How did we identify and evaluate the evidence?
We searched the medical literature to review the evidence on the effects of pharmacological (drug), behavioural (behaviour change) and organisational (delivery of health care) interventions for the prevention of type 2 diabetes among people with mental disorders in low- and middle-income countries (LMICs). Type 2 diabetes is a serious health condition that may develop when the body can no longer properly use a hormone called insulin. There are many reasons why a person may develop type 2 diabetes, including being overweight, having high blood pressure, not getting enough exercise, having a family history of the disease, and several other possible risk factors.
We included randomized controlled trials (RCTs) published up to our search date, 20 February 2020.
Why is this important?
People with mental health conditions such as schizophrenia, bipolar disorder, and major depressive disorder are more likely to develop type 2 diabetes than the general population. Many people suffering from mental health conditions, who are at an increased risk of developing diabetes, live in LMICs. Treating diabetes in this population poses challenges to healthcare systems. Preventing the development of diabetes is therefore important to people with mental health conditions and to healthcare systems in LMICs.
What did we find?
Among adults with mental health conditions, we identified only one study that assessed our primary outcome, prevention of type 2 diabetes. This hospital-based study with 150 participants (99 participants with schizophrenia) found low-certainty evidence of no difference in risk between the use of older antipsychotic medications (typical antipsychotics) and newer antipsychotic medications (atypical antipsychotics) for the outcome of developing type 2 diabetes.
We included an additional 29 studies with 2481 participants assessing one or more of our secondary outcomes. All studies were conducted in hospital settings and tested pharmacological interventions. No study examined organisational interventions. Only one study evaluated an intervention aimed at changing people's behaviour, but it also included a pharmacological intervention.
For the outcome of study drop-outs (how many people drop out of a study before it ends), we did not find evidence of a difference when participants were treated with atypical antipsychotics, compared with those who were treated with typical antipsychotics. This was also the case in studies comparing treatment with metformin (a medication used to treat diabetes) with placebo (pretend treatment), and those comparing treatment with melatonin (a hormone that regulates sleep) with placebo. Very low-certainty evidence from one study suggests that drop-outs may be higher among participants treated with a tricyclic antidepressant, compared with participants treated with selective serotonin reuptake inhibitors (another type of antidepressant).
We did not find evidence of a difference in fasting blood glucose levels in comparisons between atypical and typical antipsychotics, metformin and placebo, or tricyclic antidepressants and selective serotonin reuptake inhibitors. We did find that fasting blood glucose levels are likely to be lower in participants treated with melatonin, compared to those given placebo.
Body mass index was lower for participants receiving metformin compared with those receiving a placebo, and for participants who received typical antipsychotics, compared with those who received atypical antipsychotics.
Cholesterol levels were lower in participants who received typical antipsychotics, compared with those who received atypical antipsychotics.
We did not find evidence of a difference in waist circumference or blood pressure for any of the intervention groups of the included studies.
Certainty of the evidence
The only study assessing prevention of type 2 diabetes provided low-certainty evidence. The certainty of evidence was reduced because the study was small, and several important aspects of it were at high risk of bias. The other studies reporting secondary outcomes generally provided moderate- to high-certainty evidence for these outcomes.
Conclusions
For people with mental health conditions in LMICs, we do not know what is the best way to prevent type 2 diabetes. Only one of the included trials provided low-certainty evidence on diabetes prevention. Further research should focus not just on pharmacological interventions, but should also include behaviour change and organisational interventions, to learn whether such interventions can be effective and appropriate in LMIC settings.
Only one study reported data on our primary outcome of interest, providing low-certainty evidence that there may be no difference in risk between atypical and typical antipsychotics for the outcome of developing type 2 diabetes. We are therefore not able to draw conclusions on the prevention of type 2 diabetes in people with mental disorders in LMICs.
For studies reporting on secondary outcomes, there was evidence of risk of bias in the results. There is a need for further studies with participants from LMICs with mental disorders, particularly on behaviour change and on organisational interventions targeting prevention of type 2 diabetes in these populations.
