Health system interventions for adults with type 2 diabetes in low- and middle-income countries: A systematic review and meta-analysis

Background Effective health system interventions may help address the disproportionate burden of diabetes in low- and middle-income countries (LMICs). We assessed the impact of health system interventions to improve outcomes for adults with type 2 diabetes in LMICs. Methods and findings We searched Ovid MEDLINE, Cochrane Library, EMBASE, African Index Medicus, LILACS, and Global Index Medicus from inception of each database through February 24, 2020. We included randomized controlled trials (RCTs) of health system interventions targeting adults with type 2 diabetes in LMICs. Eligible studies reported at least 1 of the following outcomes: glycemic change, mortality, quality of life, or cost-effectiveness. We conducted a meta-analysis for the glycemic outcome of hemoglobin A1c (HbA1c). GRADE and Cochrane Effective Practice and Organisation of Care methods were used to assess risk of bias for the glycemic outcome and to prepare a summary of findings table. Of the 12,921 references identified in searches, we included 39 studies in the narrative review of which 19 were cluster RCTs and 20 were individual RCTs. The greatest number of studies were conducted in the East Asia and Pacific region (n = 20) followed by South Asia (n = 7). There were 21,080 total participants enrolled across included studies and 10,060 total participants in the meta-analysis of HbA1c when accounting for the design effect of cluster RCTs. Non-glycemic outcomes of mortality, health-related quality of life, and cost-effectiveness had sparse data availability that precluded quantitative pooling. In the meta-analysis of HbA1c from 35 of the included studies, the mean difference was −0.46% (95% CI −0.60% to −0.31%, I2 87.8%, p < 0.001) overall, −0.37% (95% CI −0.64% to −0.10%, I2 60.0%, n = 7, p = 0.020) in multicomponent clinic-based interventions, −0.87% (−1.20% to −0.53%, I2 91.0%, n = 13, p < 0.001) in pharmacist task-sharing studies, and −0.27% (−0.50% to −0.04%, I2 64.1%, n = 7, p = 0.010) in trials of diabetes education or support alone. Other types of interventions had few included studies. Eight studies were at low risk of bias for the summary assessment of glycemic control, 15 studies were at unclear risk, and 16 studies were at high risk. The certainty of evidence for glycemic control by subgroup was moderate for multicomponent clinic-based interventions but was low or very low for other intervention types. Limitations include the lack of consensus definitions for health system interventions, differences in the quality of underlying studies, and sparse data availability for non-glycemic outcomes. Conclusions In this meta-analysis, we found that health system interventions for type 2 diabetes may be effective in improving glycemic control in LMICs, but few studies are available from rural areas or low- or lower-middle-income countries. Multicomponent clinic-based interventions had the strongest evidence for glycemic benefit among intervention types. Further research is needed to assess non-glycemic outcomes and to study implementation in rural and low-income settings.


Rationale
3 Describe the rationale for the review in the context of what is already known. Introduction, paragraphs 1-3 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
Methods section, paragraph 1 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.
"Search strategy and selection criteria" section, paragraphs 1-3 Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.
"Search strategy and selection criteria" section, paragraph 1 Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

S3 Appendix
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).
"Data analysis" section, paragraph 1 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.
"Data analysis" section, paragraph 1 Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.
"Data analysis", paragraph 1 Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). "Statistical analysis" section, paragraph 1 Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.
"Statistical analysis" section, paragraphs 1-2 and caption of forest plot in Figure 2 Page 1 of 2

Section/topic # Checklist item Reported on page #
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).
"Statistical analysis" section, paragraph 2 Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.
"Overview of results" section and Figure 1 Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

S5 Appendix
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). S7 Appendix and "Risk of bias and sensitivity analysis" section paragraph 2 Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).
Discussion, paragraph 1 Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias). For more information, visit: www.prisma-statement.org.