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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Public Health Rev.</journal-id>
<journal-title-group>
<journal-title>Public Health Reviews</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Public Health Rev.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2107-6952</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">1608655</article-id>
<article-id pub-id-type="doi">10.3389/phrs.2026.1608655</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>A realist review to understand the complexity of effective management of type 2 diabetes and hypertension</article-title>
<alt-title alt-title-type="left-running-head">Ehteshami et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/phrs.2026.1608655">10.3389/phrs.2026.1608655</ext-link>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Ehteshami</surname>
<given-names>Fatemeh</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3047588"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Verjans</surname>
<given-names>Anna</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3414347"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cassidy</surname>
<given-names>Rachel</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3502388"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tediosi</surname>
<given-names>Fabrizio</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1054376"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fink</surname>
<given-names>G&#xfc;nther</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1056464"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Cobos Mu&#xf1;oz</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1550424"/>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
<institution>Swiss Tropical and Public Health Institute (Swiss TPH)</institution>, <city>Allschwil</city>, <country country="CH">Switzerland</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>University of Basel</institution>, <city>Basel</city>, <country country="CH">Switzerland</country>
</aff>
<aff id="aff3">
<label>3</label>
<institution>KPM Center for Public Management, University of Bern</institution>, <city>Bern</city>, <country country="CH">Switzerland</country>
</aff>
<aff id="aff4">
<label>4</label>
<institution>Swiss Institute for Translational and Entrepreneurial Medicine</institution>, <city>Bern</city>, <country country="CH">Switzerland</country>
</aff>
<aff id="aff5">
<label>5</label>
<institution>University of Milan</institution>, <city>Milan</city>, <country country="CH">Switzerland</country>
</aff>
<author-notes>
<corresp id="c001">
<label>&#x2a;</label>Correspondence: Fatemeh Ehteshami, <email xlink:href="mailto:fatemeh.ehteshami@swisstph.ch">fatemeh.ehteshami@swisstph.ch</email>; Daniel Cobos Mu&#xf1;oz, <email xlink:href="mailto:daniel.cobos@swisstph.ch">daniel.cobos@swisstph.ch</email>
</corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-06-01">
<day>01</day>
<month>06</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>47</volume>
<elocation-id>1608655</elocation-id>
<history>
<date date-type="received">
<day>01</day>
<month>05</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>07</day>
<month>03</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>05</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2026 Ehteshami, Verjans, Cassidy, Tediosi, Fink and Cobos Mu&#xf1;oz.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Ehteshami, Verjans, Cassidy, Tediosi, Fink and Cobos Mu&#xf1;oz</copyright-holder>
<license>
<ali:license_ref start_date="2026-06-01">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. PHR is edited by the Swiss School of Public Health (SSPH&#x2b;) in a partnership with the Association of Schools of Public Health of the European Region (ASPHER)&#x2b;</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Objectives</title>
<p>We aimed to disentangle the mechanisms that govern the effective management of diabetes and/or hypertension in various contexts in low- and middle-income countries.</p>
</sec>
<sec>
<title>Methods</title>
<p>We conducted a realist review guided by the Realist and MEta-narrative Evidence Syntheses Evolving Standards. We systematically searched electronic databases to examine in what contexts, how, and for whom programs targeting diabetes and/or hypertension care work through context-mechanism-outcome (CMO) configurations and then revised an initial program theory to a refined program theory.</p>
</sec>
<sec>
<title>Results</title>
<p>We identified four CMO configurations. (1) Cross-sectoral partnerships activate the mechanisms of resource pooling and mobilization, improving healthcare services coverage and fostering sustainable local buy-in (2) Integration of disease-specific programs facilitates coordinated care, resulting in treatment adherence (3) Digitalized infrastructure and literacy enable the mechanisms of mHealth and eHealth implementation and clinical decentralization, improving access, coordination, and treatment adherence (4) Patient-centered care triggers the mechanisms of patient-provider communication and personalized care, leading to patient engagement and health education.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>This review provides insights into the relevance of contexts and their associated mechanisms for operationalizing successful models of care for diabetes and/or hypertension that enhance health outcomes.</p>
</sec>
</abstract>
<kwd-group>
<kwd>hypertension (HTN)</kwd>
<kwd>low and middle income countries (LMICs)</kwd>
<kwd>realist review</kwd>
<kwd>systems thinking</kwd>
<kwd>type 2 diabetes mellitus</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. FE is supported by the Swiss Government Excellence Scholarships for Foreign Scholars (2021.0883).</funding-statement>
</funding-group>
<counts>
<fig-count count="2"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="93"/>
<page-count count="13"/>
</counts>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>The global prevalence of Diabetes Mellitus (DM) and Hypertension (HTN) has increased over the past few decades [<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>], yet effective management of these conditions remains suboptimal in many settings, particularly in low- and middle-income countries [<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>]. A cross-sectional study analyzing the results of nationally representative surveys determined that the total unmet need for DM care in 28 LMICs is estimated to be 77%, which is the sum of cases that are undetected, detected but undiagnosed, diagnosed but untreated, and treated but not controlled. The unmet need and low rate of control (22.8%) indicate a significant gap in DM care in LMICs [<xref ref-type="bibr" rid="B5">5</xref>]. A further study of the care cascade for HTN in low-income settings found only 16% of hypertensive patients had achieved control, with 48% of people with HTN being aware of their condition and 35% receiving treatment [<xref ref-type="bibr" rid="B6">6</xref>]. Poor control of DM and HTN accelerates their progression to complicated conditions such as cardiovascular disease [<xref ref-type="bibr" rid="B7">7</xref>&#x2013;<xref ref-type="bibr" rid="B9">9</xref>]. Therefore, effective management of patients living with these conditions is crucial.</p>
<p>The required continuous and coordinated care and the presence of comorbidities with DM and HTN further complicate effective management. Common comorbidities of diabetic patients include peripheral vascular disease, end-stage renal disease, blindness, and amputations [<xref ref-type="bibr" rid="B9">9</xref>]. HTN is also the primary risk factor contributing to the development of atherosclerotic vascular diseases such as cardiac, cerebrovascular, and renal conditions [<xref ref-type="bibr" rid="B10">10</xref>]. There are other comorbidities with DM and/or HTN, such as depression [<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>], obesity [<xref ref-type="bibr" rid="B13">13</xref>], DM and tuberculosis [<xref ref-type="bibr" rid="B14">14</xref>], and HIV/AIDS [<xref ref-type="bibr" rid="B15">15</xref>].</p>
