Evidence map›Paper›PMID 22413962›Full record

Trial reportInternational journal of clinical practice2012

Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial.

R R Henry, A V Murray, M H Marmolejo, D Hennicken, A Ptaszynska, J F List

2 registry-linked trialsAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in International journal of clinical practice, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00643851. Cited by 135 papers, 29 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 29 pooled it
20.4field-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.

NCT00643851 phase3completed

A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin as Initial Therapy as Compared With Dapagliflozin Monotherapy and Metformin Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control

Ran2008Enrolled994Registered outcomes6Posted comparisons12ConditionsType 2 DiabetesArmsdapagliflozin, Metformin XR
Open the trial in the graph
NCT02925559 phase4completedstarted 2016, after this paper: background citation

Effect of Anti-diabetic Drugs on Glycemic Variability. A Comparison Between Gliclazide MR (Modified Release) and Dapagliflozin on Glycemic Variability Measured by Continuous Glucose Monitoring (CGM) in Patients With Uncontrolled Type 2 Diabetes

Ran2016Enrolled135Registered outcomes9Posted comparisons0ConditionsDiabetes Mellitus, Type 2Armsdapagliflozin, Gliclazide MR
PMID 22809630PMID 23425012PMID 23170914PMID 23911013PMID 24144654PMID 21816980PMID 22690846PMID 19261490PMID 21813293PMID 16609090PMID 22431673PMID 22446170other papers from this trial
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3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 29 syntheses or guidelines pooled it, 312 citations in OpenAlex.

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  3. Metformin for preventing the progression of chronic kidney disease.The Cochrane database of systematic reviews · 2024 · on this map
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75 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

6 authors at 3 institutions in 3 countries.

R R HenryVA San Diego Healthcare System Research Service and University of California San Diego School of Medicine, San Diego, CA, USA.
A V Murray
M H Marmolejo
D Hennicken
A Ptaszynska
J F List
Bristol-Myers Squibb (Germany) · DEBristol-Myers Squibb (Belgium) · BEUniversity of California, San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCombining metformin (XR) with dapagliflozin to initiate pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c may be advantageous. We conducted two randomised, double-blind, three-arm 24-week trials in treatment-naïve patients to compare dapagliflozin plus metformin, dapagliflozin alone and metformin alone.

methodsEligible patients had baseline HbA1c 7.5-12%. Each trial had three arms: dapagliflozin plus metformin, dapagliflozin monotherapy and metformin monotherapy. Dapagliflozin in combination and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2). Metformin in combination and as monotherapy was titrated to 2000 mg. The primary endpoint was HbA1c change from baseline; secondary endpoints included change in fasting plasma glucose (FPG) and weight.

resultsIn both trials, combination therapy led to significantly greater reductions in HbA1c compared with either monotherapy: -2.05 for dapagliflozin + metformin, -1.19 for dapagliflozin, and -1.35 for metformin (p < 0.0001) (Study 1); -1.98 for dapagliflozin + metformin, -1.45 for dapagliflozin and -1.44 for metformin (p < 0.0001) (Study 2). Combination therapy was statistically superior to monotherapy in reduction of FPG (p < 0.0001 for both studies); combination therapy was more effective than metformin for weight reduction (p < 0.0001). Dapagliflozin 10 mg was non-inferior to metformin in reducing HbA1c (Study 2). Events suggestive of genital infection were reported in 6.7%, 6.9% and 2.0% (Study 1) and 8.5%, 12.8% and 2.4% (Study 2) of patients in combination, dapagliflozin and metformin groups; events suggestive of urinary tract infection were reported in 7.7%, 7.9% and 7.5% (Study 1) and 7.6%, 11.0% and 4.3% (Study 2) of patients in the respective groups. No major hypoglycaemia was reported.

conclusionIn treatment-naïve patients with T2D, dapagliflozin plus metformin was generally well tolerated and effective in reducing HbA1c, FPG and weight. Dapagliflozin-induced glucosuria led to an increase in events suggestive of urinary tract and genital infections.

Indexed as

AdolescentAdultAgedBenzhydryl CompoundsBlood GlucoseBody WeightDiabetes Mellitus, Type 2Double-Blind MethodFemaleGlucosidesGlycated HemoglobinHumansHypoglycemic AgentsMaleMetforminMiddle AgedBenzhydryl CompoundsBlood GlucosedapagliflozinGlucosidesGlycated HemoglobinHypoglycemic AgentsMetformin

Identifiers

PMID22413962
OpenAlexW1953840628

What Socratic holds

Texttitle and abstract
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.