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Evidence review D for periodontal treatment to improve diabetic control in adults with type 1 or type 2 diabetes
Evidence review D
NICE Guideline, No. 17
1. Periodontal treatment to improve diabetic control in adults with type 1 or type 2 diabetes
1.1. Review question
In adults with type 1 or 2 diabetes, what is the effectiveness of periodontal treatment to improve diabetic control?
1.1.1. Introduction
Diabetes and periodontitis are two chronic, highly prevalent comorbid conditions in general population that have long been considered to be bidirectionally linked. Research shows that hyperglycaemia and resultant advanced glycation end product formation, as one of several pathways that leads to the microvascular and macrovascular complications of diabetes, is also involved in the pathophysiology of periodontitis in people with diabetes. However, a growing body of scientific evidence also supports the fact that the periodontal infection adversely affects glycaemic control.
Periodontal inflammation if left untreated or inadequately controlled, could not only progress to a moderate or severe periodontitis, but could also result in increased systemic inflammatory burden, further worsening glycaemic status and perpetual promotion of associated complications of diabetes. Thus, establishing the effectiveness of periodontal treatment on glycosylated haemoglobin (HbA1c) levels is important to help to reduce the harms associated with oral diabetes complications.
This evidence review aims to assess the effectiveness of periodontal treatment for improving diabetic control in adults with type 1 or type 2 diabetes. The economic costs of periodontal treatment were also considered.
As part of a collaboration between the NICE Guideline Development Team and Cochrane, the evidence presented in this review was provided by Cochrane Oral Health (COH) and is drawn from their recently published systematic review (Simspon et al., 2022).
We thank Cochrane Oral Health for their assistance in providing the literature searches and data for the review question relating to the Type 1 diabetes in adults: diagnosis and management guideline and the Type 2 diabetes in adults: management guideline.
1.1.2. Summary of the protocol
This review identified studies that fulfilled the conditions listed in Table 1, as specified in the protocol developed in agreement with the committee members. For full details of the review protocol, see Appendix A.
The Cochrane group did not publish a new protocol specifically for their systematic review as this work was carried out as a continuation of earlier systematic reviews (Simpson et al., 2015; Simpson et al., 2010) with no substantive changes to the existing protocol (Simpson et al., 2004).
1.1.3. Methods and process
This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in Appendix A and the methods section in Appendix B.
As part of the collaboration, the COH performed:
- the literature search, screening of records, and study selection
- data extraction and production of evidence tables
- risk of bias of assessment of included studies against the following risk of bias criteria: random sequence generation; allocation concealment; blinding of participants; blinding of clinical operators; blinding of periodontal outcome assessors; incomplete outcome data; selective outcome reporting; other potential biases (using the Cochrane’s RoB tool)
- publication bias assessment using funnel plots
- data analysis, including pairwise meta-analyses, subgroup analyses and narrative synthesis of findings.
The NICE Guideline Development Team followed the NICE Methods and further performed:
- overall quality assessment and classification of each individual RCTs into low, moderate and high risk of bias
- directness assessment of each individual study based on concerns about the population, intervention, comparator and/or outcomes in the study and how directly these variables could address the specified review question (studies rated as direct, partially direct or indirect)
- quality assessment of the quality of the Cochrane Review using the ROBIS checklist for systematic reviews and meta-analysis of interventional studies and its applicability as the primary source of data
- alterations to the Cochrane Review meta-analyses to reflect the methodology used by the NICE Guideline Development Team
- GRADE for pairwise meta-analyses of interventional evidence to assess the quality of evidence of selected outcomes.
All alterations made by the NICE team are clearly stated in the relevant sections. In particular, the choice of random effects models presented in the Cochrane Review has been altered in the GRADE tables depending on the degree of heterogeneity of the assembled evidence to reflect NICE methodology specified in Appendix B. The GRADE analyses used to assess the quality of evidence for a specific outcome across studies using MIDs differs from the Cochrane methods which has reflected in differences in the interpretation of the quality of evidence between the COH systematic review and the ones presented in this evidence review
Permission to reproduce and include additional material and analysis from the Cochrane review content was made as per the terms of the Collaboration Agreement for published evidence review collaboration stated in the section 2.1 Principles of fair use of Cochrane reviews in NICE guidelines of the Guideline support document: Cochrane reviews and NICE guideline development.
The comparison of interest was periodontitis treatment versus no active treatment or usual care. The COH formed three subgroups for the intervention: subgingival instrumentation also known as scaling and root planing (SRP), non-surgical periodontal treatment or mechanical debridement SRP in combination with systemic or locally delivered antimicrobial as adjunctive treatment; and SRP combined with antimicrobial mouth rinse as adjunctive treatment. The data for these subgroups are presented at 3 follow-up time points: 3-4 months, 6 months, and 12 months.
For the primary outcome HbA1c, a subgroup analysis on provision of maintenance treatment following the initial periodontal treatment versus no maintenance treatment for studies lasting longer than three months was conducted.
Other subgroups that the NICE Committee identified as relevant to this evidence review e.g., subgrouping by diabetes type (type 1 vs type 2); diabetic control: poor (HbA1c above 8.5%) versus fair (HbA1c from 7.5 to 8.4%) versus good (HbA1c up to 7.5%); rural/urban setting etc., could not be analysed due to insufficient and/or low quality of data.
The format of the available data did not allow pooling of secondary outcomes (adverse events and QoL) and these have been narratively synthesised.
Declarations of interest were recorded according to NICE’s conflicts of interest policy.
1.1.4. Clinical effectiveness evidence
1.1.4.1. Included studies
In the current draft update, the COH identified 3109 records through updated database searching and 40 records identified through the previous version of the review. After deduplication, 2102 records were screened at title and abstract stage. 2030 records were discarded as they did not fulfil the review inclusion criteria. 72 records were sourced for full text screening. Of these, 15 full-text articles (11 trials) were excluded with reasons while 4 full-text articles were classified as ongoing studies. After the full text screening, 35 studies (reported in 53 publications) involving 3249 randomised participants in total fulfilled the eligibility criteria and were included for narrative synthesis; 33 of the studies (reported in 51 publications) were included in one or more meta-analyses. All studies were parallel randomised controlled trials (RCTs).
The last search was conducted on the 7th of September 2021 and the search strategy is presented in Appendix C. The PRISMA diagram for the study selection process is included in Appendix D. The evidence tables of the included studies are presented in Appendix E. Additional searches by the NICE Guideline Development Team were not performed.
1.1.4.2. Excluded studies
All excluded references with reasons for exclusion are given in Appendix K. This appendix also includes the references of ongoing studies.
1.1.5. Summary of clinical studies included in the effectiveness evidence
As a result of these exclusions, the Cochrane review included 35 parallel RCTs in its narrative synthesis and 33 studies in the quantitative synthesis 33 studies included participants with confirmed diagnosis of type 2 diabetes; 1 study assumed participants to all be type 2 diabetes without confirmed diagnosis (Jones 2007). 1 study included participants with either type 1 or type 2 diabetes (Vergnes 2018).
There was substantial variation in both the level and range of HbA1c of participants at baseline, with consequent variation in the potential for improvement in glycaemic control as a result of the intervention. Most studies were mixed and involved participants with good (HbA1c up to 7.5%), fair (HbA1c from 7.5 to 8.4%) and/or poor (HbA1c over 8.5%) metabolic control. The use of antidiabetic therapy and whether this was changed during the study conduct period varied across the trials. The severity of periodontitis also varied across studies, with some including people with mild to moderate periodontitis, some with moderate to severe periodontitis and some including the full range.
21 studies assessed the effects of SRP versus no treatment/ usual care, 11 studies assessed SRP plus systemic or locally delivered antimicrobial versus no treatment/usual care and 3 studies assessed SRP plus antimicrobial mouth rinse (chlorhexidine) vs no treatment/ usual care 4 studies included supragingival scaling as part of usual care (Koromantzos 2011; Mauri-Obradors 2018; Mizuno 2017; Rodrigues 2015).
