Evidence mapPaperPMID 36657986Full record

Trial reportDiabetes care2023

Optimization of Albuminuria-Lowering Treatment in Diabetes by Crossover Rotation to Four Different Drug Classes: A Randomized Crossover Trial.

Viktor Rotbain Curovic, Niels Jongs, Marjolein Y A M Kroonen, Emilie H Zobel, Tine W Hansen, Taha Sen, Gozewijn D Laverman, Adriaan Kooy, Frederik Persson, Peter Rossing and 1 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Guideline
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Combining SGLT2is, GLP1-RAs and nsMRAs in Diabetes: A Scoping Review of Current and Future Perspectives.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Studying and learning.Journal of diabetes · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Viktor Rotbain Curovic1Steno Diabetes Center Copenhagen, Herlev, Denmark.
Niels Jongs2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.
Marjolein Y A M Kroonen2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.
Emilie H Zobel1Steno Diabetes Center Copenhagen, Herlev, Denmark.
Tine W Hansen1Steno Diabetes Center Copenhagen, Herlev, Denmark.
Taha Sen2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.
Gozewijn D Laverman3ZiekenhuisGroep Twente, Almelo, the Netherlands.
Adriaan Kooy4Bethesda Diabetes Research Center, Hoogeveen, the Netherlands.
Frederik Persson1Steno Diabetes Center Copenhagen, Herlev, Denmark.
Peter Rossing1Steno Diabetes Center Copenhagen, Herlev, Denmark.
Hiddo J L Heerspink2Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.ORCID 0000-0002-3126-3730
University of Groningen · NLSteno Diabetes Centers · DKUniversity of Copenhagen · DKZiekenhuis Groep Twente · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveRenin-angiotensin system (RAS) inhibitors decrease the urinary albumin to creatinine ratio (UACR) but are ineffective in up to 40% of patients. We hypothesized that rotation through different drug classes overcomes RAS inhibitor resistance and tested this in a randomized crossover trial. RESEARCH DESIGN AND

methodsWe assigned 26 adults with type 1 diabetes and 37 with type 2 diabetes and UACR between 30 and 500 mg/g and estimated glomerular filtration rate >45 mL/min/1.73 m2 to 4-week treatment periods with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg, and baricitinib 2 mg in random order, separated by 4-week washout periods. Each participant was then re-exposed for 4 weeks to the drug that induced that individual's largest UACR reduction. Primary outcome was the difference in UACR response to the best-performing drug during the confirmation period versus UACR response to the other three drugs.

resultsThere was substantial variation in the best-performing drug. Telmisartan was best performing for 33 participants (52%), empagliflozin and linagliptin in 11 (17%), and baricitinib in 8 participants (13%). The individuals' best-performing drug changed UACR from baseline during the first and confirmatory exposures by a mean of -39.6% (95% CI -44.8, -33.8; P < 0.001) and -22.4% (95% CI -29.7, -12.5; P < 0.001), respectively. The Pearson correlation for first versus confirmatory exposure was 0.39 (P = 0.017). The mean change in UACR with the other three drugs was +1.6% (95% CI -4.3%, 8.0%; P = 0.593 versus baseline; difference versus individuals' best-performing drug at confirmation, 30.9% [95% CI 18.0, 45.3]; P < 0.001).

conclusionsWe demonstrated a large and reproducible variation in participants' responses to different UACR-lowering drug classes. These data support systematic rotation through different drug classes to overcome therapy resistance to RAS inhibition.

Indexed as

Diabetes Mellitus, Type 2AdultAlbuminuriaAzetidinesBenzhydryl CompoundsCreatinineCross-Over StudiesEnzyme InhibitorsGlomerular Filtration RateGlucosidesHumansLinagliptinPurinesPyrazolesRotationSulfonamidesAzetidinesbaricitinibBenzhydryl CompoundsCreatinineempagliflozinEnzyme InhibitorsGlucosidesLinagliptinPurinesPyrazolesSulfonamidesTelmisartan

Identifiers

PMID36657986
PMCPMC10020026
OpenAlexW4317493994

What Socratic holds

Textmetadata
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.