SynthesisBMC pharmacology & toxicology2017

Adverse drug events observed in patients with type 2 diabetes mellitus treated with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of published randomized controlled trials.

Pravesh Kumar Bundhun, Girish Janoo, Feng Huang

Full text readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in BMC pharmacology & toxicology, 2017. The graph read 6 numbers from its abstract, feeding 3 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 9 papers, 1 of them a synthesis that pooled it.

6numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
field-weighted citation impact
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.

Read, but not usablea number the graph found but could not read as for or against

Drug discontinuation due to AEs300 mg canagliflozin vs 100 mg canagliflozincomparator not stated · t2dfeeds one cell of the map
OR 1.351.06 to 1.72P = 0.01
However, drug discontinuation due to AEs significantly favored 100 mg canagliflozin only during this unequal follow-up period with OR: 1.35, 95% CI: 1.06-1.72; P = 0.01, but it was not significantly different when trials with similar follow-up periods were analyzed.

The authors add: but it was not significantly different when trials with similar follow-up periods were analyzed

Serious AEs300 mg canagliflozin vs 100 mg canagliflozincomparator not stated · t2dfeeds one cell of the map
OR 1.010.79 to 1.29P = 0.93
The current results showed that serious AEs were not significantly higher in patients who were treated by 300 mg canagliflozin, with OR: 1.01, 95% CI: 0.79-1.29; P = 0.93.
Death300 mg canagliflozin vs 100 mg canagliflozincomparator not stated · t2dfeeds one cell of the map
OR 1.130.43 to 2.94P = 0.80
Also, a similar rate of death was observed in patients who were treated by either 100 or 300 mg canagliflozin with OR: 1.13, 95% CI: 0.43-2.94; P = 0.80.
Hypoglycemia300 mg canagliflozin vs 100 mg canagliflozincomparator not stated · t2dfeeds one cell of the map
OR 0.960.81 to 1.13P = 0.60
Urinary tract infections, postural dizziness and hypoglycemia were also similarly manifested, with OR: 0.93, 95% CI: 0.70-1.23; P = 0.61, OR: 1.51, 95% CI: 0.42-5.37; P = 0.53 and OR: 0.96, 95% CI: 0.81-1.13; P = 0.60 respectively.
Postural dizziness300 mg canagliflozin vs 100 mg canagliflozincomparator not stated · t2dfeeds one cell of the map
OR 1.510.42 to 5.37P = 0.53
Urinary tract infections, postural dizziness and hypoglycemia were also similarly manifested, with OR: 0.93, 95% CI: 0.70-1.23; P = 0.61, OR: 1.51, 95% CI: 0.42-5.37; P = 0.53 and OR: 0.96, 95% CI: 0.81-1.13; P = 0.60 respectively.
Urinary tract infections300 mg canagliflozin vs 100 mg canagliflozincomparator not stated · t2dfeeds one cell of the map
OR 0.930.70 to 1.23P = 0.61
Urinary tract infections, postural dizziness and hypoglycemia were also similarly manifested, with OR: 0.93, 95% CI: 0.70-1.23; P = 0.61, OR: 1.51, 95% CI: 0.42-5.37; P = 0.53 and OR: 0.96, 95% CI: 0.81-1.13; P = 0.60 respectively.

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

No readable resultOpen 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.

SGLT2 inhibitors×all-cause mortality

No readable resultOpen on the map →What to test next →

13 readable studies in this cell: 5 favour the treatment, 6 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 5 families support, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 0.990.83 to 1.18
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86
NCT043636972,401 enrolled · 2020
HR 0.860.68 to 1.08
NCT04157751530 enrolled · 2020
Stratified Win Ratio 1.361.09 to 1.68

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

SGLT2 inhibitors×hypoglycaemia

No readable resultOpen on the map →What to test next →

9 readable studies in this cell: 5 favour the treatment, 4 find no difference, 0 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.900.71 to 1.16
NCT009688121,452 enrolled · 2009
OR 0.100.06 to 0.16
NCT02580591977 enrolled · 2015
IRR 0.940.67 to 1.31
NCT02268214833 enrolled · 2014
OR 3.092.10 to 4.56
NCT02460978815 enrolled · 2015
OR 2.711.81 to 4.06
NCT02414958730 enrolled · 2015
IRR 0.740.52 to 1.07
NCT04233801219 enrolled · 2020
OR 1.760.68 to 4.55

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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

3 authors.

Pravesh Kumar BundhunInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
Girish JanooGuangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
Feng HuangInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China. huangfeng7925@163.com.

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.

backgroundNowadays, canagliflozin monotherapy, or in combination with other oral hypoglycemic agents (OHAs), is often administered in patients who are treated for type 2 diabetes mellitus (T2DM). Therefore, we aimed to systematically compare the adverse drugs events (AEs) which were associated with 100 mg versus 300 mg canagliflozin respectively, using a large number of randomized patients with T2DM which were obtained from published trials.

methodsRandomized controlled trials (RCTs) comparing 100 mg versus 300 mg canagliflozin in patients who were treated for T2DM were searched from electronic databases. AEs reported during a follow up period ranging from 12 to 104 weeks were considered as the clinical endpoints in this analysis. We calculated odds ratios (OR) with 95% confidence intervals (CIs) and the analyses were carried out by RevMan 5 · 3 software.

resultsTen trials involving a total number of 5394 patients (2604 patients who were treated with 100 mg canagliflozin and 2790 patients who were treated with 300 mg canagliflozin) were included. The current results showed that serious AEs were not significantly higher in patients who were treated by 300 mg canagliflozin, with OR: 1.01, 95% CI: 0.79-1.29; P = 0.93. Also, a similar rate of death was observed in patients who were treated by either 100 or 300 mg canagliflozin with OR: 1.13, 95% CI: 0.43-2.94; P = 0.80. Urinary tract infections, postural dizziness and hypoglycemia were also similarly manifested, with OR: 0.93, 95% CI: 0.70-1.23; P = 0.61, OR: 1.51, 95% CI: 0.42-5.37; P = 0.53 and OR: 0.96, 95% CI: 0.81-1.13; P = 0.60 respectively. However, drug discontinuation due to AEs significantly favored 100 mg canagliflozin only during this unequal follow-up period with OR: 1.35, 95% CI: 1.06-1.72; P = 0.01, but it was not significantly different when trials with similar follow-up periods were analyzed.

conclusion300 mg canagliflozin was not associated with significantly higher adverse events compared to 100 mg canagliflozin in those patients who were treated for T2DM. However, because this result was partly affected by other anti-diabetic medications which were included in the treatment regimen, further studies based on patients who were treated strictly on canagliflozin monotherapy should be recommended to completely solve this issue.

Indexed as

Randomized Controlled Trials as TopicCanagliflozinDiabetes Mellitus, Type 2DizzinessDose-Response Relationship, DrugFemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsMaleOdds RatioTreatment OutcomeUrinary Tract InfectionsCanagliflozinGlycated HemoglobinHypoglycemic AgentsAdverse drug eventsCanagliflozinOral hypoglycemic agentsType 2 diabetes mellitus

Identifiers

PMID28411624
PMCPMC5392384

What Socratic holds

Textfull text, public
LicenceCC BY
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.