<p>Due to the complications that arise from ineffective DM and HTN management, it is critical that we identify and understand the complex and multifaceted pathways for effective DM and HTN care. Previous reviews identified several key factors of an effective model of care that contribute to the management of DM and/or HTN in LMICs, such as quality communication among providers and patients, the availability of essential medicines, trained health professionals at decentralized levels, coordination between providers, standardization of clinical guidelines, community and peer engagement, and the integration of technologies into disease management [<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B17">17</xref>]. Despite these insights, there remains a need for research that explores the causal linkages among these factors and examines the underlying contexts and mechanisms that influence the management of these conditions.</p>
<p>A realist review evidentiary approach was appropriate for this study as it is used to unravel how a program works (or does not work) by addressing what works, for whom, and in what circumstances through Context, Mechanism, Outcome (CMO) configurations [<xref ref-type="bibr" rid="B18">18</xref>]. We conducted a realist review to understand how, in what contexts, and for whom multicomponent programs targeting DM and/or HTN management are effective - in other words, to identify mechanisms of DM and/or HTN management by which these programs lead to specific health outcomes across various contexts.</p>
</sec>
<sec sec-type="methods" id="s2">
<title>Methods</title>
<sec id="s2-1">
<title>Study design</title>
<p>This realist review followed the Realist and MEta-narrative Evidence Syntheses Evolving Standards (RAMESES), guided by a checklist (<xref ref-type="sec" rid="s9">Supplementary Data Sheet 1</xref>) [<xref ref-type="bibr" rid="B19">19</xref>]. The study protocol was published in PROSPERO (registration code: CRD42023445454), with further rationale and the methodological approach defined in a peer-reviewed protocol [<xref ref-type="bibr" rid="B20">20</xref>]. This review used existing published literature; therefore, ethical approval was not required. The study phases were conducted according to Pawson et al.&#x2019;s methodology for a realist review [<xref ref-type="bibr" rid="B18">18</xref>]. A realist review is characterized by several key components, namely: an initial program theory, context, mechanism, outcome (CMO) configuration, and a refined program theory [<xref ref-type="bibr" rid="B21">21</xref>] <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Components of realist terms in the review (A realist review to understand the complexity of effective management of type 2 diabetes and hypertension, 2013&#x2013;2023) (low- and middle-income countries).</p>
</caption>
<table>
<tbody valign="top">
<tr>
<td align="center">Initial program theory</td>
<td align="left">A combination of factors that conceptualize how DM and/or HTN management in LMICs work. A CLD based on a preliminary review of evidence serves as an initial program theory in this review</td>
</tr>
<tr>
<td align="center">Context</td>
<td align="left">Any state that affects how a mechanism is implemented. It might facilitate, activate, or deactivate a mechanism</td>
</tr>
<tr>
<td align="center">Mechanism</td>
<td align="left">A process triggered and generated in specific contexts that leads to health outcomes</td>
</tr>
<tr>
<td align="center">Outcome</td>
<td align="left">A result of the interaction of mechanisms under a specific context</td>
</tr>
<tr>
<td align="center">Refined program theory</td>
<td align="left">Identified CMO configurations update and refine the initial program theory to a refined program theory</td>
</tr>
</tbody>
</table>
</table-wrap>
<sec id="s2-1-1">
<title>First phase: conceptualization of the initial program theory to address the complexity of DM and HTN management in LMICs using a CLD</title>
<p>W adopted a systems thinking approach, specifically the use of a causal loop diagram (CLD) to unpack the complexity of DM and/or HTN management and understand which underlying factors influence the (in)effective management of these conditions. Systems thinking is a way to understand complex, dynamic, and interconnected systems by emphasizing relationships rather than isolated components [<xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B23">23</xref>]. Through a range of tools and techniques, systems thinking approaches seek to identify interconnections among system elements and processes [<xref ref-type="bibr" rid="B24">24</xref>]. CLDs are one systems thinking tools that offer valuable insights to key actors by illustrating the interactions between system components and the causal linkages involved in addressing a problem [<xref ref-type="bibr" rid="B25">25</xref>].</p>
<p>In this phase, we developed a CLD as a problem-driven tool and representation of the initial program theory. To this end, we conducted a preliminary search and reviewed articles, including qualitative studies, mixed-method studies, and reviews. We particularly delved into qualitative case studies in LMICs, which offered opportunities to delineate the causal pathways and inform the CLD development according to the perceptions of healthcare providers and patients with DM and/or HTN. We extracted the healthcare provider-related factors, such as availability, accessibility, and knowledge of healthcare workers, and patient-related factors, such as awareness and knowledge, treatment adherence, care-seeking behavior, and financial constraints, and then mapped them through a CLD. This phase of work is completed and published elsewhere [<xref ref-type="bibr" rid="B20">20</xref>].</p>
</sec>
<sec id="s2-1-2">
<title>Second phase: search, selection, appraisal, and extraction of evidence regarding programs for DM and/or HTN management in LMICs</title>
<p>In this phase, we developed inclusion/exclusion criteria and search strategies and conducted systematic literature searches. We then assessed the quality of the included eligible studies and extracted the data to identify CMO configurations within programs targeting healthcare services for the management of DM and/or HTN.</p>
<sec id="s2-1-2-1">
<title>Eligibility criteria</title>
<p>The list of inclusion and exclusion criteria is shown in <xref ref-type="table" rid="T2">Table 2</xref>. We included articles in English published between 2013 and 2023 describing healthcare services related to the management of Type 2 Diabetes Mellitus (T2DM) and/or HTN in LMICs. The management of T2DM and HTN was defined as approaches that enable achieving and maintaining glycemic control and blood pressure levels, preventing or delaying complications, and enhancing quality of life [<xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>]. The list of countries defined as LMICs followed the World Bank classification of <italic>per capita</italic> gross national income in 2021 [<xref ref-type="bibr" rid="B28">28</xref>]. Studies describing the management of Type 1 Diabetes Mellitus (T1DM), gestational, monogenetic, or secondary DM were excluded as different approaches should be adopted for various types of DM [<xref ref-type="bibr" rid="B29">29</xref>]. All studies had to meet all inclusion criteria.</p>
<table-wrap id="T2" position="float">
<label>TABLE 2</label>
<caption>
<p>Eligibility criteria for literature review (A realist review to understand the complexity of effective management of type 2 diabetes and hypertension, 2013&#x2013;2023) (low- and middle-income countries).</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Criteria</th>