The prevalence of type 2 diabetes is increased in individuals with mental disorders. Much of the burden of disease falls on the populations of low- and middle-income countries (LMICs).
To assess the effects of pharmacological, behaviour change, and organisational interventions versus active and non-active comparators in the prevention or delay of type 2 diabetes among people with mental illness in LMICs.
We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase and six other databases, as well as three international trials registries. We also searched conference proceedings and checked the reference lists of relevant systematic reviews. Searches are current up to 20 February 2020.
Randomized controlled trials (RCTs) of pharmacological, behavioural or organisational interventions targeting the prevention or delay of type 2 diabetes in adults with mental disorders in LMICs.
Pairs of review authors working independently performed data extraction and risk of bias assessments. We conducted meta-analyses using random-effects models.
One hospital-based RCT with 150 participants (99 participants with schizophrenia) addressed our review's primary outcome of prevention or delay of type 2 diabetes onset. Low-certainty evidence from this study did not show a difference between atypical and typical antipsychotics in the development of diabetes at six weeks (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.03 to 7.05) (among a total 99 participants with schizophrenia, 68 were in atypical and 31 were in typical antipsychotic groups; 55 participants without mental illness were not considered in the analysis).
An additional 29 RCTs with 2481 participants assessed one or more of the review's secondary outcomes. All studies were conducted in hospital settings and reported on pharmacological interventions. One study, which we could not include in our meta-analysis, included an intervention with pharmacological and behaviour change components. We identified no studies of organisational interventions.
Low- to moderate-certainty evidence suggests there may be no difference between the use of atypical and typical antipsychotics for the outcomes of drop-outs from care (RR 1.31, 95% CI 0.63 to 2.69; two studies with 144 participants), and fasting blood glucose levels (mean difference (MD) 0.05 lower, 95% CI 0.10 to 0.00; two studies with 211 participants). Participants who receive typical antipsychotics may have a lower body mass index (BMI) at follow-up than participants who receive atypical antipsychotics (MD 0.57, 95% CI 0.33 to 0.81; two studies with 141 participants; moderate certainty of evidence), and may have lower total cholesterol levels eight weeks after starting treatment (MD 0.35, 95% CI 0.27 to 0.43; one study with 112 participants).
There was moderate certainty evidence suggesting no difference between the use of metformin and placebo for the outcomes of drop-outs from care (RR 1.22, 95% CI 0.09 to 16.35; three studies with 158 participants). There was moderate-to-high certainty evidence of no difference between metformin and placebo for fasting blood glucose levels (endpoint data: MD -0.35, 95% CI -0.60 to -0.11; change from baseline data: MD 0.01, 95% CI -0.21 to 0.22; five studies with 264 participants). There was high certainty evidence that BMI was lower for participants receiving metformin compared with those receiving a placebo (MD -1.37, 95% CI -2.04 to -0.70; five studies with 264 participants; high certainty of evidence). There was no difference between metformin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels.
Low-certainty evidence from one study (48 participants) suggests there may be no difference between the use of melatonin and placebo for the outcome of drop-outs from care (RR 1.00, 95% CI 0.38 to 2.66). Fasting blood glucose is probably reduced more in participants treated with melatonin compared with placebo (endpoint data: MD -0.17, 95% CI -0.35 to 0.01; change from baseline data: MD -0.24, 95% CI -0.39 to -0.09; three studies with 202 participants, moderate-certainty evidence). There was no difference between melatonin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels.
Very low-certainty evidence from one study (25 participants) suggests that drop-outs may be higher in participants treated with a tricyclic antidepressant (TCA) compared with those receiving a selective serotonin reuptake inhibitor (SSRI) (RR 0.34, 95% CI 0.11 to 1.01). It is uncertain if there is no difference in fasting blood glucose levels between these groups (MD -0.39, 95% CI -0.88 to 0.10; three studies with 141 participants, moderate-certainty evidence). It is uncertain if there is no difference in BMI and depression between the TCA and SSRI antidepressant groups.