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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.
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.
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