<th align="left">Inclusion</th>
<th align="left">Exclusion</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="3" align="left">Type of study</td>
<td align="left">Studies that incorporated at least two elements of the WHO building blocks other than healthcare services delivery [<xref ref-type="bibr" rid="B30">30</xref>]</td>
<td rowspan="3" align="left">Studies without the description of programs and mechanisms, and without analysis of control of DM and/or HTN</td>
</tr>
<tr>
<td align="left">All types of studies that described the implementation of programs and healthcare services related to the management of T2DM and/or HTN</td>
</tr>
<tr>
<td align="left">Studies that analyzed the outcomes related to clinical control of DM and/or HTN</td>
</tr>
<tr>
<td align="left">Countries</td>
<td align="left">LMICs</td>
<td align="left">HICs</td>
</tr>
<tr>
<td align="left">Setting</td>
<td align="left">Primary healthcare facilities</td>
<td align="left">Other settings</td>
</tr>
<tr>
<td align="left">Language</td>
<td align="left">English</td>
<td align="left">Other languages</td>
</tr>
<tr>
<td align="left">Publication year</td>
<td align="left">2013&#x2013;2023</td>
<td align="left">Other years</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s2-1-2-2">
<title>Search strategy, study selection, and data extraction</title>
<p>We conducted a literature search in four electronic databases, namely CENTRAL, Web of Science, PubMed, Embase, and supplemented these with additional records from a manual search and reference lists of reviewed publications. We developed the search strategy using a combination of medical subject headings (MeSH) and free text, including terms related to &#x201c;healthcare services&#x201d;, &#x201c;intervention&#x201d; &#x201c;program&#x201d;, &#x201c;care model&#x201d;, &#x201c;type 2 diabetes&#x201d;, &#x201c;hypertension&#x201d;, and their synonyms and variant terms as shown in <xref ref-type="sec" rid="s9">Supplementary Data Sheet 2</xref>.</p>
<p>The screening process for the review is shown in detail in <xref ref-type="fig" rid="F1">Figure 1</xref>. We imported all evidence into EndNote and Covidence as a tool for screening titles/abstracts and full texts. Two independent authors (FE and AV) screened full texts to assess eligibility. We recorded reasons for exclusion and resolved any disagreements through discussion to reach a consensus. In case they could not reach a consensus, the third author DC reviewed the study. We extracted key characteristics of the eligible studies, including study design, year of publication, setting, key contexts, mechanisms, and outcomes, which are summarized in <xref ref-type="sec" rid="s9">Supplementary Data Sheet 3</xref>.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Overview of study screening and inclusion (A realist review to understand the complexity of effective management of type 2 diabetes and hypertension, 2013&#x2013;2023) (low- and middle-income countries).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="phrs-47-1608655-g001.tif">
<alt-text content-type="machine-generated">PRISMA flow diagram illustrating study selection for a systematic review. Identification phase: 4,245 records from databases and 480 from manual searching. After removing 699 duplicates, 4,026 abstracts screened, with 3,864 records excluded. 162 articles screened for full text, 130 excluded for reasons such as ineligible population (9), context (18), intervention (55), study design (25), and outcomes (23). Final review included 32 studies.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s2-1-2-3">
<title>Assessment of study quality and publication bias</title>
<p>We assessed study quality and risk of bias with the Mixed Methods Appraisal Tool (MMAT) version 2018 [<xref ref-type="bibr" rid="B31">31</xref>]. Two reviewers (FE and AV) were involved in the quality assessment, and the third author DC was involved in solving any disagreements. The quality criteria of the MMAT tool were assessed by responding &#x201c;Yes&#x201d;, &#x201c;No&#x201d;, or &#x201c;Can&#x2019;t tell&#x201d; referring to whether the study did or did not meet each criterion. The first two criteria are independent of the study design, whereas the remaining five are defined according to the type of study, as shown in <xref ref-type="sec" rid="s9">Supplementary Data Sheet 4</xref>.</p>
</sec>
</sec>
<sec id="s2-1-3">
<title>Third phase: analysis of data, development of CMO configurations, and program theory refinement</title>
<p>The eligible studies were scrutinized to determine the CMO configurations for the management of DM and/or HTN. In a realist approach, data are not only limited to results and measured outcomes of a study but also contain author descriptions and discussions that serve as a rich and valuable data source that makes clear and explicit whether and how a program works [<xref ref-type="bibr" rid="B32">32</xref>]. Accordingly, the full texts of the included studies were reviewed to become familiar with the various programs implemented across different countries. Next, the descriptions of the programs and author explanations within the included studies (such as the design and implementation pathways, the components involved, how they were delivered, and the target population) were highlighted. The relevant information was extracted and compiled into a spreadsheet in a Word document, including the title, year of the study publication, country, study design, description of the program and health outcomes, and clinical effectiveness of DM and HTN. We then identified prominent patterns of contexts, mechanisms, and outcomes through the iterative analysis process by the research team.</p>
<p>Furthermore, the CLD was updated and revised according to the identified CMO configurations. We presented the causal links of the CLD by arrows and polarities (&#x2b;/&#x2212;) that show the relationship between two variables in which an increase or decrease in one variable influences the other variable in a similar (&#x2b;) or opposite (&#x2212;) way. A series of causal links created two key loop behaviors, either a positive (reinforcing) or a negative (balancing) loop. A balancing loop is self-correcting, as the effects are dampened throughout the loop. A reinforcing loop is self-reinforcing, as the effects are amplified throughout the loop, which may result in a virtuous cycle (desirable effects) or a vicious cycle (negative effects) [<xref ref-type="bibr" rid="B33">33</xref>, <xref ref-type="bibr" rid="B34">34</xref>].</p>
</sec>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<p>The initial search yielded 4,725 articles. We excluded 3864 studies after a preliminary screening process, resulting in 162 articles that were eligible for full-text screening. A total of 32 studies met all the inclusion criteria (see <xref ref-type="fig" rid="F1">Figure 1</xref>). Key characteristics of the included studies are shown in <xref ref-type="table" rid="T3">Table 3</xref>. One study included six middle-income countries, along with two high-income countries [<xref ref-type="bibr" rid="B35">35</xref>]. The geographical distribution and the number of included studies in each country are shown in <xref ref-type="sec" rid="s9">Supplementary Data Sheet 5</xref>.</p>
<table-wrap id="T3" position="float">
<label>TABLE 3</label>
<caption>
<p>Key characteristics of the included studies (A realist review to understand the complexity of effective management of type 2 diabetes and hypertension, 2013&#x2013;2023) (low- and middle-income countries).</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Authors/References</th>
<th align="center">Region(s)</th>
<th align="center">Publication year</th>
<th align="center">condition under study</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="center">Lim et al. [<xref ref-type="bibr" rid="B35">35</xref>]</td>
