NIHR Signal Diet and exercise programmes can prevent diabetes in high-risk individuals

Published on 27 February 2018

Lifestyle changes can reduce the risk of diabetes by about 40% and overall prevents about four high-risk individuals in 100 developing type 2 diabetes each year. The risk remained low for an average of about seven years after the intervention, but effects did decline over time. Medications including the weight-loss drug orlistat and diabetes drug metformin also reduced risk. But in contrast, there was no evidence of sustained effect after stopping treatment.

Type 2 diabetes accounts for a large proportion of the chronic disease burden globally. Past research demonstrated that interventions leading to weight loss could prevent the condition.     

This review combines international data from over 40 trials looking at the long-term impact of medication and lifestyle modification compared with control.

Findings support current NICE recommendations. Lifestyle change programmes, targeting both diet and exercise, are promoted as a central component of care to reduce the risk of type 2 diabetes in high-risk individuals.   

Share your views on the research.

Why was this study needed?

In England, around a third of adults are thought to have “pre-diabetes” where their blood sugar is raised but below the threshold for diabetes. Between 5 and 10% are estimated to convert to type 2 diabetes every year.

Six in every 100 UK adults have type 2 diabetes. The condition can lead to adult-onset blindness, kidney failure, surgical amputation, and an increased risk of cardiovascular illness and death. Around 10% of the total NHS budget is spent managing the disease and its complications.  

Previous studies have shown that diet, physical activity and medical interventions (such as the weight-loss drugs orlistat) can be cost-effective for preventing diabetes in various settings and populations. However, it is unclear which preventive strategies, and at what dose or frequency, is most effective for giving a sustained benefit.

This systematic review compares the long-term impact of different prevention strategies to better guide national diabetes prevention programmes.

What did this study do?

The review identified 53 randomised controlled trials assessing prevention strategies in 49,029 adults with prediabetes. Studies of bariatric surgery, alternative therapies and including people with metabolic syndrome were excluded. 

Results from 43 studies were pooled in meta-analysis. Average participant age was 57 years, and body mass index was borderline obese (BMI 30.8). Nineteen studies evaluated single or multiple medications, 19 tested lifestyle modifications, and five tested both lifestyle modifications and medications. Follow-up times ranged from six months to six years in 40 studies, with three studies assessing outcomes at 10-20 years.

Studies were published from 1990 to 2015 and included European, North American and Asian populations. Around 80% were judged to be moderate-to-high quality. However, study results were highly variable, possibly owing to differences in interventions, the classifications of diabetes and prediabetes used or the study setting.

What did it find?

  • At the end of treatment (average 2.6 years) lifestyle modification reduced risk of diabetes by about 40% (relative risk [RR], 0.61, 95% confidence interval [CI] 0.54 to 0.68; 19 studies). Diabetes developed in around seven per 100 people per year following combined diet and physical activity strategies compared with 11 per 100 controls. Overall 25 people would be needed to be treated to prevent one case of diabetes.
  • Medication also reduced risk of diabetes at the end of the treatment period (average 3.1 years). Weight loss drugs like orlistat gave the highest overall risk reduction (RR 0.37, 95% CI 0.22 to 0.62), followed by certain diabetes drugs including metformin (RR 0.47, 95% CI 0.32 to 0.68). An overall risk reduction of 36% was found across all medication studies, though this included three lifestyle-plus-medication studies (RR 0.64, 95% CI 0.54 to 0.76; 21 studies). There were five cases of diabetes per 100 people taking medication per year compared with nine per 100 controls. Overall 25 people would need treatment to prevent one case of diabetes.
  • Four studies considered the effect of lifestyle modification at later follow-up (average 7.2 years). Three were diet and physical activity interventions, and one trial looked at a reduced-fat diet alone. Overall the risk of diabetes was 28% lower at follow-up compared to controls (RR 0.72, 95% CI 0.60 to 0.86). This had decreased from a 45% risk reduction at the end of active treatment in the same studies.
  • Six studies found no sustained effect of various medicines at longer follow-up ranging from two to 52 weeks after treatment completion (RR 0.95, 95% CI 0.79 to 1.14).

What does current guidance say on this issue?

