Anastasia-Vasiliki Madenidou, MD, MSc; Paschalis Paschos, MD, MSc; Thomas Karagiannis, MD, MSc; Anastasia Katsoula, MD, MSc; Eleni Athanasiadou, MSc; Konstantinos Kitsios, MD, PhD; Eleni Bekiari, MD, PhD, MSc; David R. Matthews, MD, DPhil; Apostolos Tsapas, MD, PhD, MSc
Acknowledgment: The authors thank Associate Professor Bettina Haidich, Dr. Panagiotis Andreadis, and Dr. Ioannis Avgerinos for their contributions to this study. Dr. Tsapas received support from the Tseu Medical Institute at Harris Manchester College, University of Oxford, Oxford, United Kingdom.
Disclosures: Dr. Kitsios reports personal fees from Novo Nordisk, Sanofi, Medtronic, and Galenica outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0443.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Registered at PROSPERO (CRD42016037055). Statistical code: Not available. Data set: Available from Dr. Madenidou (e-mail, firstname.lastname@example.org).
Corresponding Author: Apostolos Tsapas, MD, PhD, MSc, Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Konstantinupoleos 49, 54642 Thessaloniki, Greece; e-mail, email@example.com.
Current Author Addresses: Drs. Madenidou, Paschos, Karagiannis, Katsoula, Kitsios, Bekiari, and Tsapas and Ms. Athanasiadou: Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Konstantinupoleos 49, 54642, Thessaloniki, Greece.
Dr. Matthews: Harris Manchester College, University of Oxford, Mansfield Road, Oxford OX1 3TD, United Kingdom.
Author Contributions: Conception and design: A.V. Madenidou, P. Paschos, A. Tsapas.
Analysis and interpretation of the data: A.V. Madenidou, P. Paschos, T. Karagiannis, K. Kitsios, E. Bekiari, D.R. Matthews, A. Tsapas.
Drafting of the article: A.V. Madenidou, T. Karagiannis, A. Katsoula, K. Kitsios, E. Bekiari, A. Tsapas.
Critical revision of the article for important intellectual content: A.V. Madenidou, P. Paschos, T. Karagiannis, D.R. Matthews, A. Tsapas.
Final approval of the article: A.V. Madenidou, P. Paschos, T. Karagiannis, A. Katsoula, E. Athanasiadou, K. Kitsios, E. Bekiari, D.R. Matthews, A. Tsapas.
Statistical expertise: A.V. Madenidou, P. Paschos, E. Bekiari, A. Tsapas.
Administrative, technical, or logistic support: E. Athanasiadou.
Collection and assembly of data: A.V. Madenidou, A. Katsoula, E. Athanasiadou.
Basal insulin analogues aim for protracted glycemic control with minimal adverse effects.
To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM).
Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books.
Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues.
Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence.
Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300.
Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency.
Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300).
None. (PROSPERO: CRD42016037055)
Madenidou A, Paschos P, Karagiannis T, et al. Comparative Benefits and Harms of Basal Insulin Analogues for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2018;169:165–174. [Epub ahead of print 10 July 2018]. doi: https://doi.org/10.7326/M18-0443
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Published: Ann Intern Med. 2018;169(3):165-174.
Published at www.annals.org on 10 July 2018
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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