Most of the studies (30) measured the outcomes at 3-4 months. For the 11 studies that reported data at 6 months, maintenance was provided following the initial periodontal treatment in 8 studies, with 3 studies not providing maintenance. Only one study reported outcomes at 12 months (D'Aiuto 2018
All 35 studies reported data on HbA1c. However, 2 included studies did not present results for HbA1c in a way that allowed them to be used in meta-analysis (Artese 2015; Rapone 2021) and thus were excluded from the quantitative synthesis. Clinical attachment loss was reported in 19 studies and probing pocket depth in 24 studies.
7 studies reported some adverse events (D'Aiuto 2018; Jones 2007; Koromantzos 2011; Mauri-Obradors 2018; Qureshi 2021; Tsobgny-Tsague 2018; Vergnes 2018) and 6 studies reported that there were no adverse effects (Chen 2012; Das 2019; El-Makaky 2020; Engebretson 2013; Mizuno 2017; Singh 2008). The remainder (22 studies) did not report whether there were any adverse events or not.
3 included studies reported data relating to QoL (D'Aiuto 2018; Mizuno 2017; Vergnes 2018) using different validated questionnaires.
All studies were at high risk of bias for blinding of participants and clinical operators as this could not be avoided in the trials due to the nature of interventions. A funnel plot of the 30 included studies that assessed HbA1c at 3-4 months failed to indicate any relationship between mean percentage reduction in HbA1c and precision (related to sample size) and no presence of publication bias was observed.
The NICE technical team judged the Cochrane systematic review as being fully applicable and of a high quality and it was used as the primary source of data (for details see the methods section in Appendix B).
The detailed evidence tables, the resulting summaries of risks of bias and publication bias, and assessment of the Cochrane systematic review and study applicability to this evidence review are all presented in Appendix E. Included studies are referenced in full in section 1.1.12 References. The NICE’s assessment of study applicability to the review protocol and the ROBIS summary are presented in Appendix D, following the funnel plot of publication bias assessment.
1.1.6. Summary of the clinical effectiveness evidence
1.1.6.1. Primary outcomes:
The forest plots of the analyses of primary outcomes included in the GRADE tables are presented in Appendix F, with the GRADE tables in Appendix G. Studies were grouped based on the outcome, follow-up time and type of periodontal intervention, and the provision of maintenance treatment following initial intervention. Situations where the data are consistent, at a 95% confidence level, with an effect in one direction (i.e. one that is 'statistically significanť) it is stated that the evidence showed an effect. Where the 95% CI crosses the line of no effect, the evidence could not differentiate between the comparators.
Results for the individual subgroups are reported when there was evidence of between group heterogeneity (for details see the methods section in Appendix B). The summaries of GRADE tables are presented below:
For studies reporting data at 6 months, a subgroup analysis for HbA1c was conducted based on the provision of maintenance treatment following the initial periodontal treatment. The results of the subgroup analysis are presented in Table 5. There was no evidence of a difference between the subgroups (P = 0.58) and differences in the provision of maintenance did not explain the heterogeneity.
1.1.6.2. Secondary outcomes
Due to insufficient data and the format presented, secondary outcomes were not meta-analysed and were narratively synthesised.
Adverse effects
7 studies reported adverse events (D'Aiuto 2018; Jones 2007; Mauri-Obradors 2018; Vergnes 2018; Koromantzos 2011; Qureshi 2021; Tsobgny-Tsague 2018). These studies suggested their participants in the intervention group experienced minor side effects such as more soreness, tenderness, pain and thermal sensitivity than the control group; these are common sequelae of SRP. The most reported symptoms among those taking systemic or locally delivered antimicrobials were diarrhoea, abdominal pain, and nausea. For participants using antibacterial mouth rinse, the most common complaints were oral disorders: changes in taste, tooth staining, and sore mouth or tongue tip irritation. Swelling of the face, lips, and throat and shortness of breath were also reported.
6 studies reported that there were no adverse effects: Chen 2012; Das 2019 (reported no adverse effects from use of doxycycline but did not mention other aspects of interventions), El-Makaky 2020 ("no significant side effects"), Engebretson 2013, Mizuno 2017 ("no serious study-related adverse events"), and Singh 2008 (reported no adverse effects from use of doxycycline but did not mention other aspects of interventions).
Quality of life (QoL)
The available evidence from the three studies that measured QoL as an outcome is sparse and mixed as studies have used different standardised questionnaires to measure it. However, there is some limited evidence of a possible benefit from periodontal treatment in terms of QoL related to some aspects of living with diabetes and periodontitis.
1.1.7. Economic evidence
1.1.7.1. Included studies
A systematic literature search was undertaken to identify published health economic evidence relevant to the review questions. Studies were identified by searching EconLit, Embase, CRD NHS EED, International HTA database, MEDLINE, PsycINFO and NHS EED. All searches were updated on 4th November 2021, and no papers published after this date were considered. This returned 1,542 references (see Appendix C for the literature search strategy). After deduplication and title and abstract screening against the review protocol, 1,540 references were excluded, and 3 references were ordered for screening based on their full texts.
Of the 3 references screened as full texts, one study was a systematic review which was investigated as a source of references; however, no cost-utility studies were included. In total there were two studies that contained cost-utility analyses evaluating non-surgical periodontal treatment. One UK study was included in this evidence review in full as the most relevant evidence, with the other being excluded as not sufficiently applicable to the UK context. The health economic evidence study selection is presented as a flowchart in Appendix H. Full economic evidence tables along with the checklists for study applicability and study limitations are shown in Appendix I.
1.1.7.2. Excluded studies
Studies excluded in the full text review, together with reasons for exclusion, are listed in Appendix K.
1.1.8. Summary of included economic evidence
The only relevant study identified assessed the cost-effectiveness of non-surgical periodontal treatment for people with periodontitis with newly diagnosed type 2 diabetes. Solowiej-Wedderburn et al (2017) found non-surgical periodontal treatment to be cost-effective at the £30,000 cost-effectiveness threshold.
1.1.9. Economic model
An original cost-effectiveness analysis was undertaken for this review question. A summary is included here, with the full analysis available in the economic model report.
Model structure
The economic analysis was done using the IQVIA CORE Diabetes model (CDM) version 9.5. IQVIA CDM is a Markov simulation model predicting the progression of diabetes over time using a series of interlinked and interdependent Markov sub models for diabetes related complications. The model can be run over different time horizons including the lifetime of a patient. The model has been previously validated against epidemiological and clinical studies of type 1 and type 2 diabetes. A more detailed description of IQVIA CDM has been published by Palmer et al (2004). The model allows for transition probabilities and management strategies to be differentiated by type of diabetes. Due to the model structure our analysis for type 1 diabetes and type 2 diabetes were conducted separately. Diabetes type specific data were used for baseline characteristics, diabetes progression and complications.
Diabetes progression with the IQVIA CDM is simulated using a series of interlinked, interdependent sub-models which simulate the following complications:
- angina
- myocardial infarction
- congestive heart failure
- stroke
- peripheral vascular disease
- diabetic retinopathy
- macular oedema
- cataract
- hypoglycaemia
- ketoacidosis
- lactic acidosis
- nephropathy and end-stage renal disease
- neuropathy
- foot ulcer
- amputation
- non-specific mortality
The Markov sub models listed above use time, state, and diabetes type-dependent probabilities from published sources. Interactions between these sub models are moderated by employing Monte Carlo simulations using tracker variables.
The analysis simulates the use of non-surgical periodontal treatment compared to no treatment. The analysis is separated by type 1 and type 2 diabetes, although treatment is assumed to have the same efficacy between the two populations.
