Evidence map›Paper›PMID 25216510›Full record

Trial reportDiabetes care2015

Greater dose-ranging effects on A1C levels than on glucosuria with LX4211, a dual inhibitor of SGLT1 and SGLT2, in patients with type 2 diabetes on metformin monotherapy.

Julio Rosenstock, William T Cefalu, Pablo Lapuerta, Brian Zambrowicz, Ike Ogbaa, Phillip Banks, Arthur Sands

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes care, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 4 pooled it
6.0field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 4 syntheses or guidelines pooled it, 78 citations in OpenAlex.

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  10. A Review of the Potential Role of Sotagliflozin: A Dual SGLT2 and SGLT1 Inhibitor-in the Treatment of Heart Failure.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2024
    Review
  11. Article
  12. SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
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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

7 authors at 3 institutions in 1 country.

Julio RosenstockDallas Diabetes and Endocrine Center at Medical City, Dallas, TX juliorosenstock@dallasdiabetes.com.
William T CefaluPennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA.
Pablo LapuertaLexicon Pharmaceuticals, Inc., The Woodlands, TX.
Brian ZambrowiczLexicon Pharmaceuticals, Inc., The Woodlands, TX.
Ike OgbaaLexicon Pharmaceuticals, Inc., The Woodlands, TX.
Phillip BanksLexicon Pharmaceuticals, Inc., The Woodlands, TX.
Arthur SandsLexicon Pharmaceuticals, Inc., The Woodlands, TX.
Lexicon Pharmaceuticals (United States) · USDallas Diabetes Research Center · USLouisiana State University System · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo assess the dose-ranging efficacy and safety of LX4211, a dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in type 2 diabetes. RESEARCH DESIGN AND

methodsType 2 diabetic patients inadequately controlled on metformin were randomly assigned to 75 mg once daily, 200 mg once daily, 200 mg twice daily, or 400 mg once daily of LX4211 or placebo. Primary end point was A1C change from baseline to week 12. Secondary end points included changes in blood pressure (BP) and body weight.

resultsBaseline characteristics in 299 patients randomly assigned to LX4211 or placebo in this 12-week dose-ranging study were similar: mean age 55.9 years, A1C 8.1% (65 mmol/mol), BMI 33.1 kg/m(2), and BP 124/79 mmHg. LX4211 significantly reduced A1C to week 12 in a dose-dependent manner by 0.42% (4.6 mmol/mol), 0.52% (5.7 mmol/mol), 0.80% (8.7 mmol/mol), and 0.92% (10.0 mmol/mol), respectively (P < 0.001 each), compared with 0.09% (1.0 mmol/mol) for placebo. Greater A1C reductions were produced by 400 mg once a day than 200 mg once a day LX4211 without higher urinary glucose excretion, suggesting a contribution of SGLT1 inhibition. Significant reductions were seen in body weight (-1.85 kg; P < 0.001) and systolic BP (-5.7 mmHg; P < 0.001), but diastolic BP was unchanged (-1.6; P = 0.164). Adverse events with LX4211 were mild to moderate and similar to placebo, including urinary tract infections and gastrointestinal-related events; genital infections were limited to LX4211 groups (0-5.0%). No hypoglycemia occurred.

conclusionsDual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes.

Indexed as

AdultAgedBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Double-Blind MethodDrug Administration ScheduleFemaleGlycated HemoglobinGlycosidesGlycosuriaHumansHypoglycemiaHypoglycemic AgentsMaleMetformin(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triolBlood GlucoseGlycated HemoglobinGlycosidesHypoglycemic AgentsMetforminSodium-Glucose Transporter 1Sodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID25216510
PMCPMC5131876
OpenAlexW2170695489

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

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.