Long term prevention of type 2 diabetes - is it possible?

• Long term prevention of type 2 diabetes is possible in people at high risk of the disease

• Type 2 diabetes can be prevented by taking the drug metformin or with lifestyle interventions involving weight loss and exercise

• These interventions can also reduce the risk of eye, kidney and major cardiovascular disease in those who do not develop diabetes

• Another drug called Farxiga (dapagliflozin) may also help prevent type 2 diabetes

DPPOS confirms 22 years on that long term prevention of type 2 diabetes is possible

Long term prevention of type 2 diabetes is possible according to the results of the Diabetes Prevention Program Outcomes Study (DPPOS), which followed the participants in the study for an average of 22 years.

DPPOS was initiated following the success of the Diabetes Prevention Program (DPP), which was a trial that ran from 1996 to 2001 in people at high risk of type 2 diabetes. DPP included people who were at high risk of type 2 diabetes because they were overweight or obese and had blood glucose levels that were higher than normal, but not high enough to be diagnosed with diabetes.

DPP looked at whether an intensive lifestyle program or taking metformin, a medication already used to treat type-2 diabetes, could be used to prevent or delay the onset of the disease. DPP produced positive results showing that after an average of three years:

• Lifestyle interventions (aimed at achieving and maintaining a 7 percent weight loss and doing a minimum of 150 minutes of moderate intensity exercise every week), reduced the risk of developing type 2 diabetes by 58 percent compared with placebo

• Taking metformin 850 mg twice a day reduced the risk of developing type 2 diabetes by 31 percent compared with placebo.

Of the 3234 people enrolled in the DDP trial, 88 percent went on to be included in DPPOS - the longest and largest type 2 diabetes prevention study running. All participants in DPPOS were offered group-implemented lifestyle intervention. The original metformin group also continued to receive the medication, while the placebo group was discontinued.

Twenty-two years after researchers began following people at high risk of type 2 diabetes, results from DPPOS showed that:

• Participants in the original lifestyle intervention and metformin groups reduced their risk of developing type 2 diabetes by 25 percent and 18 percent, respectively
• Participants who did not develop type 2 diabetes had a 57 percent and 37 percent lower risk of developing early changes of eye and kidney disease, respectively
• Among the people who did not develop type 2 diabetes, 39 percent demonstrated a lower risk of major cardiovascular disease complications including heart attack
• Participants in the lifestyle lifestyle intervention group were at reduced risk of becoming frail
• Treatment with metformin resulted in favorable trend towards a reduction in the risk of stroke and cardiovascular events in participants who began taking the drug before the age of 45
• Metformin therapy was associated with a slight increase in kidney disease in the oldest participants who received it
• No significant benefit was observed from lifestyle interventions or metformin therapy in terms of the development of heart disease, diabetic retinopathy or kidney disease

DAPA-HF also shows that type 2 diabetes prevention is possible

DAPA-HF is another trial that suggests a role for Farxiga (dapagliflozin), another medication already used to treat type 2 diabetes, in the prevention of the disease.

Unlike DPPOS, this trial only followed participants for an average of about 18 months and the trial was not primarily focused on the prevention of type 2 diabetes. Instead, DAPA-HF was focused on preventing worsening heart failure or death due to cardiovascular causes in 4744 people with heart failure and a reduced ejection fraction. It included people with and without type 2 diabetes.

The key finding from DAPA-HF was that Farxiga was beneficial in reducing the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction, which resulted in the US Food and Drug Administration (FDA) granting the drug approval for this indication.

However, another interesting finding from this study was that people who did not have type 2 diabetes at the beginning of the trial were 32 percent less likely to develop the disease if they received Farxiga compared with those who received placebo.

Farxiga is a sodium-glucose cotransporter 2 (SGLT2) inhibitor and DAPA-HF is the first trial of such a drug to show that they may help prevent type 2 diabetes.

Even those at high risk can take steps to prevent type 2 diabetes developing

The results of DPPOS confirm that being at high risk of type 2 diabetes or having prediabetes does not mean that developing type 2 diabetes is inevitable.

Lifestyle interventions are an option open to many people, although the challenges of sticking to such a program over the long period of time should not be underestimated. Two organizations that offer assistance in this area are the:

• US Centers for Disease Control and Prevention (CDC), which runs the National Diabetes Prevention Program (NDPP)

• Centers for Medicare and Medicaid Services (CMS), which runs the Medicare Diabetes Prevention Program (MDPP)

Metformin is also an option for helping to prevent type 2 diabetes, albeit one that is associated with slightly more risk than lifestyle interventions. However, metformin is currently only approved in the US to treat type 2 diabetes and not for prevention of the disease.

DAPA-HF also suggests a potential role for Farxiga in the prevention of type 2 diabetes, although more research needs to be done in this area.