Analysis
A cohort of people with type 1 and type 2 diabetes were defined using patient demographics, racial characteristics, baseline risk factors, and baseline complications to reflect an adult type 1 diabetes and type 2 diabetes population in the UK. The analysis was performed across a lifetime horizon. Costs and quality-adjusted life years (QALYs) were considered from a UK NHS perspective. The analysis follows the standard assumptions of the NICE reference case including discounting at 3.5% for costs and health effects.
Treatment effectiveness was characterised by a reduction in HbA1c levels. Effectiveness evidence was pooled across both type 1 and type 2 studies. This value was then used to adjust the HbA1c level for usual care value which was different in type 1 and type 2 diabetes. All periodontal treatments have been pooled because there is limited clinical evidence for this comparison.
UK specific sources were identified model inputs relating to costs, utilities, and other management parameters. In cases where UK specific sources were not available, default IQVIA CDM parameters were used. Treatment specific costs were calculated using published national sources.
Results
The base case results for people with type 1 diabetes (Table 7) showed that periodontal treatment compared with usual care was cost-effective. Periodontal treatment results in both an increase in QALYs and a decrease in costs meaning treatment dominates compared with usual care.
The base case results for people with type 2 diabetes (Table 8) showed that treatment compared with usual care was cost-effective at a threshold of £20,000 per QALY.
1.1.10. The committee's discussion and interpretation of the evidence
1.1.10.1. The outcomes that matter most
The committee agreed that HbA1c, Clinical Attachment Level (CAL) and Probing Pocket Depth (PPD) are important outcomes to assess the link between diabetes and periodontitis. Successful periodontal treatment leads to reduction in HbA1c, CAL and PPD and consequently improved Quality of Life (QoL) which was considered a secondary outcome.
Adverse effects were thought to be less important due to the nature of conventional nonsurgical periodontal treatment which generally causes only minor discomfort and tooth sensitivity that normally resolves after a few days.
1.1.10.2. The quality of the evidence
The certainty of the body of evidence for the effect of periodontal treatment on diabetic control ranged from very low to moderate, however, several factors were considered when linking the evidence to recommendations.
There was substantial variation in inclusion criteria at baseline, with consequent variation in the potential for improvement in glycaemic control as a result of the intervention. All studies included participants with type 2 diabetes with only one study including participants with either type 1 or type 2 diabetes and lack of studies on type 1 diabetes was acknowledged. Most studies involved mixed participants with HbA1c ranging from 6%-14%, diabetic control classified as poor (HbA1c above 8.5%), fair (HbA1c from 7.5 to 8.4%) and good (HbA1c up to 7.5%) and severity of periodontitis ranging from mild-to-moderate, moderate, moderate-to-severe and severe.
The committee agreed to not downgrade the quality of the studies for lack of blinding of participants and clinical operators, as this was not thought to be feasible when knowledge of the intervention is inherent to its use. Also, the committee agreed that for the primary outcome HbA1c, performance and detection bias (blinding of periodontal assessors) was not relevant, as HbA1c tests were carried out remotely.
The subgroup analyses (based on intervention type and provision of a maintenance periodontal treatment for studies longer than 3 months) could not explain the substantial heterogeneity among studies, and it was agreed that the possible cause is the substantial variation in both the level and range of HbA1c, and severity of periodontitis at baseline. The committee also acknowledged that subgrouping based on metabolic control at baseline could not be meaningfully done with the available data.
Only three studies provided evidence on QoL. As all used different standardised tools e.g., assessing either diabetes or oral health QoL measures, no clear conclusions on QoL could be drawn. Adverse events were rarely assessed but the studies that measured adverse effects generally reported no or mild adverse effects, and any serious adverse events were similar in intervention and control arms. The dental healthcare professionals co-opted to the committee noted that these findings reflected their own clinical experience.
Combined with the positive health economic results, the committee concluded that the clinical evidence base had a consistent and adequate volume of effectiveness to justify the recommendation of periodontal treatment in people diagnosed with diabetes and periodontitis.
Despite of the lack of evidence especially on type 1 diabetes and QoL, the committee did not make any recommendations for future research. It was thought the findings based on type 2 diabetes were applicable to people with type 1 diabetes and future research was unlikely to change these conclusions.
1.1.10.3. Benefits and harms
The committee acknowledged the benefits of periodontal treatment in improving diabetes control in adults with type 1 and type 2 diabetes. Although most of the research has focused on type 2 diabetes mellitus, the committee thought that that the evidence on the link between increased HbA1c and periodontitis is applicable to people with type 1 diabetes mellitus as well. The committee members agreed that all people with diabetes are at increased risk of developing periodontitis and stated that this should be routinely discussed as a potential complication of diabetes alongside eye disease and diabetes related foot problems.
The pooled effect of periodontal treatment when compared to no active intervention or usual care demonstrated that the treatment of periodontitis using subgingival instrumentation/ scaling and root planing improved all primary outcomes (HbA1c, Clinical Attachment Level and Probing Pocket Depth).
The few studies that measured adverse effects generally reported no or mild adverse effects. However, the committee members, based on their own clinical experience, agreed that most reported adverse effects resulting from periodontal treatment are not serious and increased soreness, tenderness, pain, and thermal sensitivity are common sequelae of subgingival instrumentation/ scaling and root planing. The committee acknowledged that the evidence of the possible benefit of periodontal treatment in terms of health-related quality of life was limited.
Overall, it was agreed that the benefits outweigh the minor side effects and the treatment of periodontitis using conventional non-surgical techniques should be recommended to improve diabetic control. The decision about which periodontal treatment to perform would be made by the dental healthcare professional during oral health reviews in line with the NICE clinical guideline CG19. To prevent and manage periodontitis, advice on regular oral health reviews, and maintaining good oral health hygiene was suggested in the long term. The frequency of the oral health reviews should be advised by a dental practitioner and be personalised to the individual’s oral health needs as outlined in the NICE guideline on dental checks: intervals between oral health reviews. Lastly, for prevention of periodontitis and oral health advice, a reference to the NICE’s guidance on oral health promotion was made. In support of the proposed recommendations, the committee also referred to the NHS England commissioning standard: Dental Care for People with Diabetes which should ensure that people with diabetes can access effective oral healthcare services with the aim of improving their oral health.
1.1.10.4. Cost-effectiveness and resource use
The committee noted there was only one published economic study in the UK context, which found non-surgical periodontal treatment might be cost-effective among people with type 2 diabetes. The results were sensitive to changes in the baseline HbA1c level, age, rates of adherence response to the treatments. The key limitation is that the study only focused on type 2 diabetes and did not carry out probabilistic sensitivity analysis to account for the joint uncertainty in model inputs. Therefore, we adopted a more comprehensive modelling structure (IQVIA Core Diabetes Model) based on the most updated clinical evidence to assess the cost-effectiveness of non-surgical periodontal treatments for improving HbA1c control in people with either type 1 or type 2 diabetes.
The committee generally agreed with the underlying assumptions for the cost and utility inputs. They raised some concerns over removing patient co-payments from the overall cost, since it did not take into account affordability of the treatment and inequality in the access to dental care. However, the committee also noted that the cost-effectiveness analysis was undertaken from an NHS perspective, and only costs incurred by health care sector and public sectors should be included in the analysis. To address the concerns about affordability among people from lower socio-economic backgrounds, we added an additional scenario in the sensitivity analyses to include the full cost of the treatment (no co-payment was deducted). The results remained cost-effective at the £30,000 per QALY threshold. Therefore, even with the increasing proportion of people who are exempt from dental charges, periodontal treatments could still be cost-effective for the NHS.
The committee acknowledged the fact that the model only considered diabetes-related outcomes (reduction in HbA1c) and did not take dental outcomes into account. Our model structure did not contain a dental module that can be used to model the costs and consequences along the periodontal pathway of intervening with treatment in a cohort of people with diabetes. In addition, the commonly adopted utility measure, EQ-5D, is not sufficient to capture the processes and outcomes of dental care due to its insensitivity and short health state durations. There are also no good mapping algorithms to translate disease specific measures (e.g. Oral Health Impact Profile) onto utility values. Given that periodontal treatment appears highly cost-effective in our base case analysis, the inclusion of any potential oral health benefit will further increase its cost-effectiveness and will not influence our conclusions.