<td align="center">8 Asia-Pacific countries (India, Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam)</td>
<td align="center">2021</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Boch et al. [<xref ref-type="bibr" rid="B36">36</xref>]</td>
<td align="center">Mongolia, Senegal, Brazil</td>
<td align="center">2022</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Ali et al. [<xref ref-type="bibr" rid="B37">37</xref>]</td>
<td align="center">India and Pakistan</td>
<td align="center">2016</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Jafar et al. [<xref ref-type="bibr" rid="B38">38</xref>]</td>
<td align="center">Bangladesh, Pakistan, and Sri Lanka</td>
<td align="center">2016</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Hickey et al. [<xref ref-type="bibr" rid="B39">39</xref>]</td>
<td align="center">Kenya and Uganda</td>
<td align="center">2021</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Lou Q et al. [<xref ref-type="bibr" rid="B40">40</xref>]</td>
<td align="center">China</td>
<td align="center">2020</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Zhu et al. [<xref ref-type="bibr" rid="B41">41</xref>]</td>
<td align="center">China</td>
<td align="center">2018</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Wang et al. [<xref ref-type="bibr" rid="B42">42</xref>]</td>
<td align="center">China</td>
<td align="center">2021</td>
<td align="center">HTN and/or DM and COPD</td>
</tr>
<tr>
<td align="center">Jia et al. [<xref ref-type="bibr" rid="B43">43</xref>]</td>
<td align="center">China</td>
<td align="center">2021</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Sun et al. [<xref ref-type="bibr" rid="B44">44</xref>]</td>
<td align="center">China</td>
<td align="center">2022</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Zhou et al. [<xref ref-type="bibr" rid="B45">45</xref>]</td>
<td align="center">China</td>
<td align="center">2022</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Ajay et al. [<xref ref-type="bibr" rid="B46">46</xref>]</td>
<td align="center">India</td>
<td align="center">2016</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Ali et al. [<xref ref-type="bibr" rid="B47">47</xref>]</td>
<td align="center">India</td>
<td align="center">2020</td>
<td align="center">DM and depression</td>
</tr>
<tr>
<td align="center">Prabhakaran et al. [<xref ref-type="bibr" rid="B48">48</xref>]</td>
<td align="center">India</td>
<td align="center">2019</td>
<td align="center">HTN and DM</td>
</tr>
<tr>
<td align="center">Ramli et al. [<xref ref-type="bibr" rid="B49">49</xref>]</td>
<td align="center">Malaysia</td>
<td align="center">2016</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Low et al. [<xref ref-type="bibr" rid="B50">50</xref>]</td>
<td align="center">Malaysia</td>
<td align="center">2013</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Paluyo et al. [<xref ref-type="bibr" rid="B51">51</xref>]</td>
<td align="center">Philippines</td>
<td align="center">2021</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Pilleron et al. [<xref ref-type="bibr" rid="B52">52</xref>]</td>
<td align="center">Philippines</td>
<td align="center">2014</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Khan et al. [<xref ref-type="bibr" rid="B53">53</xref>]</td>
<td align="center">Pakistan</td>
<td align="center">2018</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Xie et al. [<xref ref-type="bibr" rid="B54">54</xref>]</td>
<td align="center">Bangladesh</td>
<td align="center">2023</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Chan et al. [<xref ref-type="bibr" rid="B55">55</xref>]</td>
<td align="center">Kazakhstan</td>
<td align="center">2020</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Valdes Gonzalez et al. [<xref ref-type="bibr" rid="B56">56</xref>]</td>
<td align="center">Cuba</td>
<td align="center">2020</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Dethlefs et al. [<xref ref-type="bibr" rid="B57">57</xref>]</td>
<td align="center">Dominican Republic</td>
<td align="center">2019</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Adler et al. [<xref ref-type="bibr" rid="B58">58</xref>]</td>
<td align="center">Ghana</td>
<td align="center">2019</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Collins et al. [<xref ref-type="bibr" rid="B59">59</xref>]</td>
<td align="center">Tajikistan</td>
<td align="center">2019</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Kingue et al. [<xref ref-type="bibr" rid="B60">60</xref>]</td>
<td align="center">Cameroon</td>
<td align="center">2013</td>
<td align="center">HTN</td>
</tr>
<tr>
<td align="center">Zou et al. [<xref ref-type="bibr" rid="B61">61</xref>]</td>
<td align="center">Sierra Leone</td>
<td align="center">2020</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Morelli et al. [<xref ref-type="bibr" rid="B62">62</xref>]</td>
<td align="center">Argentina</td>
<td align="center">2023</td>
<td align="center">DM</td>
</tr>
<tr>
<td align="center">Doocy et al. [<xref ref-type="bibr" rid="B63">63</xref>]</td>
<td align="center">Lebanon</td>
<td align="center">2017</td>
<td align="center">DM and HTN</td>
</tr>
<tr>
<td align="center">Ameh et al. [<xref ref-type="bibr" rid="B64">64</xref>]</td>
<td align="center">South Africa</td>
<td align="center">2017</td>
<td align="center">HTN, HIV</td>
</tr>
<tr>
<td align="center">Patel et al. [<xref ref-type="bibr" rid="B65">65</xref>]</td>
<td align="center">Malawi</td>
<td align="center">2018</td>
<td align="center">HTN and HIV</td>
</tr>
<tr>
<td align="center">Birungi et al. [<xref ref-type="bibr" rid="B66">66</xref>]</td>
<td align="center">Tanzania and Uganda</td>
<td align="center">2021</td>
<td align="center">DM, HTN and HIV</td>
</tr>
</tbody>
</table>
</table-wrap>
<sec id="s3-1">
<title>Study quality</title>
<p>The MMAT results suggest that the included studies were generally of good quality (<xref ref-type="sec" rid="s9">Supplementary Data Sheet 4</xref>). No study was excluded due to poor quality. For all studies, the first two questions regarding the clarity of the research questions and the relevance of the collected data to answer the research questions were selected &#x201c;Yes&#x201d;. In addition, three studies were program reports and could not be appraised using MMAT [<xref ref-type="bibr" rid="B51">51</xref>, <xref ref-type="bibr" rid="B56">56</xref>, <xref ref-type="bibr" rid="B65">65</xref>].</p>
</sec>
<sec id="s3-2">
<title>Context, mechanism, outcome (CMO) configurations</title>
<p>The analysis of the included studies supported four CMO configurations to explain how contexts and mechanisms influence outcomes.</p>
<sec id="s3-2-1">
<title>CMO1: cross-sectoral partnerships (C) pool and mobilize resources for the provision of healthcare services related to DM and HTN (M), improving healthcare services coverage and fostering sustainable local buy-in practices (O)</title>
