Evidence map›Paper›PMID 26900641›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2016

Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study.

Vanita R Aroda, Sharon L Edelstein, Ronald B Goldberg, William C Knowler, Santica M Marcovina, Trevor J Orchard, George A Bray, David S Schade, Marinella G Temprosa, Neil H White and 2 more

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
251citing papers in PubMed, 10 pooled it
34.1field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

251 citing papers in PubMed, 10 syntheses or guidelines pooled it, 505 citations in OpenAlex.

  1. Pooled it
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  5. Do oral antidiabetic medications alter the risk of Parkinson's disease? An updated systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023 · on this map
    Pooled it
  6. 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
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  17. [Treatment of type 2 diabetes mellitus].Innere Medizin (Heidelberg, Germany) · 2026
    Article
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191 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 10 institutions in 1 country.

Vanita R ArodaMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Sharon L EdelsteinMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Ronald B GoldbergMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
William C KnowlerMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Santica M MarcovinaMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Trevor J OrchardMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
George A BrayMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
David S SchadeMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Marinella G TemprosaMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Neil H WhiteMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Jill P CrandallMedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782; George Washington University (S.L.E., M.G.T.), Rockville, MD 20852; University of Miami (R.B.G.), Miami, Florida 33146; National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014; University of Washington (S.M.M.), Seattle, Washington 98185; University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260; Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808; University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131; Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110; and Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461.
Diabetes Prevention Program Research Group
George Washington University · USAlbert Einstein College of Medicine · USMedStar Health · USNational Institute of Diabetes and Digestive and Kidney Diseases · USPennington Biomedical Research Center · USUniversity of Miami · USUniversity of New Mexico · USUniversity of Pittsburgh · USUniversity of Washington · USWashington University in St. Louis · US

Funding

PRIMARY PREVENTION TRIAL--DATA COORDINATING CENTERU01DK048489 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI JABLONSKI, KATHLEEN ANN, TEMPROSA, MARINELLA · 1994 to 2021
$84.8M
Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
Maternal Morbidity and Mortality: Risk Factors, Early Detection and Personalized InterventionUL1TR001409 · NCATS · GEORGETOWN UNIVERSITY · PI GONDRE-LEWIS, MARJORIE C, MELLMAN, THOMAS A · 2015 to 2024
$37.8M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Post-DDP Follow-up StudyU01DK048413 · NIDDK · UNIVERSITY OF WASHINGTON · PI KAHN, STEVEN EMANUEL · 1994 to 2021
$13.7M
PRIMARY PREVENTION TRIAL (DPT-2)U01DK048397 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI NATHAN, DAVID M · 1994 to 2021
$12.0M
NIDDM PRIMARY PREVENTION TRIAL (DPT 2)U01DK048404 · NIDDK · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI LAFERRERE, BLANDINE B · 1994 to 2021
$11.6M
NIDDM PRIMARY PREVENTION TRIALU01DK048412 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VENDITTI, ELIZABETH MARY · 1994 to 2021
$11.4M
PRIMARY PREVENTION TRIALU01DK048387 · NIDDK · MEDSTAR RESEARCH INSTITUTE · PI MAGEE, MICHELLE FISCHMANN · 1994 to 2022
$11.1M
TITLE OMITTEDU01DK048349 · NIDDK · YESHIVA UNIVERSITY · PI CRANDALL, JILL P · 1994 to 2021
$11.0M
PRIMARY PREVENTION TRIALU01DK048443 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WATSON, KAROL E · 1994 to 2021
$10.2M
Post-DPP Follow-up StudyU01DK048375 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI DABELEA, DANA · 1994 to 2022
$10.0M
NCATS NIH HHS UL1 TR001409NIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK020541NIDDK NIH HHS R01 DK078907NIDDK NIH HHS U01 DK048349NIDDK NIH HHS U01 DK048375NIDDK NIH HHS U01 DK048377NIDDK NIH HHS U01 DK048380NIDDK NIH HHS U01 DK048381NIDDK NIH HHS U01 DK048387NIDDK NIH HHS U01 DK048397NIDDK NIH HHS U01 DK048400NIDDK NIH HHS U01 DK048404NIDDK NIH HHS U01 DK048406NIDDK NIH HHS U01 DK048407NIDDK NIH HHS U01 DK048411NIDDK NIH HHS U01 DK048412NIDDK NIH HHS U01 DK048413NIDDK NIH HHS U01 DK048434NIDDK NIH HHS U01 DK048437NIDDK NIH HHS U01 DK048443NIDDK NIH HHS U01 DK048468NIDDK NIH HHS U01 DK048485NIDDK NIH HHS U01 DK048489NIDDK NIH HHS U01 DK048514
6 · The paper itself

Abstract

contextVitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use.

objectiveTo assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS).

designSecondary analysis from the DPP/DPPOS. Participants were assigned to the placebo group (PLA) (n = 1082) or the metformin group (MET) (n = 1073) for 3.2 years; subjects in the metformin group received open-label metformin for an additional 9 years.

settingTwenty-seven study centers in the United States. PATIENTS: DPP eligibility criteria were: elevated fasting glucose, impaired glucose tolerance, and overweight/obesity. The analytic population comprised participants with available stored samples. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764) in PLA and MET, respectively.

interventionMetformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS).

main outcome measuresB12 deficiency, anemia, and peripheral neuropathy.

resultsLow B12 (≤ 203 pg/mL) occurred more often in MET than PLA at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (≤ 298 pg/mL) was more common in MET at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Years of metformin use were associated with increased risk of B12 deficiency (odds ratio, B12 deficiency/year metformin use, 1.13; 95% confidence interval, 1.06–1.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels.

conclusionsLong-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.

Indexed as

AdultAgedAnemiaDiabetes Mellitus, Type 2FemaleHomocysteineHumansHypoglycemic AgentsMaleMetforminMiddle AgedVitamin B 12Vitamin B 12 DeficiencyHomocysteineHypoglycemic AgentsMetforminVitamin B 12

Identifiers

PMID26900641
PMCPMC4880159
OpenAlexW2275928777

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Texttitle and abstract
Read underepoch 390

Registered trials

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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.