The committee recognised that periodontal treatment is cost-effective for people with type 1 and type 2 diabetes in the base case analysis, and the results remain robust across most scenarios in the sensitivity test. Although the treatment appears not cost-effective under some scenarios (e.g. shorter time horizon, lower compliance/response rate, reduced treatment benefit over time), the committee felt that these were extreme cases and unlikely to reflect the real-world practice. In addition, the committee discussed about the potential resource impact and agreed that the new recommendations will increase health professionals’ awareness of periodontitis among people with diabetes. This might lead to a short-term increase in the number of dental appointments, but the associated cost increase is likely to be overweighed by the long-term benefits in the improvement of dental and diabetic outcomes.
1.1.10.5. Other factors the committee took into account
The committee agreed that to help prevent or manage periodontitis among people with diabetes enhanced advice and continuing educational support is necessary. The multidisciplinary approach would be a step forward towards achieving comprehensive care and has the potential to improve consistency in service delivery and consequently diabetes control and oral health outcomes.
The committee acknowledged that the terms used to refer to the non-surgical periodontal treatment such as scaling, polishing etc. are now historic terms and no longer in use as per the new periodontal disease nomenclature. However, to increase acceptance among the target population, these terms have not been replaced to reflect the new terminology, as these are still widely recognised by the public.
The committee wished to stress that NHS dental services are free only for pregnant women or women who have had a baby in the last 12 months and those receiving low-income benefits and thus wished to highlight the increased risk of periodontitis and the needs of certain groups with diabetes. The committee noted that people from lower socio-economic and disadvantaged groups (e.g., e.g., homeless people and Gypsy, Roma and Traveller communities)) may experience difficulties in accessing higher-cost periodontal treatment. In this case, to reduce inequality the provision of fee-free periodontal treatment was suggested. The committee also considered the needs of certain groups such as people with frailty, people with physical disability, mental health related or learning disability. These groups may also have limitations with their dexterity and compliance which can cause difficulties in using toothbrushes or interdental and interproximal brushes to maintain good oral hygiene and this may diminish the effect of periodontal treatment over time. The committee highlighted that these groups may not tolerate dental care and general anaesthetics might be needed to perform periodontal treatment. This would potentially require palliative periodontal care to avoid repeated general anaesthetics. Consideration for prisoners/ detainees was also stressed, as access to interdental and/or interproximal brushes and other dental health care products is limited in these settings for security reasons. The committee highlighted racial or ethnic disparities, e.g., higher prevalence and increased risk of severe periodontitis among the Black, African and Asian community. Overall, access to adequate dental treatment/ oral health reviews and personal oral hygiene products in combination with proactive engagement and enhanced educational support have the potential to reduce inequalities among disadvantaged groups.
Lastly, how the delivery of care for people with diabetes is best integrated across healthcare settings was considered. Following the publication of this guideline, the committee members discussed the uncertainty regarding the initial increase in referrals of people with diabetes for dental checks and oral health reviews as this will potentially impact on the scarce NHS dental service. Clear advice from the oral healthcare/ dental teams, of what is expected of them regarding diabetes dental care and clear care pathways are necessary to enhance the quality of care across the continuum and improve service delivery. In line with the NHS England commissioning standard: Dental Care for People with Diabetes, the committee agreed it is expected that the majority of general dental providers will be able to deliver level 1 services to diagnose and manage patients with uncomplicated periodontitis but access to level 2 dental services was uncertain. The committee members were also uncertain how this would impact on dental and oral health services in the long term, as this would depend on the frequency of oral health reviews as advised by the oral healthcare/ dental team and personalised to the individual’s oral health risk, individual’s compliance and the capacity of dental services. The long-term impact becomes even more complicated considering population demographics and increasing prevalence of the two chronic conditions (diabetes and periodontitis). Overall, current lack of access to NHS dentistry and gaps in periodontal services, especially treatment of severe periodontal cases (e.g., lack of access to dental hospitals across the country) and future provision of periodontal treatment was of major concern, warranting a broader and more flexible dental care access and services.
1.1.11. Recommendations supported by this evidence review
This evidence review supports recommendations 1.15.1 to 1.15.4 of the Type 1 diabetes in adults: diagnosis and management guideline and recommendations 1.7.1 to 1.7.4 of the Type 2 diabetes in adults: management guideline.
1.1.12. References
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Calbacho V, Carrasco E, Wilckens M, Barboza P, Grant C, Aguirre M, et al Evaluation of influence of conventional therapy in diabetics type 2. Journal of Dental Research 2004;84((Spec Iss B) Chilean section):65739.Chen 2012
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D'Aiuto 2018
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Das 2019
Das AC, Das SJ, Panda S, Sharma D, Taschieri S, Fabbro MD. Adjunctive effect of doxycycline with conventional periodontal therapy on glycemic level for chronic periodontitis with type 2 diabetes mellitus subjects. Journal of Contemporary Dental Practice 2019;20(12):1417–23. [PMID: 32381843] [PubMed: 32381843]El-Makaky 2020
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Engebretson S, Gelato M, Hyman L, Michalowicz BS, Schoenfeld E. Design features of the Diabetes and Periodontal Therapy Trial (DPTT): a multicenter randomized single-masked clinical trial testing the effect of nonsurgical periodontal therapy on glycosylated hemoglobin (HbA1c) levels in subjects with type 2 diabetes and chronic periodontitis. Contemporary Clinical Trials 2013;36(2):515–26. [PMC free article: PMC3885354] [PubMed: 24080100]- Engebretson S, Michaelowicz B, Seaquist ER, Reddy M, Lewis CE, Oates T, et al The Diabetes and Periodontal Therapy Trial (DPTT). Journal of Dental Research 2012;91(Suppl A (AADR 41st Annual Meeting; Tampa, Florida)):Abstract No 568.