<p>We found twelve studies conducted within the context of cross-sectoral partnerships. This allowed the implementation of mechanisms related to mobilizing and pooling resources for healthcare services that facilitated improved healthcare coverage and local buy-in [<xref ref-type="bibr" rid="B36">36</xref>, <xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B51">51</xref>&#x2013;<xref ref-type="bibr" rid="B53">53</xref>, <xref ref-type="bibr" rid="B55">55</xref>&#x2013;<xref ref-type="bibr" rid="B59">59</xref>, <xref ref-type="bibr" rid="B61">61</xref>, <xref ref-type="bibr" rid="B65">65</xref>]. For example, a study in Ghana examined the Community-based Hypertension Improvement Project (comHIP), a public-private partnership (PPP) between the Ghana Health Service (GHS), FHI 360 (formerly Family Health International), and the Novartis Foundation. In the comHIP, FHI 360 and the Ministry of Health (MoH) conducted training for healthcare workers. The authors highlighted that comHIP&#x2019;s strength lies in the local systems, such as the use of existing GHS protocols and medications, making it more sustainable compared to programs that depend on outside funding and resources. The outcomes of the implementation of comHIP showed that 72% (95% CI: 67%&#x2013;77%) of participants had controlled blood pressure [<xref ref-type="bibr" rid="B58">58</xref>]. Another study evaluated the implementation of a program (CARDIO4Cities) in Ulaanbaatar in Mongolia, Dakar in Senegal, and S&#xe3;o Paulo in Brazil. The selected cities represent diverse urban contexts across three continents; therefore, the program was tailored to address local priorities. It was co-designed between the Novartis Foundation and local authorities and public-private partners from various sectors. Mobilizing and engagement of non-traditional health players broadened opportunities for community outreach and HTN detection and awareness. The program was delivered based on contextual variations in health systems in each country. In Brazil, free treatment was available to all individuals according to local policy, whereas in other cities, the partnership worked with local authorities to incorporate HTN medicines into essential drug lists. This initiative, by engaging multiple partners and mobilizing non-health players, ensured local buy-in. The findings showed the proportion of enrolled patients who achieved HTN control while taking medication roughly tripled in S&#xe3;o Paulo (from 12.3% to 31.2%) and Dakar (from 6.7% to 19.4%), and increased more than six-fold in Ulaanbaatar (from 3.1% to 19.7%) [<xref ref-type="bibr" rid="B36">36</xref>].</p>
</sec>
<sec id="s3-2-2">
<title>CMO2: integration of disease-specific programs for chronic conditions (C) enhances team-based coordinated care for multiple chronic comorbidities (M), improving treatment adherence (O)</title>
<p>Several studies indicated that integrating disease-specific programs for specific chronic conditions creates concurrent team-based coordinated care for multiple chronic comorbidities. The interactions of mechanisms within this context enhance treatment adherence [<xref ref-type="bibr" rid="B39">39</xref>, <xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B47">47</xref>, <xref ref-type="bibr" rid="B64">64</xref>, <xref ref-type="bibr" rid="B65">65</xref>].</p>
<p>A prospective cohort study in Tanzania and Uganda examined the retention in care and clinical outcomes of an integrated care model for HIV, DM, and HTN. Integration translated in this case to setting up a single clinic for the management of patients with HIV, DM, or HTN, or a combination of these. Patients shared waiting areas, reception, and pharmacy, and were seen by the same clinical staff. In addition, systems for patient follow-up, counselling, appointments, registration, and recording clinical notes were aligned to streamline disease management regardless of the condition. Healthcare staff also received training in all three conditions to ensure a common understanding. The study reported high retention rates across disease categories, including 82.5% in HIV, 85% in DM, and 78.8% in HTN, and 90.9% among those with multimorbidity. Although blood pressure and blood glucose improved over time in this study, a high percentage of participants with HTN and DM continued to have uncontrolled levels. The authors highlighted that the limited availability of adequate monitoring tests for DM, particularly HbA1c testing, posed a challenge during the study [<xref ref-type="bibr" rid="B66">66</xref>]. Three studies in rural South Africa [<xref ref-type="bibr" rid="B64">64</xref>], Kenya and Uganda [<xref ref-type="bibr" rid="B39">39</xref>], and Malawi [<xref ref-type="bibr" rid="B65">65</xref>], respectively, tested an integrated model of care for HIV/AIDS and HTN. For example, the integrated HIV and HTN model of care in Malawi utilized a referral network for individuals with complicated HTN and developed an HTN-specific module in the Malawi electronic medical record system. The results showed that 11% of the population were newly diagnosed with HTN, and 85% of those received treatment. 38% and 30% had controlled mild HTN and moderate HTN, respectively [<xref ref-type="bibr" rid="B65">65</xref>]. However, the results of a controlled interrupted time-series study in South Africa, which examined the clinical effectiveness of a model of care, Integrated Chronic Disease Management (ICDM), on participants with HIV, HTN, and DM, indicated a small effect in the control of blood pressure (1% higher likelihood of achieving blood pressure control). The authors outlined that the failure to achieve successful blood pressure control in this setting may be due to health system and individual-related factors [<xref ref-type="bibr" rid="B64">64</xref>].</p>
<p>Furthermore, a randomized clinical trial at four socioeconomically diverse clinics in India examined the potential of an integrated coordinated care program for patients with DM and depression. The intervention used team-based, patient-centered approaches to overcome barriers and facilitate patient, clinician, and system-level mechanisms. Care coordinators and consulting specialists, such as psychiatrists and diabetologists, enhanced standard care by supporting diabetes physicians. The results showed an improvement of depressive symptoms, a reduction of at least 0.5 percentage points in HbA1c, and a reduction of at least 5&#xa0;mm Hg in systolic blood pressure. The authors also highlighted the increased access, feasibility, and acceptability of implementing the integrated collaborative model of care across various DM care settings [<xref ref-type="bibr" rid="B47">47</xref>].</p>
</sec>
<sec id="s3-2-3">
<title>CMO3: digitalized infrastructure and literacy (C), facilitate mHealth and eHealth implementation and clinical decentralization of DM and/or HTN (M), improving access, coordination, and treatment adherence (O)</title>
<p>Digital development and advancement in technology literacy [<xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B60">60</xref>, <xref ref-type="bibr" rid="B62">62</xref>] serve as an enabling context, which facilitates the implementation of mHealth, eHealth, and clinical decentralization of healthcare services. These mechanisms improve access, treatment adherence, and support coordination both among healthcare workers and between healthcare workers and patients [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B48">48</xref>, <xref ref-type="bibr" rid="B50">50</xref>, <xref ref-type="bibr" rid="B51">51</xref>, <xref ref-type="bibr" rid="B54">54</xref>, <xref ref-type="bibr" rid="B60">60</xref>, <xref ref-type="bibr" rid="B62">62</xref>, <xref ref-type="bibr" rid="B63">63</xref>, <xref ref-type="bibr" rid="B65">65</xref>].</p>
