PREVENTION OF TYPE 2 DIABETES

Adults at high risk for type 2 diabetes who had received either lifestyle intervention or metformin in the 3-year Diabetes Prevention Program (DPP) and continued in the Diabetes Prevention Program Outcomes Study (DPPOS) were less likely to develop diabetes than patients in the placebo group over an average 22-year follow-up.  

DPPOS chair David M. Nathan, MD, and other study investigators presented findings last week during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

At the end of the DPP, conducted in 1996-2001, patients in the lifestyle-intervention or metformin group were 58% and 31% less likely to have incident diabetes, respectively, than patients in the placebo group.

Now, 22 years after they enrolled in the DPP, patients were on average 72 years old and those in the original lifestyle intervention or metformin group were 25% and 18% less likely to have diabetes, respectively.

And participants who did not develop diabetes had significantly lower rates of eye, kidney, and major cardiovascular disease, at 57%, 37%, and 39%, respectively, according to a statement from the ADA.

"What we have shown is that diabetes prevention is possible," Nathan, from Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News in an interview.

Unique Long-Term Study 

The DPP participants were at very high risk for diabetes, Nathan stressed.

"Their glucose levels were rising. They were overweight, if not obese, and we also overrecruited in ethnic and racial groups that are at particularly high risk — African Americans, Hispanic Americans, American Indians, and Asian Americans."

This unique, long-term study showed "a pretty remarkable — and not unexpected, some may say — reduction in eye disease, kidney disease, and major cardiovascular disease in people who did not develop diabetes," he noted.

"I think it is important for providers and patients with prediabetes to know that even after 22 years, adults at high risk for diabetes have continued to benefit from metformin or prior intensive lifestyle modification in preventing or delaying" diabetes, Christine Lee, MD, told Medscape Medical News in an email.

Lee is program director of the Division of Diabetes, Endocrinology, and Metabolic Diseases, at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Lifestyle Modification Better for Prevention in Adults > 60 Years

In the DPP, 3234 patients at high risk of developing diabetes were randomized to receive placebo or metformin (850 mg twice a day) or an intensive lifestyle counseling program that aimed for 7% weight loss and 150 minutes of moderate exercise per week.

At the end of the DPP, 88% of participants (including those who had developed diabetes) entered the DPPOS; those who were taking metformin stayed on it and all three groups received less intensive lifestyle counseling.As reported earlier, 15 years after enrolling in the DPP, 55% of participants in the lifestyle group and 56% of those in the metformin group had developed diabetes, compared with 62% of those in the placebo group.

At 22 years, 75% of patients from the DPP who were still alive were still participating in the DPPOS.

"The new findings did not show that taking metformin can prevent cancer, cardiovascular disease, or diseases of the eyes and kidney caused by diabetes," Lee pointed out.

However, "the data suggest that there may be some preventive effects of metformin for these outcomes in adults younger than 45 years [eg, a trend to less stroke], but these outcomes were more infrequent in this younger age group and further studies are needed before conclusions can be made for this age group."

"Conversely, there appeared to be a greater risk for kidney disease with metformin in older adults," she continued.

Therefore, "when balancing that risk [from metformin]" with prior, and newer, results that respectively show lifestyle modification works better than metformin for preventing diabetes in older adults, and can also decrease the risk of frailty in this same group, "patients ages 60 and older at high risk for diabetes should focus on intensive lifestyle modification for diabetes prevention," according to Lee.

Metformin is not approved for diabetes prevention in the United States, and it is unlikely that any of the several manufacturers of generic metformin would file a new drug application for this use with the US Food and Drug Administration, according to Nathan.

Widespread Prediabetes, Few Referrals for Community DPPs

In the United States, an estimated 30 million people have diabetes (mostly type 2), including about 7 million not yet diagnosed, Nathen said, and another 90 million have prediabetes.

More research is needed to be able to identify which patients with prediabetes are most vulnerable to developing diabetes and would benefit most from prevention interventions, he stated.

Similarly, Lee said that the current findings "highlight the importance of trying to further understand differences in how metformin or lifestyle modification work in adults at high risk for diabetes."

"Research to better identify who can benefit most from metformin or lifestyle will help providers offer patient-centered approaches for diabetes prevention," she said.

In the meantime, and as previously reported, the US Preventive Services Task Force and the ADA recommend screening and lifestyle counseling to achieve weight loss and reduce diabetes risk in high-risk adults, and diabetes prevention programs are covered by Medicare, many commercial health plans, and some Medicaid and state employee health plans.

About 2 years ago, the Center for Medicare and Medicaid Services began funding the diabetes prevention lifestyle program for qualifying Medicare beneficiaries at high risk of diabetes, said Nathan, and the program is available in many US communities.

And as previously reported, the turnkey lifestyle program to prevent diabetes by the US Centers for Disease Control and Prevention (CDC) replicates the DPP intervention and is offered by 244 YMCAs at more than 1100 locations.

Patients receive coaching from trained individuals about making long-term dietary changes, increasing physical activity, and overcoming challenges to maintaining weight loss and a healthy lifestyle. Counseling is given in 22 sessions over 1 year.

However, few physicians are referring patients with prediabetes to the program. According to a 2019 CDC study, only 5% of individuals with prediabetes and 0.4% of those with an elevated risk of diabetes had been told by their physician to participate in a diabetes prevention program (JAMA Netw Open. 2019;2:E193160).

DPPOS is supported by the NIDDK, National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute on Aging, National Eye Institute, Office of Research on Women's Health, and CDC. Merck supplied the metformin.  

ADA 2020 Scientific Sessions. June 16, 2020.   

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