expert roundtables

Prevention of Type 2 Diabetes: Current Standards and Future Directions

by Serena Cardillo, MD; Rita Rastogi Kalyani, MD, MHS, FACP; and Marie E. McDonnell, MD

Overview

Over the last 2 decades, the use of hemoglobin A1C to more routinely diagnose prediabetes has been a critical step in preventive care. Gaps in prevention include the need for the more aggressive treatment of obesity in certain patients who are at the highest risk for developing type 2 diabetes.

Q:

What are some challenges in prevention, and what are some potential opportunities for improvement in this area?

Serena Cardillo, MD

Fellowship Program Director and Director of Education
Professor of Clinical Medicine and Physician
Division of Endocrinology, Diabetes and Metabolism
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

We can counsel patients with prediabetes about goals for lifestyle changes, but many individuals would also benefit from more structured support between visits, including coaching to help them implement the changes needed to reach their goals.

Serena Cardillo, MD

At present, the standard approach to preventing type 2 diabetes is probably not sufficiently aggressive. We know from the Diabetes Prevention Program Outcomes Study (DPPOS), the largest diabetes prevention study ever conducted, that lifestyle modification in individuals with prediabetes works better than pharmacotherapy with metformin for preventing conversion to diabetes. The DPPOS showed that losing 7% of body weight and exercising 30 minutes per day, 5 days per week can reduce the risk of prediabetes progressing to type 2 diabetes by approximately 60% over the next few years. 

However, patients in the DPPOS had access to coaches, counselors, and nutritionists who worked with them consistently, so the study was not conducted under real-world conditions. The extensive resources used in the study are not typically available in the primary care or endocrinology practice settings, and insurers may not cover nutritional counseling until after patients receive a diagnosis of type 2 diabetes. We can counsel patients with prediabetes about goals for lifestyle changes, but many individuals would also benefit from more structured support between visits, including coaching to help them implement the changes needed to reach their goals. In patients who have tried and failed lifestyle modification, or who perhaps were successful in weight loss and exercise but continued to have hemoglobin A1C levels in the prediabetic range, pharmacotherapy with metformin does work. Patients should receive metformin sooner rather than later if they are at heightened risk. 

Still, even in patients who are medicated, we should not forget to discuss the lifestyle component, which is more impactful than metformin. Time is short during office visits, but clinicians can uncover valuable information by performing a quick lifestyle check-in and helping patients with setting some lifestyle goals. It does not take long, and those changes can be very impactful.

Rita Rastogi Kalyani, MD, MHS, FACP

Editor in Chief, Johns Hopkins Diabetes Guides
Director, Diabetes Management Service
Johns Hopkins Total Pancreatectomy Islet Auto Transplant Program
Associate Professor of Medicine
Johns Hopkins University School of Medicine
Baltimore, MD

“In the ADA guidelines, criteria to consider metformin for those with prediabetes include a body mass index cutoff of 35 kg/m2 or higher, a history of gestational diabetes, or an age of less than 60 years. . . . The benefits of identifying and treating prediabetes pharmacologically have been debated.”

Rita Rastogi Kalyani, MD, MHS, FACP

As noted by Dr Cardillo, the DPPOS results suggest that prevention can be effectively accomplished with lifestyle modification, and lifestyle behavior change is still the cornerstone of diabetes prevention, as reflected in the American Diabetes Association (ADA) guidelines. For the subset of patients who are, for whatever reason, unable to succeed with this approach, more support and additional interventions may be needed.

Weight loss through behavior changes such as diet and exercise can be difficult to maintain long-term. Thankfully, there is now a Medicare-sponsored DPP program that enables any patient with prediabetes who is covered by Medicare to participate in a structured lifestyle intervention that is similar to the DPP program and have it covered. However, this has only been made possible within the past few years.

In terms of medications, we do not have any pharmacotherapy that is approved by the US Food and Drug Administration (FDA) specifically for prediabetes. In the ADA guidelines, criteria to consider metformin for those with prediabetes include a body mass index cutoff of 35 kg/mor higher, a history of gestational diabetes, or an age of less than 60 years (since lifestyle interventions seemed to be more effective in those aged ≥60 years in the DPP). The benefits of identifying and treating prediabetes pharmacologically have been debated. Some of the controversy relates to the lack of demonstrated outcomes data on the complications (ie, does the treatment of prediabetes with metformin help prevent later complications in those who eventually develop type 2 diabetes?). Where preventive care goes from here remains to be seen because there are undoubtedly several areas that need further study.

Marie E. McDonnell, MD

Chief, Diabetes Section
Division of Endocrinology, Diabetes and Hypertension
Director, Diabetes Program
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA

“There is still not enough attention paid to the aggressive treatment of obesity in certain patients who are at the highest risk for developing type 2 diabetes."

Marie E. McDonnell, MD

As suggested by my colleagues, there has been a great deal of focus on controlling obesity as a way of preventing type 2 diabetes. There have been advancements over the past 2 decades, including the introduction of glucagon-like peptide 1 receptor agonists, as well as all of the positive data that emerged with bariatric surgery. Still, there is not enough attention paid to the aggressive treatment of obesity in certain patients who are at the highest risk for developing type 2 diabetes.

Additionally, obesity is still not treated like a disease, even though it is known that obesity is a chronic disorder in which neurological mechanisms that control eating and food-seeking behaviors are permanently altered. As a result, patients who are obese may maintain a higher body weight even if they reduce their calorie intake and increase exercise. Lifestyle modification may promote temporary weight loss, but many patients continue to struggle because we have not yet found a cure for alterations in the neurological pathways that promote increased body weight.

These challenges aside, clinicians do have multiple tools at their disposal now to help control obesity and to lower the risk for developing type 2 diabetes. Medications or metabolic surgery are indicated in select patients. There are presently data supporting pharmacotherapy as a preventive measure for obesity, and there are a number of FDA-approved agents for chronic weight management, including a glucagon-like peptide 1 receptor agonist that is also FDA approved for type 2 diabetes at a different dose. Ultimately, however, prevention begins with what we teach our children about diet, exercise, smoking, and the impact of obesity on all aspects of their health.

References

American Diabetes Association. 3. Prevention or delay of type 2 diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(suppl 1):S34-S39. doi:10.2337/dc21-S003

Davidson MB. Metformin should not be used to treat prediabetes. Diabetes Care. 2020;43(9):1983-1987. doi:10.2337/dc19-2221

Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes study. Lancet Diabetes Endocrinol. 2015;3(11):866-875. doi:10.1016/S2213-8587(15)00291-0

Fagg J, Valabhji J. How do we identify people at high risk of type 2 diabetes and help prevent the condition from developing? Diabet Med. 2019;36(3):316-325. doi:10.1111/dme.13867

Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403. doi:10.1056/NEJMoa012512

Verhaegen AA, Van Gaal LF. Drugs affecting body weight, body fat distribution, and metabolic function-mechanisms and possible therapeutic or preventive measures: an update. Curr Obes Rep. 2021;10(1):1-13. doi:10.1007/s13679-020-00419-5

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