<p>A study in rural settings of Cameroon reported that infrastructure for a telemedicine center, TELEMED-CAM, at one of the two largest general hospitals was established, and specialized physicians were trained to utilize the computer software for the remote monitoring of patients. Healthcare workers in remote centers were also allowed to communicate and collaborate with the telecare center for further guidance on their decision-making and to receive immediate feedback. The study highlighted that the broad availability of mobile phones and the internet in Africa has offered new and affordable means of communication, which facilitated telemedicine as a potential alternative for enhancing access to chronic disease care where human resources are limited. In this study, blood pressure control among patients improved. Among participants with stage III HTN and participants with stage I and II HTN at baseline, 50% and 65.2% in the intervention group achieved the target blood pressure at the final visit (P &#x3d; 0.20) [<xref ref-type="bibr" rid="B60">60</xref>]. Another study in Argentina evaluated an intervention combining a mobile app with a DM registry, a provider-focused clinical decision support system, and a patient-targeted text messaging intervention. The authors noted that mobile technology&#x2019;s penetration is a significant driver that influences the implementation of digital health interventions. This study showed a significant increase in the percentage of participants undergoing laboratory check-ups and receiving pharmacological treatment. The study also found a decreased rate of uncontrolled blood pressure from 47.2% to 30.8% [<xref ref-type="bibr" rid="B62">62</xref>]. Moreover, a study in Lebanon underscored the enhanced patient-provider interactions via the implementation of an mHealth app. The results revealed a higher percentage of lifestyle counseling, medication complications, and follow-up scheduling. Systolic and diastolic blood pressure measurements decreased by 8.4% following the mHealth phase compared with baseline (P &#x3d; 0.001). The authors also reported that the mHealth app has the potential to enhance adherence to guidelines in Lebanon [<xref ref-type="bibr" rid="B63">63</xref>].</p>
</sec>
<sec id="s3-2-4">
<title>CMO4: patient-centered care (C) leads to improved patient-provider communication and personalized care (M), increasing patient engagement and health education (O)</title>
<p>Some studies indicated that patient-centered care [<xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B49">49</xref>] enhances interpersonal communication between healthcare providers and patients, and personalized care, leading to improved patient engagement and health education [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B37">37</xref>, <xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B43">43</xref>&#x2013;<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B49">49</xref>, <xref ref-type="bibr" rid="B50">50</xref>].</p>
<p>In a study conducted in China, a nurse-led HTN management team adopting the Chronic Care Model incorporated home visits, telephone follow-ups, and assistance in improving patients&#x2019; self-management and health education. Patients also received a free annual health check. The results showed that the reductions in systolic blood pressure and diastolic blood pressure in the study group compared to the control group were &#x2212;14.37&#xa0;mmHg and &#x2212;7.43 mmHg, respectively and were significant (P &#x3d; 0.003 and P &#x3d; 0.002). Patients also had significantly greater improvement in self-care behaviors and a higher level of satisfaction [<xref ref-type="bibr" rid="B41">41</xref>]. Similarly, in another study conducted in China, the primary care physician provided health education and medication advice to a patient face-to-face or through text messages. Blood pressure control rates were 47.4% in the intervention group and 30.2% in the control group (P &#x3c;0 .001). The authors highlighted that the positive results on HTN management are potentially due to the various components being coordinated in a way that improved communication between patients and their primary care physicians, and that telemedicine provided an effective and new way for managing this condition [<xref ref-type="bibr" rid="B45">45</xref>].</p>
<p>Personalized care, as part of patient-centered care, allows for customizing patients&#x2019; treatment through health technologies, as outlined in two studies. For example, a study conducted in eight Asia-Pacific countries used technology-guided structured evaluation (JADE) to personalize reports to encourage patient empowerment and patient engagement. Nurses were trained to use the JADE technology. The use of information and communications technology and nurses to empower and engage patients reduced cardiometabolic risk factors, such as HbA1c, among patients with T2DM without affecting clinical event rates. The effects were stronger in LMICs [<xref ref-type="bibr" rid="B35">35</xref>]. Similarly, a study in India integrated nurse-led care coordination with a mobile phone-based clinical decision support system (mDSS), which was used to create a personalized patient management plan. The results showed 52% of newly detected cases of HTN and 30% of DM. The reductions in systolic blood pressure, diastolic blood pressure, and fasting plasma glucose observed equaled 14.6&#xa0;mm Hg (95% CI: 15.3, 13.8), 7.6&#xa0;mm Hg (CI: 8.0, 7.2), and 50.0&#xa0;mg/dL (95% CI: 54.6, 45.5), respectively and were statistically significant [<xref ref-type="bibr" rid="B46">46</xref>].</p>
</sec>
</sec>
<sec id="s3-3">
<title>Causal explanations of CMO configurations and program theory refinement</title>
<p>The key causal links involved in the management of DM and/or HTN The key causal links involved in the management of DM and/or HTN based on three reinforcing loops and two balancing loops, and the mechanisms of four CMO configurations are presented in an updated CLD (<xref ref-type="fig" rid="F2">Figure 2</xref>).</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Causal relationships of factors influencing the management of Diabetes Mellitus (DM) and/or Hypertension (HTN). Balancing loops (B), Reinforcing loops (R), the mechanisms of identified configurations (green arrows &#x3d; related to CMO1, blue arrow &#x3d; related to CMO2, pink arrows &#x3d; related to CMO3, orange arrows &#x3d; related to CMO4) (A realist review to understand the complexity of effective management of type 2 diabetes and hypertension, 2013&#x2013;2023) (low- and middle-income countries).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="phrs-47-1608655-g002.tif">
<alt-text content-type="machine-generated">Causal loop diagram illustrating factors management of diabetes and hypertension, with loops labeled as care coverage, treatment adherence, trust and relatedness, waiting time, workload, and digital health adoption, connected by directional arrows indicating relationships among variables such as patient-provider communication, access, resource mobilization, and healthcare workers&#x2019; knowledge.</alt-text>
</graphic>
</fig>
<p>In the first reinforcing loop (R1), the level of treatment adherence and self-management affects the incidence of complications [<xref ref-type="bibr" rid="B67">67</xref>&#x2013;<xref ref-type="bibr" rid="B71">71</xref>] and further contributes to patients&#x2019; financial costs [<xref ref-type="bibr" rid="B71">71</xref>&#x2013;<xref ref-type="bibr" rid="B75">75</xref>]. Patients&#x2019; awareness and knowledge improve treatment adherence and self-management [<xref ref-type="bibr" rid="B69">69</xref>, <xref ref-type="bibr" rid="B70">70</xref>, <xref ref-type="bibr" rid="B73">73</xref>, <xref ref-type="bibr" rid="B74">74</xref>]. In contrast, poor awareness leads to complicated conditions as patients may only seek care after complications arise. The delay in diagnosis and treatment adherence increases the risk of severe conditions [<xref ref-type="bibr" rid="B76">76</xref>, <xref ref-type="bibr" rid="B77">77</xref>]. However, patient-provider communication and providing patients with sufficient information increase patients&#x2019; awareness and knowledge [<xref ref-type="bibr" rid="B67">67</xref>&#x2013;<xref ref-type="bibr" rid="B71">71</xref>]. This realist review found that CMO4, through patient-centered care, facilitates patient-provider communication, improving patient engagement and health education [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B37">37</xref>, <xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B43">43</xref>&#x2013;<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B49">49</xref>, <xref ref-type="bibr" rid="B50">50</xref>]. Moreover, digital health adoption improves CMO4 [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B63">63</xref>]. CMO1 also enhances patient awareness and education [<xref ref-type="bibr" rid="B56">56</xref>, <xref ref-type="bibr" rid="B61">61</xref>]. Additionally, geographic disparities in many rural and remote areas increase the average distance to health facilities and transportation costs, which negatively influence access [<xref ref-type="bibr" rid="B67">67</xref>, <xref ref-type="bibr" rid="B69">69</xref>&#x2013;<xref ref-type="bibr" rid="B71">71</xref>, <xref ref-type="bibr" rid="B74">74</xref>, <xref ref-type="bibr" rid="B76">76</xref>] and further affect patient treatment adherence. However, this realist review found that the implementation of mHealth and telehealth within the CMO3 configuration addresses geographic disparities and improves access [<xref ref-type="bibr" rid="B60">60</xref>].</p>