NICE guidelines on prevention of type 2 diabetes recommend that risk assessment is carried out in adults aged over 40 years (younger adults from certain minority ethnic groups) with conditions that increase their risk of type 2 diabetes. Those eligible can also be assessed through the NHS Health Check programme. A person is considered high-risk of diabetes if they have fasting blood glucose of 5.5-6.9 mmol/l or HbA1c of 42-47 mmol/mol.  

NICE recommends lifestyle-modification programmes for people at high risk. Metformin is recommended only if blood glucose control has deteriorated despite lifestyle change, or if a person is unable to participate in such programmes, particularly if their BMI is above 35kg/m2. Similarly, orlistat may be considered if BMI is above 28. No other drug therapies are recommended.

What are the implications?

The findings strengthen NICE recommendations to consider lifestyle change first-line in people at high risk of type-2 diabetes. This is in line with the new Diabetes Prevention Programme launched in England in 2016.

There is little evidence to show that medication effects are sustained once drug treatment stops. The risk-reducing impact of lifestyle modification also lessened about three years following active therapy. Future research could explore whether maintenance interventions are required to prolong effects.

Citation and Funding

Haw JS, Galaviz KI, Straus AN, et al. Long-term sustainability of diabetes prevention approaches: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2017;177(12):1808-17.

Bibliography

Li R, Qu S, Zhang P, et al. Economic evaluation of combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the community preventive services task force. Ann Intern Med. 2015;163(6):452-60.

Mainous AG, Tanner RJ, Baker R, et al. Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study. BMJ Open. 2014;4(6).

NHS England. NHS Diabetes Prevention Programme (NHS DPP). London: NHS England.

NICE. Type 2 diabetes: prevention in people at high risk. PH38. London: National Institute for Health and Care Excellence; 2012.

Kanavos P, Aardweg S Van Den, Schurer W. Diabetes expenditure, burden of disease and management in 5 EU countries. London: LSE Health, London School of Economics; 2012.

Sutton M, Sanders C, Reeves D, et al. Evaluating the NHS Diabetes Prevention Programme (NHS DPP): the DIPLOMA research programme (Diabetes Prevention Long term Multimethod Assessment). Health Services and Delivery Research programme, project number 16/48/07. Southampton: National Institute for Health Research; 2017.

Tabák AG, Herder C, Rathmann W, et al. Prediabetes: a high-risk state for diabetes development. Lancet. 2012;379(9833):2279-90.

World Health Organization. Global status report on noncommunicable diseases 2010. Geneva: World Health Organization; 2011.

Why was this study needed?

In England, around a third of adults are thought to have “pre-diabetes” where their blood sugar is raised but below the threshold for diabetes. Between 5 and 10% are estimated to convert to type 2 diabetes every year.

Six in every 100 UK adults have type 2 diabetes. The condition can lead to adult-onset blindness, kidney failure, surgical amputation, and an increased risk of cardiovascular illness and death. Around 10% of the total NHS budget is spent managing the disease and its complications.  

Previous studies have shown that diet, physical activity and medical interventions (such as the weight-loss drugs orlistat) can be cost-effective for preventing diabetes in various settings and populations. However, it is unclear which preventive strategies, and at what dose or frequency, is most effective for giving a sustained benefit.

This systematic review compares the long-term impact of different prevention strategies to better guide national diabetes prevention programmes.

What did this study do?

The review identified 53 randomised controlled trials assessing prevention strategies in 49,029 adults with prediabetes. Studies of bariatric surgery, alternative therapies and including people with metabolic syndrome were excluded. 

Results from 43 studies were pooled in meta-analysis. Average participant age was 57 years, and body mass index was borderline obese (BMI 30.8). Nineteen studies evaluated single or multiple medications, 19 tested lifestyle modifications, and five tested both lifestyle modifications and medications. Follow-up times ranged from six months to six years in 40 studies, with three studies assessing outcomes at 10-20 years.

Studies were published from 1990 to 2015 and included European, North American and Asian populations. Around 80% were judged to be moderate-to-high quality. However, study results were highly variable, possibly owing to differences in interventions, the classifications of diabetes and prediabetes used or the study setting.

What did it find?