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Felipe 2015
Felipe MEMC. Effect of non-surgical periodontal treatment on glycemic control, inflammatory mediators and adipokines in patients with type 2 diabetes and severe chronic periodontitis (Thesis) [Efeito do tratamento periodontal não-cirúrgico sobre o controle glicêmico, mediadores inflamatórios e adipocinas em pacientes com diabetes mellitus tipo 2 e periodontite crônica severa ]. Rio de Janeiro 2015;pesquisa.bvsalud.org /portal/resource/pt/biblio-910208 (accessed 1 September 2021). Gay 2014 {published data only}
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*Koromantzos PA, Makrilakis K, Dereka X, Katsilambros N, Vrotsos IA, Madianos PN. A randomized, controlled trial on the eEect of non-surgical periodontal therapy in patients with type 2 diabetes. Part I: effect on periodontal status and glycaemic control. Journal of Clinical Periodontology 2011;38(2):142–7 [PubMed: 21114680]- Koromantzos PA, Makrilakis K, Dereka X, OEenbacher S, Katsilambros N, Vrotsos IA, et al Effect of non-surgical periodontal therapy on C-reactive protein, oxidative stress, and matrix metalloproteinase (MMP)-9 and MMP-2 levels in patients with type 2 diabetes: a randomized controlled study. Journal of Periodontology 2012;83(1):3–10. [PubMed: 21627458]
Kothiwale 2013
Kothiwale SV, Kothiwale VA, Bhargava PV. Effect of non-invasive periodontal therapy on glycaemic control in type 2 diabetes mellitus patients - a randomized control trial. Diabetes 2013;62(Suppl 1):Abstract No A229.Lee 2020
Lee JY, Choi YY, Choi Y, Jin BH. Efficacy of non-surgical treatment accompanied by professional toothbrushing in the treatment of chronic periodontitis in patients with type 2 diabetes mellitus: a randomized controlled clinical trial. Journal of Periodontal Implant Science 2020;50(2):83–96. [DOI: 10.5051/jpis.2020.50.2.83] [PMID: 32395387] [PMC free article: PMC7192821] [PubMed: 32395387] [CrossRef]Li 2011
Li Z, Sha YQ, Zhang BX, Zhu L, Kang J. [Effect of community periodontal care intervention on periodontal health and glycemic control in type 2 diabetic patients with chronic periodontitis]. [Chinese]. Beijing da Xue Xue Bao (Yi Xue Ban/ Journal of Peking University. Health Sciences) 2011;43(2):285–9. [PubMed: 21503128]Mauri-Obradors 2018
Mauri-Obradors E, Merlos A, Estrugo-Devesa A, Jané-Salas E, López-López J, Viñas M. Benefits of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and chronic periodontitis: a randomized controlled trial. Journal of Clinical Periodontology 2018;45(3):345–53. [DOI: 10.1111/jcpe.12858] [PMID: 29265454] [PubMed: 29265454] [CrossRef]Mizuno 2017
Mizuno H, Ekuni D, Maruyama T, Kataoka K, Yoneda T, Fukuhara D, et al The effects of non-surgical periodontal treatment on glycemic control, oxidative stress balance and quality of life in patients with type 2 diabetes: a randomized clinical trial. PLoS One 2017;12(11): e0188171. [DOI: 10.1371/journal.pone.0188171] [PMCID: PMC5689834] [PMID: 29145468] [PMC free article: PMC5689834] [PubMed: 29145468] [CrossRef]Moeintaghavi 2012
Moeintaghavi A, Arab HR, Bozorgnia Y, Kianoush K, Alizadeh M. Non-surgical periodontal therapy aEects metabolic control in diabetics: a randomized controlled clinical trial. Australian Dental Journal 2012;57(1):31–7. [PubMed: 22369555]Qureshi 2021
Qureshi A, Bokhari SA H, Haque Z, Baloch AA, Zaheer S. Clinical efficacy of scaling and root planing with and without metronidazole on glycemic control: three-arm randomized controlled trial. BMC Oral Health 2021;21(253). [DOI: 10.1186/s12903-021-01620-1] [PMC free article: PMC8113795] [PubMed: 33980234] [CrossRef]Raman 2014
Raman RP, Taiyeb-Ali TB, Chan SP, Chinna K, Vaithilingam RD. Effect of nonsurgical periodontal therapy versus oral hygiene instructions on Type 2 diabetes subjects with chronic periodontitis: a randomised clinical trial. BMC Oral Health 2014;14(1):2–19. [PMC free article: PMC4082680] [PubMed: 24965218]Rapone 2021
Rapone B, Ferrara E, Corsalini M, Qorri E, Converti I, Lorusso F, et al Inflammatory status and glycemic control level of patients with type 2 diabetes and periodontitis: a randomized clinical trial. International Journal of Environmental Research and Public Health 2021;18(6):3018. [DOI: 10.3390/ijerph18063018] [PMID: 33804123] [PMC free article: PMC7998112] [PubMed: 33804123] [CrossRef]Rodrigues 2015
Rodrigues RM J. Effect of periodontal therapy on serum osteocalcin levels in patients with type 2 diabetes and severe chronic periodontitis [Efeito do tratamento periodontal nos niveis de osteocalcina serica em pacientes com diabetes tipo 2 e periodontite cronica severa [thesis]]. Rio de Janeiro 2015. www.bdtd.uerj.br:8443 /bitstream/1/14058/1 /TESE_FINAL_ROSA_MARIA _JARDIM_RODRIGUES_com %20alteracao%20%282%29.pdf (accessed 6 September 2021). Singh 2008
Singh S, Kumar V, Kumar S, Subbappa A. The effect of periodontal therapy on the improvement of glycaemic control in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. International Journal of Diabetes in Developing Countries 2008;28(2):38–44. [PMC free article: PMC2772010] [PubMed: 19902046]Sun 2011
Sun WL, Chen LL, Zhang SZ, Wu YM, Ren YZ, Qin GM. Inflammatory cytokines, adiponectin, insulin resistance and metabolic control after periodontal intervention in patients with type 2 diabetes and chronic periodontitis. Internal Medicine 2011;50(15):1569–74. [PubMed: 21804283]Telgi 2013
Telgi RL, Tandon V, Tangade PS, Tirth A, Kumar S, Yadav V. Efficacy of nonsurgical periodontal therapy on glycaemic control in type II diabetic patients: a randomized controlled clinical trial. Journal of Periodontal & Implant Science 2013;43(4):177–82. [DOI: 10.5051/jpis.2013.43.4.177] [PMC free article: PMC3769596] [PubMed: 24040570] [CrossRef]Tsobgny-Tsague 2018
Tsobgny-Tsague NF, Lontchi-Yimagou E, Nana AR N, Tankeu AT, Katte JC, Dehayem MY, et al EEects of nonsurgical periodontal treatment on glycated haemoglobin on type 2 diabetes patients (PARODIA 1 study): a randomized controlled trial in a subSaharan Africa population. BMC Oral Health 2018;18(1):28. [DOI: 10.1186/s12903-018-0479-5] [PMID: 2948254] [PMC free article: PMC5828384] [PubMed: 29482543] [CrossRef]Vergnes 2018
Vergnes JN, Arrivé E, Gourdy P, Hanaire H, Rigalleau V, Gin H et al Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial. Trials 2009;10:65. [PMC free article: PMC2727954] [PubMed: 19646281]- Vergnes JN, Canceill T, Vinel A, Laurencin-Dalicieux S, Maupas-Schwalm F, Blasco-Baqué V, et al The effects of periodontal treatment on diabetic patients: The DIAPERIO randomized controlled trial. Journal of Clinical Periodontology 2018;45(10):1150–63. [DOI: 10.1111/jcpe.13003] [PMID: 30136741] [PubMed: 30136741] [CrossRef]
Wang S 2017
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1.1.12.1. Effectiveness
References to studies included in the Cochrane review
Note: * Indicates the major publication for the study
1.1.12.2. Economic
1.1.12.3. Other references
Appendices
Appendix A. Review protocols
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Appendix B. Methods
The evidence presented in this review is based on the systematic review update conducted by Cochrane Oral Health (COH) as part of a collaboration between the NICE Guideline Development Team and Cochrane.
This review entitled “Treatment of periodontitis for glycaemic control in people with diabetes mellitus” (Simpson et al, 2015) was identified as a priority title during the Cochrane Oral Health 2020 prioritisation project. It was conducted using the methods described in detail in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et al. 2011).
Literature search, screening, and study selection
The literature search, eligibility screening and selection of studies were performed by the COH. Details of the search strategy are reported in Appendix C, included studies are presented in 1.1.4.1 Included studies, the PRISMA diagram in Appendix D and the evidence tables in Appendix E.
Evidence of effectiveness of interventions
Quality assessment
The COH assessed the risk of bias of individual RCTs in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 (Higgins 2011) against the following risk of bias criteria: random sequence generation; allocation concealment; blinding of outcome assessment; incomplete outcome data; selective outcome reporting; other potential biases. They also included the domains 'blinding of participants' and 'blinding of clinical operators' even though it is not possible to blind participants and personnel due to subgingival instrumentation / scaling and root planing being provided in one arm and not in the other. Each domain was assessed as being at low, high or unclear risk of bias. 'Unclear' indicates either lack of information or uncertainty over the potential for bias and this is presented in Appendix E.
The NICE Guideline Development Team further assessed and classified each individual study into one of three groups for directness, based on whether there were concerns about the relevance of the population, intervention, comparator and/or outcomes in the study and how directly these variables could address the specified review question. Studies were rated as follows:
- Direct – No important deviations from the protocol in population, intervention, comparator and/or outcomes.
- Partially indirect – Important deviations from the protocol in one of the following areas: population, intervention, comparator and/or outcomes.
- Indirect – Important deviations from the protocol in at least two of the following areas: population, intervention, comparator and/or outcomes.