<p>The first balancing loop (B1) illustrates that the availability of infrastructure, medicines, and equipment in public health facilities improves the care continuum coverage, including screening, diagnosis, and treatment [<xref ref-type="bibr" rid="B67">67</xref>, <xref ref-type="bibr" rid="B71">71</xref>, <xref ref-type="bibr" rid="B76">76</xref>, <xref ref-type="bibr" rid="B78">78</xref>]. Additionally, adherence to standard clinical guidelines [<xref ref-type="bibr" rid="B67">67</xref>, <xref ref-type="bibr" rid="B76">76</xref>] strengthens the level of care continuum coverage. However, insufficient infrastructure, medicines, and equipment in public health facilities increase the fragmentation of healthcare pathways [<xref ref-type="bibr" rid="B69">69</xref>, <xref ref-type="bibr" rid="B78">78</xref>], decrease care-seeking in public health facilities [<xref ref-type="bibr" rid="B67">67</xref>, <xref ref-type="bibr" rid="B71">71</xref>, <xref ref-type="bibr" rid="B74">74</xref>], and increase care-seeking in private health facilities [<xref ref-type="bibr" rid="B73">73</xref>, <xref ref-type="bibr" rid="B74">74</xref>, <xref ref-type="bibr" rid="B78">78</xref>]. Care-seeking in private health facilities increases costs, and patients may reduce their treatment adherence [<xref ref-type="bibr" rid="B71">71</xref>, <xref ref-type="bibr" rid="B74">74</xref>, <xref ref-type="bibr" rid="B79">79</xref>]. CMO1, through resource pooling and mobilization within the context of cross-sectoral partnerships, strengthens care continuum coverage [<xref ref-type="bibr" rid="B36">36</xref>, <xref ref-type="bibr" rid="B52">52</xref>, <xref ref-type="bibr" rid="B56">56</xref>, <xref ref-type="bibr" rid="B59">59</xref>, <xref ref-type="bibr" rid="B61">61</xref>] and improves the training of healthcare workers [<xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B55">55</xref>, <xref ref-type="bibr" rid="B57">57</xref>&#x2013;<xref ref-type="bibr" rid="B59">59</xref>]. This realist review also found that CMO3, through the implementation of digital health, improves structured healthcare referrals and coordination [<xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B50">50</xref>, <xref ref-type="bibr" rid="B60">60</xref>, <xref ref-type="bibr" rid="B65">65</xref>].</p>
<p>In the second reinforcing loop (R2), the level of trust and relatedness of patients to the healthcare system influences the acceptance of the disease and treatment, which leads to better treatment adherence and self-management [<xref ref-type="bibr" rid="B68">68</xref>]. Patient-provider communication increases trust and relatedness with healthcare workers [<xref ref-type="bibr" rid="B67">67</xref>&#x2013;<xref ref-type="bibr" rid="B69">69</xref>, <xref ref-type="bibr" rid="B74">74</xref>, <xref ref-type="bibr" rid="B79">79</xref>]. This realist review found that CMO4 improves the level of patient-provider communication [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B37">37</xref>, <xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B43">43</xref>&#x2013;<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B49">49</xref>, <xref ref-type="bibr" rid="B50">50</xref>]. In the second balancing loop (B2), waiting time [<xref ref-type="bibr" rid="B70">70</xref>, <xref ref-type="bibr" rid="B71">71</xref>] has a negative effect on care-seeking in health facilities. As a result, it may drive care-seeking in private health facilities [<xref ref-type="bibr" rid="B79">79</xref>]. In addition, the third reinforcing loop (R3) shows patient load that intensifies with waiting time [<xref ref-type="bibr" rid="B69">69</xref>, <xref ref-type="bibr" rid="B71">71</xref>] as one of the drivers of health workers&#x2019; workload [<xref ref-type="bibr" rid="B71">71</xref>]. A low healthcare workers ratio also increases the healthcare workers&#x2019; workload [<xref ref-type="bibr" rid="B76">76</xref>], which influences the level of patient-provider communication and providing patients with sufficient information about their conditions [<xref ref-type="bibr" rid="B69">69</xref>, <xref ref-type="bibr" rid="B79">79</xref>]. CMO3, through the mechanisms of implementation of mHealth and eHealth, increases clinical decentralization and task sharing [<xref ref-type="bibr" rid="B54">54</xref>], which may reduce health workers&#x2019; workload. mHealth also directly improves patient-provider communication [<xref ref-type="bibr" rid="B63">63</xref>].</p>
<p>In addition, the enabling CMOs not only illustrate that they are neither independent nor mutually exclusive but also underline the patterns of interdependency and synergistic behavior that trigger changes in the management of DM and/or HTN [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B51">51</xref>, <xref ref-type="bibr" rid="B52">52</xref>, <xref ref-type="bibr" rid="B65">65</xref>]. For example, we found that digitalized infrastructure and literacy facilitate mechanisms of mHealth and eHealth implementation that enhance patient-provider communication and personalized care, leading to improved patient knowledge and awareness [<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B46">46</xref>].</p>
</sec>
</sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>This realist review identified four overarching CMO configurations of programs targeting DM and/or HTN across various settings in LMICs. The findings show that the contexts comprising digitalized infrastructure and literacy, patient-centered care, integration of disease-specific programs for chronic conditions, and cross-sectoral partnerships moderate the execution of the underlying mechanisms, leading to better health outcomes. This study also examined the key pathways and feedback loops and explored how CMO configurations may influence the management of DM and/or HTN through a CLD, a key tool to operationalize systems thinking.</p>
<p>Digitalized infrastructure and literacy facilitate the mechanisms associated with the implementation of mHealth and eHealth, supporting better access, coordination, and treatment adherence. A realist synthesis in Southeast Asia reported that in rural regions with limited access to healthcare facilities, telehealth has the potential to serve certain healthcare needs of the community, if supported by sufficient technical infrastructure [<xref ref-type="bibr" rid="B80">80</xref>]. mHealth interventions could also improve healthcare in patients with DM and support hard-to-reach individuals; however, racial/ethnic minority groups, older adults, and those with limited health literacy or more depressive symptoms demonstrated the lowest engagement in an mHealth intervention, highlighting the potential for socioeconomic disparities in outcomes [<xref ref-type="bibr" rid="B81">81</xref>]. Evidence from a systematic review suggests that mHealth interventions are associated with clinical improvements in HbA1c in LMICs [<xref ref-type="bibr" rid="B82">82</xref>]. In contrast, a systematic review and meta-analysis in Africa reported inconclusive evidence regarding the effectiveness of mHealth interventions to decrease blood pressure and glycemic control among affected patients [<xref ref-type="bibr" rid="B83">83</xref>]. The successful implementation of digital health technologies necessitates the development of supportive policies, stable electricity infrastructures, affordable mobile internet service, an understanding of the socio-economic and sociocultural beliefs, and improvement of technological literacy [<xref ref-type="bibr" rid="B84">84</xref>&#x2013;<xref ref-type="bibr" rid="B86">86</xref>].</p>
