What is the effect of population-level screening of asymptomatic adults for type 2 diabetes mellitus or intermediate hyperglycaemia on health outcomes: summary

iWHO HEALTH EVIDENCE NETWORK SYNTHESIS REPORT, 79 What is the effect of population-level screening of asymptomatic adults for type 2 diabetes mellitus or intermediate hyperglycaemia on health outcomes? Summary Chris Stinton | Alice Mansbridge | Hannah Williams | Deshani Herath | Janette Parr | Amy Grove | Laura Kudrna | Oxana Rotar | Samantha A Johnson | Oyinlola Oyebode | Lena Al-Khudairy | Sian Taylor-Phillips The Health Evidence Network The Health Evidence Network (HEN) is an information service for public health decision-makers in the WHO European Region, in action since 2003 and initiated and coordinated by the WHO Regional Office for Europe under the umbrella of the WHO European Health Information Initiative (a multipartner network coordinating all health information activities in the WHO European Region). HEN supports public health decision-makers to use the best available evidence in their own decision- making and aims to ensure links between evidence, health policies and improvements in public health. The HEN synthesis report series provides summaries of what is known about the policy issue, the gaps in the evidence and the areas of debate. Based on the synthesized evidence, HEN proposes policy considerations, not recommendations, for policy-makers to formulate their own recommendations and policies within their national context. The Noncommunicable Diseases Management unit The Noncommunicable Diseases Management unit of the WHO Regional Office for Europe works to close the gap between the eastern and western Member States of the WHO European Region in cancer, cardiovascular diseases, chronic respiratory diseases, diabetes and oral diseases. The Noncommunicable Diseases Management unit provides strategic direction, technical assistance, disease-specific advice and tailored support to Member States to build country capacity. By combining evidence and expertise, it supports countries in the implementation of priority interventions across the care continuum to, for example, build quality-assured screening programmes, increase compliance with care standards and improve service delivery models that advance objectives related to health system strengthening, people-centred health care and the achievement of universal health coverage. WHO Health Evidence Network synthesis report, 79 What is the effect of population-level screening of asymptomatic adults for type 2 diabetes mellitus or intermediate hyperglycaemia on health outcomes? Summary Chris Stinton | Alice Mansbridge | Hannah Williams | Deshani Herath | Janette Parr | Amy Grove | Laura Kudrna | Oxana Rotar | Samantha A Johnson | Oyinlola Oyebode | Lena Al-Khudairy | Sian Taylor-Phillips Abstract Diabetes mellitus is one of the world's fastest growing chronic conditions. It is associated with heart disease, eye and kidney problems, and premature death. Intermediate hyperglycaemia, a state in which blood glucose levels are above the normal range but below the threshold for diabetes, is associated with an increased risk for type 2 diabetes (T2DM), obesity, cardiovascular diseases and mortality. The review assessed whether population-level screening for intermediate hyperglycaemia and T2DM can improve health outcomes. A single, underpowered, biased study found no benefit of population-level screening for T2DM to reduce morbidity or mortality. No studies reported whether treatment after screen detection improved health outcomes compared with either no treatment or treatment after later symptomatic detection. One underpowered study found no significant difference in health outcomes between more- and less-intensive treatment after screen detection. In summary, there is currently no evidence that screening for T2DM or IHG reduces morbidity or mortality. Keywords REVIEW, MASS SCREENING, DIABETES MELLITUS, POPULATION, RANDOMIZED CONTROL TRIAL Document number: WHO/EURO:2024-10169-49941-75068 © World Health Organization 2024 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC- SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. The named authors alone are responsible for the views expressed in this publication. 