Individual RCTs were also quality assessed based on the COH’s judgement for Risk of Bias. Each individual study was classified into one of the following three groups:
- Low risk of bias – The true effect size for the study is likely to be close to the estimated effect size.
- Moderate risk of bias – There is a possibility the true effect size for the study is substantially different to the estimated effect size.
- High risk of bias – It is likely the true effect size for the study is substantially different to the estimated effect size.
The NICE Guideline Development Team performed quality assessment of the Cochrane’s systematic review using the ROBIS tool, which classifies systematic reviews into one of the following three groups:
- High quality – It is unlikely that additional relevant and important data would be identified from primary studies compared to that reported in the review, and unlikely that any relevant and important studies have been missed by the review.
- Moderate quality – It is possible that additional relevant and important data would be identified from primary studies compared to that reported in the review, but unlikely that any relevant and important studies have been missed by the review.
- Low quality – It is possible that relevant and important studies have been missed by the review.
In addition, the Cochrane systematic review was also classified into one of three groups for its applicability as a source of data, based on how closely the review matched the specified review protocol in the guideline. The following applicability ratings were used:
- Fully applicable – The identified review fully covers the review protocol in the guideline.
- Partially applicable – The identified review fully covers a discrete subsection of the review protocol in the guideline.
- Not applicable – The identified review, despite including studies relevant to the review question, does not fully cover any discrete subsection of the review protocol in the guideline.
These assessments are presented in Appendix E.
Using the Cochrane systematic review as a source of data
The use of the Cochrane systematic review as a source of data was based on the criteria of its applicability and quality, as presented in the Table 9:
Table 9. Criteria for using systematic reviews as a source of data (PDF, 100K)
Data from this systematic review are presented in GRADE tables in the same way as if data had been extracted from primary studies.
Methods for combining intervention evidence
Meta-analyses of interventional data were conducted with reference to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et al. 2011). All the outcomes analysed were continuous. Pooled outcomes were expressed as mean differences with their associated 95% confidence intervals.
Fixed-effects models were the preferred choice to report the outcome data from the Cochrane review, but in situations where the assumption of a shared mean for fixed-effects model were clearly not met, even after appropriate pre-specified subgroup analyses were conducted, random-effects results are presented. Fixed-effects models were deemed to be inappropriate if one or both of the following conditions was met:
- Significant between study heterogeneity in methodology, population, intervention, or comparator was identified by the reviewer.
- The presence of significant statistical heterogeneity in the meta-analysis, defined as I2≥50%.
However, in cases where the results from individual pre-specified subgroup analyses are less heterogeneous (with I2 < 50%) the results from these subgroups were reported using fixed effects models. This may lead to situations where pooled results are reported from random-effects models and subgroup results are reported from fixed-effects models.
In situations where subgroup analyses were conducted, pooled results and results for the individual subgroups are reported when there was evidence of between group heterogeneity, defined as a statistically significant test for subgroup interactions (at the 95% confidence level). Where no such evidence was identified, only pooled results are presented.
In any meta-analyses where some (but not all) of the data came from studies at critical or high risk of bias, a sensitivity analysis was conducted, excluding those studies from the analysis.
Meta-analyses were performed in Cochrane Review Manager V5.3. Forest plots are presented in Appendix F.
Minimal clinically important differences (MIDs)
The Core Outcome Measures in Effectiveness Trials (COMET) database was searched to identify published minimal clinically important difference thresholds relevant to this guideline. Identified MIDs were assessed to ensure they had been developed and validated in a methodologically rigorous way, and were applicable to the populations, interventions and outcomes specified in this guideline.
MIDs found through this process and used to assess imprecision in the guideline are given in Table 10. For other continuous outcomes not specified in the table below, no MID was defined.
Table 10. Identified MIDs (PDF, 104K)
For continuous outcomes expressed as a mean difference where no other MID was available, an MID of 0.5 of the median standard deviations of the comparison group arms was used (Norman et al. 2003).
When decisions were made in situations where MIDs were not available, the ‘Evidence to Recommendations’ section of that review makes explicit the committee’s view of the expected clinical importance and relevance of the findings. In particular, this includes consideration of whether the whole effect of a treatment (which may be felt across multiple independent outcome domains) would be likely to be clinically meaningful, rather than simply whether each individual sub outcome might be meaningful in isolation.
GRADE for pairwise meta-analyses of interventional evidence
GRADE was used to assess the quality of evidence for the selected outcomes as specified in ‘Developing NICE guidelines: the manual (2018)’. As this review is based on Cochrane data from randomised controlled trials, the studies were initially rated as high quality. The quality of the evidence for each outcome was downgraded or not from this initial point, based on the criteria given in Table 11 below:
Table 11. Rationale for downgrading quality of evidence for intervention studies (PDF, 106K)
Summary of evidence is presented in section 1.1.6. This summarises the effect size, quality of evidence and interpretation of the evidence in relation to the significance of the data.
Evidence was also identified for which GRADE could not be applied due to the lack of data and/or its poor quality. This evidence has been summarised narratively in section 1.1.6. under the subheading Secondary outcomes.
The full GRADE tables can be found in Appendix G.
Publication bias
Publication bias was assessed for the diabetes outcome at 3-4 months by generating a funnel plot (Appendix E), which would indicate potential presence of reporting biases by testing for asymmetry, and via the Egger et al regression asymmetry test (Egger 1997).
Appendix C. Literature search strategies
Evidence review on effectiveness of periodontal treatment in improving diabetic control in adults with type 1 or type 2 diabetes.
Clinical search literature search strategy
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Appendix D. Effectiveness evidence study selection
Download PDF (113K)
Appendix E. Evidence tables for included studies
Download PDF (741K)
Risk of bias summary: Judgements about risk of bias domains for each included study
Download PDF (123K)
Risk of bias graph: Judgements about risk of bias domains presented as percentages across all included studies
Download PDF (103K)
Funnel plot of comparison: Periodontal therapy versus no active intervention/usual care at 3-4 months
Download PDF (107K)
Overall study risk of bias and applicability
Download PDF (190K)
ROBIS Risk of bias assessment summary of the Cochrane systematic review
Download PDF (143K)
Appendix F. Forest plots
These forests plots are based on data from the Cochrane draft review. In the GRADE tables, the subgroups marked with “ * ” are presented using fixed effects model in line with the NICE methods (Appendix B).
Effects of periodontal treatment versus usual care/no active intervention on HbA1c at 3-4 months
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Effects of periodontal treatment versus usual care / no active intervention on HbA1c at 6 months
Download PDF (132K)
Effects of periodontal treatment versus usual care / no active intervention on HbA1c at 12 months
Download PDF (132K)
Effects of periodontal treatment versus usual care / no active intervention on Clinical attachment loss (CAL) at 3-4 months
Download PDF (147K)
Effects of periodontal treatment versus usual care / no active intervention on Clinical attachment loss (CAL) at 6 months
Download PDF (147K)
Effects of periodontal treatment versus usual care / no active intervention on Probing pocket depth (PPD) at 3-4 months
Download PDF (130K)
Effects of periodontal treatment versus usual care / no active intervention on Probing pocket depth (PPD) at 6 months
Download PDF (132K)
Effects of periodontal treatment versus usual care / no active intervention on Probing pocket depth (PPD) at 12 months
Download PDF (132K)
Appendix G. GRADE tables for pairwise data
The GRADE tables were compiled by the NICE Guideline Development Team. Fixed and random-effects models were fitted, with the presented analysis dependent on the degree of heterogeneity in the assembled evidence (in line with NICE methods in Appendix B).
Effects of periodontal treatment versus usual care/no active intervention on HbA1c
Download PDF (195K)
Effects of periodontal treatment versus usual care/no active intervention on Clinical attachment loss (CAL)
Download PDF (203K)
Effects of periodontal treatment versus usual care/no active intervention on Probing pocket depth (PPD)
Download PDF (222K)
Appendix H. Economic evidence study selection
Download PDF (140K)
Appendix I. Economic evidence tables
Download PDF (142K)
Appendix J. Health economic model
Full details of the health economic model are shown in the economic model report.
