Evidence map›SGLT2 inhibitors × adverse events & safety›PMID 28725912›Full record

SynthesisDiabetologia2017

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

Huilin Tang, Qi Dai, Weilong Shi, Suodi Zhai, Yiqing Song, Jiali Han

Open access · bronzeAbstract readSystematic ReviewNetwork Meta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Diabetologia, 2017. The graph read 4 numbers from its abstract, feeding 1 cell of the map: it finds no clear difference in 1. Cited by 100 papers, 7 of them syntheses that pooled it.

4numbers the graph read from it
1cell of the map it votes in
100citing papers in PubMed, 7 pooled it
11.2field-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.

← favours the treatmentfavours the comparator →
0.10.250.524101 · no effect
Overall cancerSGLT2 inhibitors vs placebo or other active glucose-lowering treatmentsno clear difference · t2dfeeds one cell of the map
OR 1.140.96 to 1.36
When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]).
FeedsSGLT2 inhibitors×adverse events & safety
Bladder cancerSGLT2 inhibitors vs placebo or other active glucose-lowering treatmentsfavours the comparator · t2dfeeds one cell of the map
OR 3.871.48 to 10.1
For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]).

The authors add: the risk of bladder cancer might be increased with SGLT2 inhibitors

FeedsSGLT2 inhibitors×adverse events & safety
Bladder cancerempagliflozin vs placebo or other active glucose-lowering treatmentsfavours the comparator · t2dfeeds one cell of the map
OR 4.491.21 to 16.7
For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]).

The authors add: the risk of bladder cancer might be increased with SGLT2 inhibitors

FeedsSGLT2 inhibitors×adverse events & safety
Gastrointestinal cancerscanagliflozin vs placebo or other active glucose-lowering treatmentsfavours the treatment · t2dfeeds one cell of the map
OR 0.150.04 to 0.60
Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]).

The authors add: canagliflozin might be protective against gastrointestinal cancers

FeedsSGLT2 inhibitors×adverse events & safety

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

SGLT2 inhibitors×adverse events & safety

InconclusiveOpen on the map →What to test next →

38 readable studies in this cell: 18 favour the treatment, 19 find no difference, 1 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 26 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT020991101,233 enrolled · 2014
Δ 1.40-7.40 to 10.1
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27
NCT01649297983 enrolled · 2012
Δ -0.61-0.79 to -0.44
NCT02580591977 enrolled · 2015
Δ -0.28-0.46 to -0.11
NCT02414958730 enrolled · 2015
Δ -0.54-0.66 to -0.41
NCT01381900678 enrolled · 2011
Δ -0.51-0.64 to -0.37
NCT02033889621 enrolled · 2013
Δ 1.50-2.10 to 5.40
NCT02532855614 enrolled · 2015
Δ -2.80-10.7 to 5.10
NCT02630706506 enrolled · 2015
Δ -6.00-16.5 to 4.60
NCT02036515464 enrolled · 2014
Δ -5.70-16.5 to 5.20

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

5 · Its place in the literature

Who cites it

100 citing papers in PubMed, 7 syntheses or guidelines pooled it, 201 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Type 2 diabetes in patients undergoing gastric cancer surgery: areas requiring disease-specific glycemic management.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Huilin TangDepartment of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Qi DaiDepartment of Medicine, School of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA.
Weilong ShiDepartment of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Suodi ZhaiDepartment of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Yiqing SongDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA. yiqsong@iu.edu.
Jiali HanDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA. jialhan@iu.edu.
Indiana University – Purdue University Indianapolis · USPeking University Third Hospital · CNVanderbilt University Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aims/hypothesisThe association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes.

methodsWe systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs.

resultsIn total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). CONCLUSIONS/

interpretationCurrent evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsCanagliflozinDiabetes Mellitus, Type 2GlucosidesHumansHypoglycemic AgentsNeoplasmsRisk FactorsBenzhydryl CompoundsCanagliflozinempagliflozinGlucosidesHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsCancerMeta-analysisRandomised controlled trialsSGLT2 inhibitorsSystematic reviewType 2 diabetes

Identifiers

PMID28725912
OpenAlexW2739126694

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.