1SUMMARY The issue Diabetes mellitus (referred to as diabetes in this report) is a chronic health condition that affects one in 11 adults in the WHO European Region. It is associated with morbidities such as heart disease, eye and kidney problems, and premature death. In 2021 1.1 million deaths were attributed to diabetes-related complications in the 59 countries and territories of the International Diabetes Federation (IDF) Europe Region. In this Region, an estimated one third of people with diabetes are undiagnosed. Lesser degrees of hyperglycaemia that do not reach the threshold for diagnosis of diabetes mellitus (referred to as intermediate hyperglycaemia) can be associated with an increased risk of developing diabetes and cardiovascular diseases. The high prevalence and potential long-term health consequences of these conditions has led to consideration of the possible health benefits of screening for them. Population-level screening is a public health strategy to reduce the burden of disease in society by identifying and managing preclinical disease or the risk factors of disease among asymptomatic people. However, screening is associated with both benefits and harms. There is uncertainty about whether screening for diabetes (or intermediate hyperglycaemia) leads to improvements in health outcomes. The synthesis question The overall objective of this report is to evaluate the evidence on the benefits and harms of population-level screening for type 2 diabetes mellitus (T2DM) and intermediate hyperglycaemia. Types of evidence This report builds on a broad review published in 2021 that covered questions related to screening, interventions and the natural history of T2DM and intermediate hyperglycaemia. Six questions from that review were updated and expanded using a rapid review approach complemented by a grey literature search. Searches in English and Russian were conducted between June and September 2022 for randomized controlled trials (RCTs) of screening for T2DM and intermediate hyperglycaemia. WHAT IS THE EFFECT OF POPULATION-LEVEL SCREENING OF ASYMPTOMATIC ADULTS FOR TYPE 2 DIABETES MELLITUS OR INTERMEDIATE HYPERGLYCAEMIA ON HEALTH OUTCOMES? WHO HEALTH EVIDENCE NETWORK SYNTHESIS REPORT 2 Results Together, the present and previous review identified a total of 19 papers reporting on seven RCTs: one RCT provided direct evidence on screening for T2DM and six provided indirect evidence (i.e. assessed parts of a screening pathway in order to estimate what a direct trial of the whole screening pathway might show) through assessment of interventions for people with screen-detected or recently diagnosed T2DM. Four RCTs reported data on harms. There is no direct evidence, or linked chain of indirect evidence, that demonstrates that screening for T2DM improves outcomes. One RCT found no benefit of offering screening, but it was underpowered and had a high risk of bias. No studies reported whether treatment after screen detection improved health outcomes compared with either no treatment or treatment after later symptomatic detection. One underpowered study found no significant difference in health outcomes between more- and less-intensive treatment after screen detection. In general, studies of people with recently diagnosed T2DM found no difference between intervention and control groups for all-cause mortality, amputation, myocardial infarction, renal failure, stroke or visual impairment, although follow-up times were likely to be insufficient. There was evidence in favour of intervention for people with recently detected T2DM and hypertension (tight blood pressure control with captopril or atenolol was associated with reductions in stroke and visual deterioration) and for people with recently detected T2DM who were overweight (i.e. metformin treatment was associated with a reduction in all-cause mortality). No differences in harms between intervention and control groups were reported for people with screen-detected or recently diagnosed T2DM. None of the included RCTs reported detecting people with intermediate hyperglycaemia. Caution is warranted in drawing firm conclusions on the potential benefits and harms of screening for T2DM because the evidence base is small, study populations are not generalizable to screening populations and, in general, studies were not adequately powered to detect differences in longer-term health outcomes between groups. Policy considerations Based on the review findings, considerations for Member States of the WHO European Region are: • to avoid initiating new population-level screening programmes for T2DM or intermediate hyperglycaemia; 3• to review the rationale for existing systematic population-level screening programmes for T2DM or intermediate hyperglycaemia, and consider stopping them in favour of exploring alternative approaches to reducing the burden of T2DM and its complications; and • if new or expanded screening is initiated, to do so in a manner that incorporates research so that the impact on health outcomes and costs on health systems can be measured. Document number: WHO/EURO:2024-10169-49941-75068 World Health Organization Regional Office for Europe UN City, Marmorvej 51, DK-2100 Copenhagen Ø, Denmark Tel.: +45 45 33 70 00 Fax: +45 45 33 70 01 Email: eurocontact@who.int Website: www.who.int/europe