Evidence map›Paper›PMID 25791290›Full record

SynthesisThe lancet. Diabetes & endocrinology2015

Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials.

Jacob A Udell, Matthew A Cavender, Deepak L Bhatt, Saurav Chatterjee, Michael E Farkouh, Benjamin M Scirica

Registry-linked trialAbstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in The lancet. Diabetes & endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04183868 (Comparative Effects of Empagliflozin Versus Glimepiride After 26-weeks of Treatment Add on Metformin on Myocardial Metabolic Rate of Glucose Estimated Through 18FDG-PET in Patients With Type 2 Diabetes), which is not on this map. Cited by 95 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 8 pooled it
26.4field-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.

NCT04183868 phase4completedstarted 2016, after this paper: background citation

Comparative Effects of Empagliflozin Versus Glimepiride After 26-weeks of Treatment Add on Metformin on Myocardial Metabolic Rate of Glucose Estimated Through 18FDG-PET in Patients With Type 2 Diabetes

Ran2016Enrolled26Registered outcomes10Posted comparisons0ConditionsCardiovascular Risk Factor, Type 2 DiabetesArmsempagliflozin 10 mg, Glimepiride 2 mg
PMID 24929430PMID 24463454PMID 26378978PMID 26343814PMID 26052984PMID 25537706PMID 25271206PMID 23404920PMID 22357182PMID 21606218PMID 11511119PMID 9742976other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 8 syntheses or guidelines pooled it, 248 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2019
    Guideline
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Trial
  10. Review
  11. Article
  12. Protective Effect ofCurrent issues in molecular biology · 2026
    Article
  13. Review
  14. Review
  15. Review
  16. Impact of Sitagliptin on Neprilysin and Glycemic Control in Newly Diagnosed Type 2 Diabetes Patients.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Article
  17. Article
  18. Review
  19. Roles of non-coding RNA in diabetic cardiomyopathy.Cardiovascular diabetology · 2024
    Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Jacob A UdellWomen's College Research Institute and Cardiovascular Division, Department of Medicine, Women's College Hospital, Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, University Health Network, Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada. Electronic address: jay.udell@utoronto.ca.
Matthew A CavenderCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Deepak L BhattCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Saurav ChatterjeeDivision of Cardiology, St Luke's-Roosevelt Hospital, Mount Sinai Health System, New York, NY, USA.
Michael E FarkouhPeter Munk Cardiac Centre, University Health Network, Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada.
Benjamin M SciricaCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Harvard University · USHeart and Stroke Foundation · CAUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundSome glucose-lowering drugs or strategies adversely affect cardiovascular outcomes. We aimed to assess the extent to which glucose lowering by various drugs or strategies increases the risk of heart failure in patients with or at risk for type 2 diabetes, and to establish whether risk is associated with achieved differences in glycaemia or weight control.

methodsWe searched Ovid Medline, the Cochrane Library, and meeting abstracts up to Feb 20, 2015, for large randomised controlled trials of glucose-lowering drugs or strategies that assessed cardiovascular outcomes. The primary endpoint was incidence of heart failure. We derived pooled risk ratios (RRs) with random-effects models.

findingsWe included data from 14 trials, with mean duration 4·3 (2·3) years, comprising 95 502 patients, of whom 3907 (4%) patients developed a heart failure event. Glucose-lowering drugs or strategies were associated with a 0·50% (SD 0·33) reduction in HbA1c and a 1·7 kg (2·8) weight gain. Overall, glucose-lowering drugs or strategies increased the risk of heart failure compared with standard care (RR 1·14, 95% CI 1·01-1·30; p=0·041). The magnitude of this effect varied dependent on the method of glucose lowering (p for interaction=0·00021). Across drug classes, risk was highest with peroxisome proliferator-activated receptor agonists (RR 1·42, 95% CI 1·15-1·76; six trials), intermediate with dipeptidyl peptidase-4 inhibitors (1·25, 1·08-1·45; two trials), and neutral with insulin glargine (0·90, 0·77-1·05; one trial). Target-based intensive glycaemic control strategies (RR 1·00, 95% CI 0·88-1·13; four trials) and intensive weight loss (0·80, 95% CI 0·62-1·04; one trial) were also not associated with development of heart failure. Meta-regression analysis showed that for every 1·0 kg of weight gain associated with glucose-lowering drugs or strategies, there was a 7·1% (95% CI 1·0-13·6) relative increase in the risk of heart failure compared with standard care (p=0·022).

interpretationCompared with standard care, glycaemic lowering by various drugs or strategies might increase the risk of heart failure, with the magnitude of risk dependent on the method of glucose lowering and, potentially, weight gain.

fundingNone.

Indexed as

AgedDiabetes Mellitus, Type 2Heart FailureHumansHypoglycemic AgentsMiddle AgedRandomized Controlled Trials as TopicRisk FactorsHypoglycemic Agents

Identifiers

PMID25791290
OpenAlexW2007374852

What OpenQuestion 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 OpenQuestion graph.