Appendix K. Excluded studies
Clinical
A list of studies excluded from this review at full-text stage and the ongoing studies:
| Excluded studies (N=11) | Reasons for exclusion |
|---|---|
| Albrecht M, Banoczy J, Gyenes V, Ember G, Rigo O, Valkovics M, et al Treatment of gingivitis and periodontal disease with insadol in diabetics. Fogorvosi Szemle 1988;81:65–71 [PubMed: 3077359] | No HbA1c outcome reported. Study was not translated to English, but advice sought from a Hungarian speaker on the content |
|
* Botero JE, Yepes FL, Ochoa SP, Hincapie JP, Roldan N, Ospina CA, et al Effects of periodontal nonsurgical therapy plus azithromycin on glycemic control in patients with diabetes: a randomized clinical trial. Journal of Periodontal Research 2013;48(6):706–12. [PubMed: 23441920] Hincapié JP, Castrillón CA, Yepes FL, Roldan N, Becerra MA, Moreno SM, et al Microbiological effects of periodontal therapy plus azithromycin in patients with diabetes: results from a randomized clinical trial. Acta Odontológica Latinoamericana 2014;27(2):89–95. [PubMed: 25523961] | Poorly reported. Further data needed (particularly accurate HbA1c means/SDs, data re: statin use) from author to complete assessment. Attempts to contacted authors unsuccessful. Categorised as ‘awaiting classification’ in 2015 version of review |
|
* Chee HK, Lim LP, Tay F, Thai AC, Sum CF. Non-surgical periodontal therapy and serum lipid levels in patients with diabetes mellitus. Annals of the Royal Australasian College of Dental Surgeons 2006;18:46 [PubMed: 17668592] Chee HK, Lim LP, Tay F, Thai AC, Sum CF. Non-surgical periodontal treatment and lipid levels in diabetic patients. Annals of the Royal Australasian College of Dental Surgeons 2008;19:183. [PubMed: 22073478] | No indication whether patients had diagnosed periodontitis. Poorly reported. Insufficient data to complete assessment. Several attempts to contact authors for further details proved unsuccessful. Categorised as ‘awaiting classification’ in 2015 version of review |
|
ChiCTR2000030393. Study for the effect of periodontal basic treatment on the microflora of patients with chronic periodontitis and diabetes mellitus. www | Observational study |
| Elsadek MF, Ahmed BM, Alkhawtani DM, Zia Siddiqui A. A comparative clinical, microbiological and glycemic analysis of photodynamic therapy and Lactobacillus reuteri in the treatment of chronic periodontitis in type-2 diabetes mellitus patients. Photodiagnosis and Photodynamic Therapy 2020;29:101629. [PubMed: 31870899] | No mention of randomisation |
| Goel K, Pradhan S, Bhattarai MD. Effects of nonsurgical periodontal therapy in patients with moderately controlled type 2 diabetes mellitus and chronic periodontitis in Nepalese population. Clinical Cosmetic and Investigative Dentistry 2017;9:73–80. [PMC free article: PMC5522660] [PubMed: 28761379] | Not a relevant study design (quasi-randomised study) |
| Khader YS, Al Habashneh R, Al Malalheh M, Bataineh A. The eEect of full-mouth tooth extraction on glycemic control among patients with type 2 diabetes requiring extraction of all remaining teeth: a randomized clinical trial. Journal of Periodontal Research 2010;45(6):741–7. [PubMed: 20682017] | Non-periodontal intervention: full-mouth tooth extraction for patients whose remaining teeth were indicated for extraction |
|
Chandni R, Mammen J, Joseraj MG, Joseph R. Effect of nonsurgical periodontal therapy on insulin resistance in patients with type 2 diabetes mellitus and chronic periodontitis [abstract]. In: Conference: 75th Scientific Sessions of the American Diabetes Association Boston, MA United States. 2015. *Mammen J, Vadakkekuttical RJ, George JM, Kaziyarakath JA, Radhakrishnan CE. Effect of non-surgical periodontal therapy on insulin resistance in patients with type II diabetes mellitus and chronic periodontitis, as assessed by C-peptide and the Homeostasis Assessment Index. Journal of Investigative and Clinical Dentistry 2017;8(3). [PubMed: 27282797] | Not a relevant study design (no mention of randomisation) |
| NCT01255254. The efffect of oral hygiene and full mouth scaling on metabolic control in patients with Type II diabetes. clinicaltrials.gov/show/NCT01255254 (2010). | Correspondence with trial investigator (May 2013) indicated trial was abandoned due to recruitment issues |
| Peña Sisto M, Calzado de Silva MC, Suárez Avalo W, Peña Sisto L, González Heredia E. Effectiveness of the periodontal treatment in the metabolic control of patients with diabetes mellitus [Efectividad del tratamiento periodontal en el control metabólico de pacientes con diabetes mellitus]. Medisan 2018;22(3):1029–3019. | Not a relevant study design (quasi-randomised study) |
|
*Phetnin N, Vichayanrat T, Anunmana C. Effectiveness of the Diabetic and Oral Care Program for Senior in Older Patients with Diabetes in Muang District, Nakhon Ratchasima Province. In: RSU International Research Conference 2020.
TCTR20200423005. Effectiveness of the Diabetic and Oral Care Program for Senior in Thai Older People with Type 2 Diabetes Mellitus: A randomized control trial. trialsearch | Not a relevant study design (quasi- randomised study) |
| Ongoing studies (N=4) |
|---|
|
ACTRN12605000260628. Assessment of diabetes after periodontal treatment. www |
| NCT01291875. Periodontal treatment and metabolic control in Type 2 diabetic patients. clinicaltrials.gov/ct2/show/NCT01291875 (first received 9 February 2011). |
| NCT01901926. Impact of non-surgical periodontal treatment on glycemic control in Type II diabetics. clinicaltrials.gov/ct2/show/NCT01901926 (first received 17 July 2013). |
|
U1111-1124-3635. Influence of periodontal treatment in periodontitis and diabetes control. www |
- *
Major publication for the study; RCT - randomised controlled trial; SRP - scaling and root planing; SD - standard deviation
Health Economics
| Excluded studies (N=2) | Reasons for exclusion |
|---|---|
| Choi, Sung Eun; Sima, Corneliu; Pandya, Ankur; Impact of Treating Oral Disease on Preventing Vascular Diseases: A Model-Based Cost-effectiveness Analysis of Periodontal Treatment Among Patients With Type 2 Diabetes.; Diabetes care; 2020; vol. 43 (no. 3); 563–571 [PubMed: 31882408] | Incorrect population, included some patients without diabetes and is a US based study, not representative of UK population. |
| Canadian Agency for Drugs and Technologies in, Health; Treatment of periodontal disease in patients with diabetes: a review of clinical and cost-effectiveness; 2010, Canadian Agency for Drugs and Technologies in Health (CADTH) | Systematic review, one study was identified from this paper which was screened out at the title and abstract stage. |
Tables
Table 1Summary of the protocol
| PICO Table | |
|---|---|
| Population | Adults (18+) with type 1 or type 2 diabetes and periodontitis |
| Interventions |
A non-surgical periodontal treatment such as subgingival instrumentation also known as scaling and root planing (SRP), which may include one or more of the following:
Studies combining periodontal treatment with usual care or with antimicrobial therapy (antibacterial and antibiotics) will be grouped for the purpose of the analysis. |
| Comparator |
|
| Outcomes |
Primary outcomes
Secondary outcomes
All outcomes reported at least 90 days following the intervention and grouped at 3 months, 6 months, 12 months |
| Study type |
|
Table 2Effects of periodontal treatment versus usual care/no active intervention on HbA1c
