Evidence map›Paper›PMID 22492586›Full record

Trial reportDiabetes care2012

Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes.

Julio Rosenstock, Naresh Aggarwal, David Polidori, Yue Zhao, Deborah Arbit, Keith Usiskin, George Capuano, William Canovatchel, Canagliflozin DIA 2001 Study Group

Registry-linked trialOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes care, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02694263 (A Randomised Controlled Trial for People With Established Type 2 Diabetes During Ramadan), which is not on this map. Cited by 170 papers, 26 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed, 26 pooled it
39.0field-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.

NCT02694263 phase4completedstarted 2016, after this paper: background citation

A Randomised Controlled Trial for People With Established Type 2 Diabetes During Ramadan: Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen: The 'Can Do Ramadan' Study

Ran2016Enrolled25Registered outcomes32Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsCanagliflozin, Gliclazide, Glimepiride, Pioglitazone, Repaglinide
PMID 24373063PMID 23564919PMID 26203064PMID 23782529PMID 24026211PMID 23464594PMID 23279307PMID 24073995PMID 16980531PMID 17805082PMID 17925461PMID 18356408other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

170 citing papers in PubMed, 26 syntheses or guidelines pooled it, 418 citations in OpenAlex.

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

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

9 authors at 2 institutions in 1 country.

Julio RosenstockDallas Diabetes and Endocrine Center at Medical City, Dallas, Texas, USA. juliorosenstock@dallasdiabetes.com
Naresh Aggarwal
David Polidori
Yue Zhao
Deborah Arbit
Keith Usiskin
George Capuano
William Canovatchel
Canagliflozin DIA 2001 Study Group
Janssen (United States) · USDallas Diabetes Research Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo evaluate the effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes mellitus inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND

methodsThis was a double-blind, placebo-controlled, parallel-group, multicenter, dose-ranging study in 451 subjects randomized to canagliflozin 50, 100, 200, or 300 mg once daily (QD) or 300 mg twice daily (BID), sitagliptin 100 mg QD, or placebo. Primary end point was change in A1C from baseline through week 12. Secondary end points included change in fasting plasma glucose (FPG), body weight, and overnight urinary glucose-to-creatinine ratio. Safety and tolerability were also assessed.

resultsCanagliflozin was associated with significant reductions in A1C from baseline (7.6-8.0%) to week 12: -0.79, -0.76, -0.70, -0.92, and -0.95% for canagliflozin 50, 100, 200, 300 mg QD and 300 mg BID, respectively, versus -0.22% for placebo (all P < 0.001) and -0.74% for sitagliptin. FPG was reduced by -16 to -27 mg/dL, and body weight was reduced by -2.3 to -3.4%, with significant increases in urinary glucose-to-creatinine ratio. Adverse events were transient, mild to moderate, and balanced across arms except for a non-dose-dependent increase in symptomatic genital infections with canagliflozin (3-8%) versus placebo and sitagliptin (2%). Urinary tract infections were reported without dose dependency in 3-9% of canagliflozin, 6% of placebo, and 2% of sitagliptin arms. Overall incidence of hypoglycemia was low.

conclusionsCanagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss. The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsAdolescentAdultAgedBlood GlucoseCanagliflozinDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDouble-Blind MethodDrug Therapy, CombinationFemaleGlucosidesHumansHypoglycemiaHypoglycemic AgentsMaleBlood GlucoseCanagliflozinGlucosidesHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 InhibitorsThiophenes

Identifiers

PMID22492586
PMCPMC3357223
OpenAlexW2167984652

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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 Socratic graph.