  • At the end of treatment (average 2.6 years) lifestyle modification reduced risk of diabetes by about 40% (relative risk [RR], 0.61, 95% confidence interval [CI] 0.54 to 0.68; 19 studies). Diabetes developed in around seven per 100 people per year following combined diet and physical activity strategies compared with 11 per 100 controls. Overall 25 people would be needed to be treated to prevent one case of diabetes.
  • Medication also reduced risk of diabetes at the end of the treatment period (average 3.1 years). Weight loss drugs like orlistat gave the highest overall risk reduction (RR 0.37, 95% CI 0.22 to 0.62), followed by certain diabetes drugs including metformin (RR 0.47, 95% CI 0.32 to 0.68). An overall risk reduction of 36% was found across all medication studies, though this included three lifestyle-plus-medication studies (RR 0.64, 95% CI 0.54 to 0.76; 21 studies). There were five cases of diabetes per 100 people taking medication per year compared with nine per 100 controls. Overall 25 people would need treatment to prevent one case of diabetes.
  • Four studies considered the effect of lifestyle modification at later follow-up (average 7.2 years). Three were diet and physical activity interventions, and one trial looked at a reduced-fat diet alone. Overall the risk of diabetes was 28% lower at follow-up compared to controls (RR 0.72, 95% CI 0.60 to 0.86). This had decreased from a 45% risk reduction at the end of active treatment in the same studies.
  • Six studies found no sustained effect of various medicines at longer follow-up ranging from two to 52 weeks after treatment completion (RR 0.95, 95% CI 0.79 to 1.14).

What does current guidance say on this issue?

NICE guidelines on prevention of type 2 diabetes recommend that risk assessment is carried out in adults aged over 40 years (younger adults from certain minority ethnic groups) with conditions that increase their risk of type 2 diabetes. Those eligible can also be assessed through the NHS Health Check programme. A person is considered high-risk of diabetes if they have fasting blood glucose of 5.5-6.9 mmol/l or HbA1c of 42-47 mmol/mol.  

NICE recommends lifestyle-modification programmes for people at high risk. Metformin is recommended only if blood glucose control has deteriorated despite lifestyle change, or if a person is unable to participate in such programmes, particularly if their BMI is above 35kg/m2. Similarly, orlistat may be considered if BMI is above 28. No other drug therapies are recommended.

What are the implications?

The findings strengthen NICE recommendations to consider lifestyle change first-line in people at high risk of type-2 diabetes. This is in line with the new Diabetes Prevention Programme launched in England in 2016.

There is little evidence to show that medication effects are sustained once drug treatment stops. The risk-reducing impact of lifestyle modification also lessened about three years following active therapy. Future research could explore whether maintenance interventions are required to prolong effects.

Citation and Funding

Haw JS, Galaviz KI, Straus AN, et al. Long-term sustainability of diabetes prevention approaches: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2017;177(12):1808-17.

Bibliography

Li R, Qu S, Zhang P, et al. Economic evaluation of combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the community preventive services task force. Ann Intern Med. 2015;163(6):452-60.

Mainous AG, Tanner RJ, Baker R, et al. Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study. BMJ Open. 2014;4(6).

NHS England. NHS Diabetes Prevention Programme (NHS DPP). London: NHS England.

NICE. Type 2 diabetes: prevention in people at high risk. PH38. London: National Institute for Health and Care Excellence; 2012.

Kanavos P, Aardweg S Van Den, Schurer W. Diabetes expenditure, burden of disease and management in 5 EU countries. London: LSE Health, London School of Economics; 2012.

Sutton M, Sanders C, Reeves D, et al. Evaluating the NHS Diabetes Prevention Programme (NHS DPP): the DIPLOMA research programme (Diabetes Prevention Long term Multimethod Assessment). Health Services and Delivery Research programme, project number 16/48/07. Southampton: National Institute for Health Research; 2017.

Tabák AG, Herder C, Rathmann W, et al. Prediabetes: a high-risk state for diabetes development. Lancet. 2012;379(9833):2279-90.

World Health Organization. Global status report on noncommunicable diseases 2010. Geneva: World Health Organization; 2011.