| Outcome: HbA1c (%) | No. of studies | Sample size | Effect estimate MD [95% CI] | MID | Quality | Interpretation of effect |
|---|---|---|---|---|---|---|
| Periodontal treatment vs usual care/no active intervention at 3-4 months | 30 | 2443 | −0.43 [−0.59, −0.28] | +/− 0.50 | Very low | Effect (favouring periodontal treatment) |
| Periodontal treatment vs usual care/no active intervention at 6 months | 12 | 1457 | −0.30 [−0.52, −0.08] | +/− 0.50 | Very low | Effect (favouring periodontal treatment) |
| Periodontal treatment vs usual care/no active intervention at 12 months | 1 | 264 | −0.50 [−0.55, −0.45] * | +/− 0.50 | Moderate | Effect (favouring periodontal treatment) |
- *
Subgroups reported using fixed effect model due to I2<50% (as per NICE methods, Appendix B)
Table 3Effects of periodontal treatment versus usual care/no active intervention on clinical attachment loss (CAL)
| Outcome: CAL (mm) | No. of studies | Sample size | Effect estimate MD [95% CI] | MIDs | Quality | Interpretation of effect |
|---|---|---|---|---|---|---|
| Periodontal treatment vs usual care/no active intervention at 3-4 months | 18 | 1606 | −0.48 [−0.65, −0.31] | +/− 0.41 | Very low | Effect (favouring periodontal treatment) |
| Periodontal treatment vs usual care/no active intervention at 6 months | 5 | 789 | −0.52 [−0.77, −0.26] | +/− 0.32 | Very low | Effect (favouring periodontal treatment) |
| SRP vs usual care/no active intervention at 6 months | 4 | 329 | −0.66 [−0.80, −0.53] * | +/− 0.41 | Moderate | Effect (favouring periodontal treatment) |
| SPR + mouth rinse vs usual care/no active intervention at 6 months | 1 | 460 | −0.25 [−0.36, −0.14] * | +/− 0.15 | Moderate | Effect (favouring periodontal treatment) |
- *
Subgroups reported using fixed effect model due to I2<50% (as per NICE methods, Appendix B)
Table 4Effects of periodontal treatment versus usual care/no active intervention on probing pocket depth (PPD)
| Outcome PPD (mm) | No. of studies | Sample size | Effect estimate MD [95% CI] | MIDs | Quality | Interpretation of effect |
|---|---|---|---|---|---|---|
| Periodontal treatment vs usual care/no active intervention at 3-4 months | 21 | 1775 | −0.56 [−0.72, −0.40] | +/− 0.31 | Very low | Effect (favouring periodontal treatment) |
| SRP vs usual care/no active intervention 3-4 months | 12 | 691 | −0.48 [−0.70, −0.26] | +/− 0.28 | Very low | Effect (favouring periodontal treatment) |
| SPR + local/ systemic antimicrobials vs usual care/no active intervention at 3-4 months | 9 | 532 | −0.76 [−1.09, −0.43] | +/− 0.30 | Very low | Effect (favouring periodontal treatment) |
| SPR + mouth rinse vs usual care/no active intervention at 3-4 months | 3 | 532 | −0.30 [−0.41, −0.20] * | +/− 0.35 | Moderate | Effect (favouring periodontal treatment) |
| Periodontal treatment vs usual care/no active intervention at 6 months | 8 | 1181 | −0.50 [−0.70, −0.29] | +/− 0.32 | Very low | Effect (favouring periodontal treatment) |
| Periodontal treatment vs usual care/no active intervention at 12 months | 1 | 264 | −0.90 [−1.18, −0.62] * | +/− 0.57 | Moderate | Effect (favouring periodontal treatment) |
- *
Subgroups reported using fixed effect model due to I2<50% (as per NICE methods, Appendix B)
Table 5Effects of maintenance treatment versus no maintenance treatment on HbA1c at 6 months
| HbA1c measured at 6 months | ||||
|---|---|---|---|---|
| Maintenance | Number of studies | Effect size MD [95% CI] | Heterogeneity P-value; I2 | P-value for subgroup comparison |
| Maintenance | 8 | −0.23 [−0.45, −0.01] | <1×10−5; 82% | |
| No maintenance | 3 | −0.06 [−0.60, 0.47] | 0.30; 16% | |
| Overall | 10* | <1×10−5; 76% | 0.58 | |
- *
Two arms from one study (Chen 2012) included in both subgroups
Table 6Summary of economic evidence
| Study | Study type | Setting | Interventions | Population | Methods of analysis | Base-case results | Sensitivity analyses | Additional comments |
|---|---|---|---|---|---|---|---|---|
| Solowiej-Wedderburn et al 2017 | Cost utility analysis using simulation model DiabForecaster McEwan et al 2006 to estimate the impact of reductions in HbA1c on lifetime costs of diabetes management | UK Setting. Provider perspective: includes costs to health care and dental care providers |
Non-surgical periodontal therapy: Scaling and root planning provided by the dentist and lifetime maintenance therapy is commenced by the patient, with dental retreatment as necessary. Periodontal therapy: Two 60-minute sessions delivered by a practitioner with experience of periodontal treatment Followed by maintenance of: 30-minute hygienist sessions every 3 months and follow-up of periodontal therapy of one 60-minute session every 3 years No treatment: Regular dental care only which comprises of routine scale and polish | People with periodontitis newly diagnosed with T2DM not previously receiving regular periodontal maintenance. The base case analysis assumes a 58-year-old man with a baseline HbA1c level of 7-7.9%. |
Change in HbA1c sourced from previous Cochrane review by Simpson et al., 2015. Effectiveness separated by patient compliance, model assumed 30% patients compliant with maintenance treatment based on rates reported in the literature of 11-70% (Fardal, Johannessen,& Linden, 2003; Pretzl et al., 2009; Ramseier et al., 2014). 87% of compliant patients assumed to respond to treatment (Lorentz, Miranda Cota, Cortelli, Vargas, & Costa, 2009) Remaining 13% assumed to incur full cost of treatment and maintenance without benefit Non-compliant patients assumed to only incur the costs of the initial treatment and tooth loss repair and assumed to have no benefit of treatment Time horizon: Lifetime Discount rate: 3.5% | £28,000 per QALY for a man aged 58 with glycated haemoglobin of 7-7.9% |
Deterministic: impact of periodontal therapy on HbA1c, percentage of compliance and response were the main drivers of cost - effectiveness results Probabilistic: not completed |
Source of funding: Unfunded Limitations identified by the authors: 1) Large uncertainty around the decrease in HbA1c attributable to periodontal treatment; 2) Results dependent on short term gains in HbA1c if treatment are maintained; 3) insufficient long-term data. Authors’ conclusions: Periodontal therapy may be cost-effective for patients with type 2 diabetes assuming improvements in HbA1c are maintained |
Table 7Type 1 base-case deterministic cost-utility results
| Treatments | Absolute | Incremental | |||
|---|---|---|---|---|---|
| Costs (£) | QALYs | Costs (£) | QALYs | ICER (vs usual care) | |
| Usual care | £44,048 | 12.741 | |||
| Periodontal treatment | £42,977 | 12.796 | −£1,070 | 0.055 | Dominates |
Table 8Type 2 base-case deterministic cost-utility results
| Treatments | Absolute | Incremental | |||
|---|---|---|---|---|---|
| Costs (£) | QALYs | Costs (£) | QALYs | ICER (vs usual care) | |
| Usual care | £10,840 | 7.895 | |||
| Periodontal treatment | £11,087 | 7.917 | £247 | 0.022 | £11,375* |
- *
The costs and QALYs in the table are rounded and the ICER is calculated using the exact values, therefore the ICER in the table is slightly different
Final version
Evidence reviews underpinning recommendations 1.15.1 to 1.15.4 (NG17) and recommendations 1.7.1 to 1.7.4 (NG28) and research recommendations in the NICE guidelines
These evidence reviews were developed by the Guideline Development Team
Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.