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Quantification of Insulin Adherence in Adults with Insulin-treated Type 2
Diabetes: A Protocol for a Systematic Review
Jannie Toft Damsgaard Nørlev1, Morten Hasselstrøm Jensen1,2, Ole Hejlesen1, Tinna Björk Aradóttir3, Nicholas Ciccone3,
Stine Hangaard1,2
1Aalborg University, Health Science and Technology, Faculty of Medicine, Denmark jadano@hst.aau.dk
2Steno Diabetes Center North Denmark. Aalborg, Denmark
3Novo Nordisk A/S, Bagsværd, Denmark
Abstract
A systematic review will be conducted to update the evidence base and provide an overview of insulin adherence
quantification in adults with insulin-treated type 2 diabetes, i.e., the methods used to assess insulin adherence and
the cut-off points that constitute adequate insulin adherence.
Keywords
Type 2 Diabetes, Insulin Adherence, Quantification, Systematic Review
1 INTRODUCTION
The progressive nature of type 2 diabetes (T2D)
necessitates insulin therapy for most people to achieve
glycaemic control [1]. Although the full benefit of insulin
therapy will be accomplished only if the person with T2D
complies with the prescribed insulin regimen reasonably
closely [2], nonadherence to insulin therapy is common in
adults with T2D [3].
While nonadherence is recognized as a key contributor to
poor outcomes, many clinicians feel unable to address
nonadherence [2]. A study by MacEwan et al. demonstrated
that assessment of adherence rates is generally not better
than a random guess (53 vs. 50%) [4].
Precise measure or assessment of insulin adherence is
acknowledged as an important prerequisite to improving
insulin nonadherence [3] and interpreting the effects of an
intervention [5]. Results and clinical outcomes from an
intervention cannot be interpreted realistically without
information regarding correct adherence, i.e., if therapy
fails to achieve the desired outcome, there is a risk that the
clinician or researcher assume that a drug failure has
occurred if adherence is assessed incorrectly and
nonadherence, therefore, is not discovered [5]. Yet, there is
no gold-standard method to assess insulin adherence and no
cut-off point or consensual standard for what constitutes
adequate insulin adherence [2].
In recent years, advances in technology have brought
improvements in the field of diabetes. The spectrum of new
technologies spans smartphone apps, smart pens, and
insulin pumps [6]. Access to these new technologies may
have had an impact on how insulin adherence is assessed.
Despite this, no systematic review within the area has been
published since 2016 [7].
This systematic review aims to update the evidence base by
including literature published from 2012 to the time of the
review and provide an overview of the methods used to
assess insulin adherence and the cut-off points that
constitute adequate insulin adherence in adults with insulin-
treated T2D.
2 METHODS
A systematic review will be conducted and reported
according to the PRISMA 2020 checklist [8]. The
systematic review protocol was submitted for registration
with PROSPERO on May 20, 2022 and has not yet received
a registration number. The protocol will form the basis of
the review. The review process is illustrated in Figure 1.
Figure 1. The review process.
The 18th Scandinavian Conference on Health informatics, Tromsø, Norway, August 22-24, 2022. 218
To qualify the systematic search preliminary searches will
be performed to obtain an overview of published literature
and to identify relevant index terms, search terms, and
keywords. A systematic search will be performed in
PubMed, Embase, Cinahl, and PsycINFO. The search will
include three blocks: type 2 diabetes, insulin, and
adherence. Synonyms, near-synonyms, acronyms, index
terms, and spellings for each keyword will be identified.
Different search functions such as Boolean operators,
truncation, thesaurus, phrase searching, and text word (title,
abstract, keyword) will be applied to focus and structure the
search. Studies published from 2012 to the time of the
review and describe a method to assess insulin adherence
and include details on the cut-off point will be considered.
Primary full-text studies in English, Danish, Norwegian, or
Swedish will be screened for inclusion, except for study
protocols and animal research. Reference lists will be hand-
searched and citation searching will be conducted to
identify additional relevant studies within the field.