Long-term Sustainability of Diabetes Prevention Approaches: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Published on 9 November 2017

Haw, J. S.,Galaviz, K. I.,Straus, A. N.,Kowalski, A. J.,Magee, M. J.,Weber, M. B.,Wei, J.,Narayan, K. M. V.,Ali, M. K.

JAMA Intern Med , 2017

Importance: Diabetes prevention is imperative to slow worldwide growth of diabetes-related morbidity and mortality. Yet the long-term efficacy of prevention strategies remains unknown. Objective: To estimate aggregate long-term effects of different diabetes prevention strategies on diabetes incidence. Data Sources: Systematic searches of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases. The initial search was conducted on January 14, 2014, and was updated on February 20, 2015. Search terms included prediabetes, primary prevention, and risk reduction. Study Selection: Eligible randomized clinical trials evaluated lifestyle modification (LSM) and medication interventions (>6 months) for diabetes prevention in adults (age >/=18 years) at risk for diabetes, reporting between-group differences in diabetes incidence, published between January 1, 1990, and January 1, 2015. Studies testing alternative therapies and bariatric surgery, as well as those involving participants with gestational diabetes, type 1 or 2 diabetes, and metabolic syndrome, were excluded. Data Extraction and Synthesis: Reviewers extracted the number of diabetes cases at the end of active intervention in treatment and control groups. Random-effects meta-analyses were used to obtain pooled relative risks (RRs), and reported incidence rates were used to compute pooled risk differences (RDs). Main Outcomes and Measures: The main outcome was aggregate RRs of diabetes in treatment vs control participants. Treatment subtypes (ie, LSM components, medication classes) were stratified. To estimate sustainability, post-washout and follow-up RRs for medications and LSM interventions, respectively, were examined. Results: Forty-three studies were included and pooled in meta-analysis (49029 participants; mean [SD] age, 57.3 [8.7] years; 48.0% [n = 23549] men): 19 tested medications; 19 evaluated LSM, and 5 tested combined medications and LSM. At the end of the active intervention (range, 0.5-6.3 years), LSM was associated with an RR reduction of 39% (RR, 0.61; 95% CI, 0.54-0.68), and medications were associated with an RR reduction of 36% (RR, 0.64; 95% CI, 0.54-0.76). The observed RD for LSM and medication studies was 4.0 (95% CI, 1.8-6.3) cases per 100 person-years or a number-needed-to-treat of 25. At the end of the washout or follow-up periods, LSM studies (mean follow-up, 7.2 years; range, 5.7-9.4 years) achieved an RR reduction of 28% (RR, 0.72; 95% CI, 0.60-0.86); medication studies (mean follow-up, 17 weeks; range, 2-52 weeks) showed no sustained RR reduction (RR, 0.95; 95% CI, 0.79-1.14). Conclusions and Relevance: In adults at risk for diabetes, LSM and medications (weight loss and insulin-sensitizing agents) successfully reduced diabetes incidence. Medication effects were short lived. The LSM interventions were sustained for several years; however, their effects declined with time, suggesting that interventions to preserve effects are needed.

Expert commentary

The message from this review is clear; we need lifetime dietary change, but not a return to the era of low weight due to poverty. Rather, we should learn from other epidemiological clues.

In developed countries, higher educational attainment and higher income are associated with lower BMI – “poor is fat and rich is thin”, suggesting that increased awareness can buck the trend of increasing income increasing weight. Culture also has a strong part to play, with obesity rates in France being around half of those in the UK.

Sending the right dietary messages seems a good place to start: time to put the chocolate behind the counter next to the cigarettes.

Colin Dayan, Professor of Clinical Diabetes and Metabolism, Cardiff University School of Medicine

Expert commentary

Preventing Type 2 diabetes through lifestyle changes and/ or medication is critical given the growing number of people at increased risk of developing the condition. There are 11.9 million people currently in the UK alone who may develop type 2 diabetes if they don’t take preventative action.

We need to better understand the differences in how people respond to changes in their diet and physical activity and different types of medications. We can then develop effective, targeted approaches that offer people the real long-term benefits of living without this serious condition.

Dr Elizabeth Robertson, Director of Research, Diabetes UK