albumin-to-creatinine ratio

Identifiers

PMID27316632
OpenAlexW2425017047

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.