Data extraction will include details of the methods and cut-
off points used to assess insulin adherence, insulin regimen,
the population, and study design. The risk of bias will be
assessed for each of the included studies using critical
appraisal tools from the Joanna Briggs Institute (JBI) [9].
The results of the systematic search, screening, and risk of
bias assessment will be reported in full in the systematic
review. By the PRISMA guidelines, the screening process
will be presented in a PRISMA 2020 flow diagram [8]. A
narrative synthesis will be provided with the information
presented in text and tables. The identified methods to
assess insulin adherence will guide the organization and
description of the results. Cut-off points from each study
will be listed.
The systematic search will be performed by one reviewer
and facilitated by a research librarian with expertise and
experience in medical science and diabetes. Title and
abstract screening will be done by one reviewer, while two
independent reviewers will screen full-text articles. Data
extraction and analysis will be performed by one reviewer.
In the event of questions or doubts, the review co-authors
will be consulted, and an agreement will be reached by
discussion.
3 RESULTS
The results will update the evidence base by providing an
overview of the reported methods to assess insulin
adherence and the cut-off points used to define adequate
adherence. Potential novel methods or technologies to
assess insulin adherence will be included and the results
will provide insight into potential gaps within the field. The
results are expected to be published by the end of 2022.
4 DISCUSSION AND CONCLUSIONS
This systematic review will clarify methods used to assess
insulin adherence and the cut-off points that constitute
adequate insulin adherence in adults with T2D. Potentially,
the results can be used to guide clinicians and researchers
when selecting a method to assess insulin adherence in
adults with T2D. The systematic review may also inform of
new methods or technologies used to assess insulin
adherence if such has been implemented. Hence, the results
could potentially pioneer the implementation of future
technologies or methods for the assessment of insulin
adherence in adults with T2D.
5 REFERENCES
[1] Mahler, RJ., Adler, ML. ”Type 2 Diabetes Mellitus:
Update on Diagnosis, Pathophysiology, and
Treatment” in The Journal of Clinical Endocrinology
& Metabolism Vol. 84, Issue 4, pp. 1165-1171. 1999.
[2] Osterberg, L., Blaschke, T. “Adherence to
Medication” in N Engl J Med Vol. 353, Issue 5, pp.
487-497. 2005.
[3] Cramer, JA. “A Systematic Review of Adherence
With Medications for Diabetes” in Diabetes Care
Vol. 27, Issue 5, pp. 1218-1224. 2004.
[4] MacEwan, JP., Silverstein, AR., Shafrin, J.,
Lakdawalla, DN., Hatch, A., Forma, FM. “Medication
Adherence Patterns Among Patients with Multiple
Serious Mental and Physical Illnesses” in Adv Ther.
Vol. 35, Issue 5, pp. 671-685. 2018.
[5] Farmer, KC. “Methods for Measuring and Monitoring
Medication Regimen Adherence in Clinical Trials and
Clinical Practice” in Clinical Therapeutics Vol. 21,
Issue 6, pp. 1074-1090. 1999.
[6] Adolfsson, P., Hartvig, N., Kaas, A., Møller, J.,
Hellman, J. “Increased time in range and fewer missed
Bolus Injections after introduction of a smart
connected insulin pen” in Diabetes Technology and
Therapeutics Vol. 22, Issue 10, pp. 709-718. 2020.
[7] Stolpe, S., Kroes, MA., Webb, N., Wisniewski, T. “A
Systematic Review of Insulin Adherence Measures in
Patients with Diabetes” in JMCP Vol. 22, Issue 11, pp
1224-1246. 2016.
[8] Page, MJ., McKenzie, JE., Bossuyt, PM., et al. ”The
PRISMA 2020 statement: An updated guideline for
reporting systematic reviews” in BJM Vol. 372, Issue
71. 2021.
[9] Aromataris, E., Munn, Z., “JBI Manual for Evidence
Synthesis” in JBI, pp. 217-270. 2020.
219 The 18th Scandinavian Conference on Health informatics, Tromsø, Norway, August 22-24, 2022.