<p>Our findings revealed that patient engagement and health education improve within the context of patient-centered care, where mechanisms of patient-provider communication and personalized care are triggered. An integrative review of patient-centered care for patients with cardiometabolic diseases indicated that patient-centered care is associated with improvements in factors such as communication, patient-practitioner relationships, shared decision making, medication adherence, engagement and responsibility for health, and self-care and care continuity [<xref ref-type="bibr" rid="B87">87</xref>]. Furthermore, a realist review of the management of DM in people with dementia reported that person-centered care triggers mechanisms such as trust, empowerment, and a belief that self-management is achievable and worthwhile [<xref ref-type="bibr" rid="B32">32</xref>]. Our findings also suggest that in the context of patient-centered care, digital health synergizes the mechanisms related to patient-provider communication and personalized care, highlighting that CMOs are interrelated and dependent.</p>
<p>Another overarching CMO configuration that emerged from our analysis was that integration of disease-specific programs for chronic conditions enables the mechanisms of coordinated care, resulting in treatment adherence. However, a systematic review and meta-analysis of studies in South Africa, India, Kenya, and Uganda revealed that integrated models of care for DM/or HTN with any other disease may make little or no difference to quality of life, mortality, control of DM and HTN, and evidence on all health outcomes is significantly uncertain [<xref ref-type="bibr" rid="B88">88</xref>]. In South Africa, the Integrated Chronic Disease Management (ICDM) for HIV, HTN, and DM also demonstrated only a small clinical effect on the control of blood pressure [<xref ref-type="bibr" rid="B64">64</xref>]. This may reflect health system-related contextual limitations in the primary healthcare facilities, including HTN medication stock-outs, malfunctioning blood pressure machines, shortages of healthcare workers, and long patient waiting times [<xref ref-type="bibr" rid="B89">89</xref>].</p>
<p>Lastly, a wide range of cross-sectoral partnerships exists between international, national, and local communities and between public and private sectors. Strengthening collaboration across communities through the active involvement of community members and leadership from local, state, and national public and private sectors is essential [<xref ref-type="bibr" rid="B90">90</xref>]. In this regard, CARDIO4Cities for HTN in Ulaanbaatar in Mongolia, Dakar in Senegal, and S&#xe3;o Paulo in Brazil was facilitated within a context of multisectoral partnerships. Across these cities, common characteristics included increasingly sedentary lifestyles and shifts in dietary patterns [<xref ref-type="bibr" rid="B91">91</xref>]. However, it is essential to account for contextual variations that may drive mechanisms and produce different health outcomes across settings. In Dakar, one study exploring the effectiveness of the cascade of care for HTN in the CARDIO4Cities initiative identified both contextual enablers and barriers. Health system-related constraints included a lack of support for community health workers, overburdened healthcare workers, and low motivation. Additional factors, such as patients&#x2019; trivialization and denial of HTN, as well as traditional gender roles and the strong impact of low socio-economic status, were reported [<xref ref-type="bibr" rid="B92">92</xref>]. Another study in S&#xe3;o Paulo, Brazil, examined the complexity of the management of HTN with a systems thinking lens using a CLD. The research revealed several socio-economic constraints, including distance to healthcare facilities, educational level, and family income, and noted that gender, ethnicity, and the availability of private health insurance could affect access to care. These interrelated contextual factors reflect the complexity involved in HTN treatment access [<xref ref-type="bibr" rid="B93">93</xref>]. In this review, using a systems thinking lens allowed us to move beyond linear explanations of health system components. The resulting program theory suggests that effective management of DM and/or HTN occurs within complex and interdependent causal pathways and feedback loops.</p>
<sec id="s4-1">
<title>Limitations of the review</title>
<p>One key limitation of this review concerns our level of certainty regarding the generalizability of the CMOs to all LMIC settings. Some studies do not explicitly highlight contexts, mechanisms, or the outcomes resulting from the interaction of the contexts and the mechanisms. Therefore, we were unable to extract a comprehensive CMO for these studies. This limitation might arise from insufficient descriptions of CMOs in these studies or other contexts that may contribute to these mechanisms, ultimately influencing the observed outcomes. Additionally, some contexts and mechanisms related to the patients, family, community, and broader socio-cultural dynamics were not in the scope of this review.</p>
</sec>
<sec id="s4-2">
<title>Conclusion</title>
<p>Healthcare services for DM and/or HTN involve complex and interdependent interactions. This realist review provides insights into how beneficial changes in DM and/or HTN management are facilitated by enabling health system-related contextual factors such as digitalized infrastructure and literacy, cross-sectoral partnerships, integration of disease-specific programs for chronic conditions, and patient-centered care. This review suggests designing and implementing effective models of care in LMICs that take into account the interplay of enabling contexts and their triggered mechanisms to address barriers to the management of DM and/or HTN. Moreover, combining a realist approach with a systems thinking lens is recommended for addressing complex issues within health systems.</p>
</sec>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="s5">
<title>Author contributions</title>
<p>FE, DC, FT, and RC conceptualized the research. FE and DC developed the search strategy. FE and AV conducted screening, data extraction, and quality appraisal. FE and DC characterized the results. FE wrote the first draft, and all authors provided feedback and input. All authors contributed to the article and approved the submitted version.</p>
</sec>
<ack>
<p>The authors would like to thank Prof. Don de Savigny, emeritus professor at Swiss Tropical and Public Health Institute (Swiss TPH) for his insightful input to this study.</p>
</ack>
<sec sec-type="COI-statement" id="s7">
<title>Conflict of interest</title>
<p>The authors declare that they do not have any conflicts of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s8">
<title>Generative AI statement</title>
<p>The author(s) declared that generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="supplementary-material" id="s9">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.ssph-journal.org/articles/10.3389/phrs.2026.1608655/full#supplementary-material">https://www.ssph-journal.org/articles/10.3389/phrs.2026.1608655/full&#x23;supplementary-material</ext-link>
</p>
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<supplementary-material xlink:href="DataSheet3.pdf" id="SM3" mimetype="application/pdf" xmlns:xlink="http://www.w3.org/1999/xlink"/>
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</sec>
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