Evidence map›Paper›PMID 25352655›Full record

Trial reportDiabetes care2015

Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin.

Julio Rosenstock, Lars Hansen, Pamela Zee, Yan Li, William Cook, Boaz Hirshberg, Nayyar Iqbal

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetes care, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01606007. Cited by 114 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 21 pooled it
30.0field-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.

NCT01606007 phase3completed

A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Add-On Therapy With Saxagliptin and Dapagliflozin Added to Metformin Compared to Add-On Therapy With Saxagliptin in Combination With Metformin or Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone.

Ran2012Enrolled1,282Registered outcomes5Posted comparisons9ConditionsType 2 DiabetesArmsdapagliflozin, Metformin XR, Placebo matching with Dapagliflozin, Placebo matching with Saxagliptin, Saxagliptin
Open the trial in the graph
NCT02946632 phase3unknown statusnot on this mapstarted 2016, after this paper: background citation

Effectiveness and Tolerability of Novel, Initial Triple Combination Therapy With Xigduo (Dapagliflozin Plus Metformin) and Saxagliptin vs. Conventional Stepwise add-on Therapy in Drug-naïve Patients With Type 2 Diabetes

TypeinterventionalSponsorKorea University Anam HospitalRan2016 to 2019Enrolled104ConditionsDiabetes Mellitus, Type IIArmstriple combination therapy, Stepwise add-on therapy
3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 21 syntheses or guidelines pooled it, 285 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Julio RosenstockDallas Diabetes and Endocrine Center, Dallas, TX juliorosenstock@dallasdiabetes.com.
Lars HansenBristol-Myers Squibb, Princeton, NJ.
Pamela ZeeBristol-Myers Squibb, Princeton, NJ.
Yan LiAstraZeneca, Wilmington, DE.
William CookAstraZeneca, Wilmington, DE.
Boaz HirshbergAstraZeneca, Wilmington, DE.
Nayyar IqbalBristol-Myers Squibb, Princeton, NJ.
AstraZeneca (United States) · USBristol-Myers Squibb (United States) · USDallas Diabetes Research Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study compared the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone in patients with type 2 diabetes poorly controlled with metformin. RESEARCH DESIGN AND

methodsThis was a double-blind trial in adults with HbA1c ≥8.0% and ≤12.0% (64-108 mmol/mol), randomized to saxagliptin (SAXA) (5 mg/day) plus dapagliflozin (DAPA) (10 mg/day; n = 179), or SAXA (5 mg/day) and placebo (n = 176), or DAPA (10 mg/day) and placebo (n = 179) on background metformin extended release (MET) ≥1,500 mg/day. Primary objective compared changes from baseline in HbA1c with SAXA+DAPA+MET versus SAXA+MET and DAPA+MET.

resultsPatients had a mean baseline HbA1c of 8.9% (74 mmol/mol), diabetes duration of 7.6 years, and a BMI of 32 kg/m(2). At week 24, the adjusted mean change from the baseline HbA1c was -1.5% (-16.1 mmol/mol) with SAXA+DAPA+MET versus -0.9% (-9.6 mmol/mol) with SAXA+MET (difference -0.59% [-6.4 mmol/mol], P < 0.0001) and -1.2% (-13.1 mmol/mol) with DAPA+MET (difference -0.27% [3.0 mmol/mol], P < 0.02). The proportion of patients achieving HbA1c <7% (53 mmol/mol) was 41% with SAXA+DAPA+MET versus 18% with SAXA+MET and 22% with DAPA+MET. Urinary and genital infections occurred in ≤1% of patients receiving SAXA+DAPA+MET. Hypoglycemia was infrequent, with no episodes of major hypoglycemia.

conclusionsIn this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin, greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin alone.

Indexed as

AdamantaneAdultAgedBenzhydryl CompoundsBlood GlucoseDiabetes Mellitus, Type 2DipeptidesDouble-Blind MethodDrug Therapy, CombinationFemaleGlucosidesHumansHypoglycemiaMaleMetforminMiddle AgedAdamantaneBenzhydryl CompoundsBlood GlucosedapagliflozinDipeptidesGlucosidesMetforminsaxagliptin

Identifiers

PMID25352655
OpenAlexW2161852973

What OpenQuestion 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 OpenQuestion graph.