expert roundtables

Advances in the Management of Type 2 Diabetes

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

Overview

Significant advancements in the management of type 2 diabetes have been made within the past 15 years. Newer glucose-lowering medication classes with differing mechanisms of action can treat type 2 diabetes and lower the risks associated with comorbidities such as cardiovascular and renal disease.

Q:

In your opinion, what have been the greatest advances in the management of type 2 diabetes over the past 15 years?

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

“In parallel with the ability to reduce the risk of major adverse cardiovascular events, we have also uncovered the real value of the ability to manage obesity-related diabetes with agents that do not promote weight gain.”

Marie E. McDonnell, MD

In parallel with the ability to reduce the risk of major adverse cardiovascular events, we have also uncovered the real value of the ability to manage obesity-related diabetes with agents that do not promote weight gain. Up until the glucagon-like peptide 1 (GLP-1) receptor agonists, metformin was the only option available in helping patients with type 2 diabetes to lose weight and improve insulin resistance. Previously, patients who developed worsening insulin resistance, weight gain, and beta-cell failure would have been treated with insulin. As reflected in current guidelines, moving to insulin at this point is now considered third-line treatment in poorly controlled type 2 diabetes; we move to insulin later in the progression of the disease, if we must. By contrast, there was no other option 20 years ago. Thus, today, it is extremely important that diabetes care specialists work to place these newer medications ahead of insulin in patients who struggle with obesity-related diabetes, which is the case for millions of Americans and for people around the world.

Regarding advances in team-based care, I think that we still have more work to do; however, there has been some momentum in the past year or so due to the COVID-19 pandemic, particularly because of the quick adaptation to delivering virtual care and remote management. This has been a very effective way to engage a larger group of providers, practitioners, and pharmacists in a more hands-on way to take the Standards of Care treatment algorithm and apply it to patients while, at the same, we engage with patients very routinely and regularly without a lot of burden (ie, they do not have to leave their home). 

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

The most exciting advancement to me has been the progress in our ability to target multiple underlying pathophysiologic defects within type 2 diabetes.”

Serena Cardillo, MD

The most exciting advancement to me has been the progress in our ability to target multiple underlying pathophysiologic defects within type 2 diabetes. Historically, treatment options for patients with type 2 diabetes included metformin, the sulfonylureas, insulin, and the thiazolidinediones, with the primary focus being insulin resistance as the initial and primary driving force behind type 2 diabetes. With insulin and the sulfonylureas, the target became the progressive underlying beta-cell dysfunction and progressive insulin deficiency. The development of novel agents that target defects in incretin physiology, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, reflects a more comprehensive understanding of the underlying pathophysiology. The development of sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy, which targets glucose disposal through the urinary tract, reflects a novel mechanism as well. With these therapeutic advances, we can now apply a broader perspective to targeting multiple underlying pathophysiologic defects in this multifaceted approach to type 2 diabetes that ultimately results in improved glycemic control.

In addition, these novel agents have shifted our focus from a unidimensional therapeutic target in glycemic control to a multidimensional approach that targets longer-term health outcomes for those patients with cardiovascular and renal disease specifically. It is exciting to know that the agents that we are now using, which are quite effective in glucose lowering, are also having a tremendous impact on modifying risk factors and comorbidities—comorbidities that are highly prevalent in this population and carry significant burden for patients.

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

“ . . . one of the biggest advances is that we now have access to very good evidence from large clinical trials showing that the more recently approved glucose-lowering drugs are not only safe but can also reduce cardiovascular and heart failure events.” 

Rita Rastogi Kalyani, MD, MHS, FACP

As my colleagues have noted, over the past 5 to 10 years, there have been several new classes of medications that have been introduced for patients with type 2 diabetes: DPP-4 inhibitors, GLP-1 receptor agonists, and, most recently, SGLT2 inhibitors. And what is exciting is that these new classes offer different mechanisms of action for the treatment of type 2 diabetes. For example, the DPP-4 inhibitors and the GLP-1 receptor agonists act through the incretin pathway while the SGLT2 inhibitors act primarily on the kidney to increase glucose excretion in the urine, which is an entirely new mechanism of action for antihyperglycemic agents.

What is also exciting is that the US Food and Drug Administration requirement of post-marketing cardiovascular outcome trials for any new drug approved for type 2 diabetes since 2008 has resulted in a wealth of data. Such data not only demonstrate cardiovascular safety but also, for some agents, establish cardiovascular superiority, including reducing the risk of major adverse cardiovascular events (ie, nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, or hospitalization for heart failure in patients with type 2 diabetes who have heart failure with reduced ejection fraction). Therefore, one of the biggest advances is that we now have access to very good evidence from large clinical trials showing that the more recently approved glucose-lowering drugs are not only safe but can also reduce cardiovascular and heart failure events.

References

Sattar N. Advances in the clinical management of type 2 diabetes: a brief history of the past 15 years and challenges for the future. BMC Med. 2019;17(1):46. doi:10.1186/s12916-019-1281-1

Sharma A, Pagidipati NJ, Califf RM, et al. Impact of regulatory guidance on evaluating cardiovascular risk of new glucose-lowering therapies to treat type 2 diabetes mellitus: lessons learned and future directions. Circulation. 2020;141(10):843-862. doi:10.1161/CIRCULATIONAHA.119.041022

Tsoutsouki J, Wunna W, Chowdhury A, Chowdhury TA. Advances in the management of diabetes: therapies for type 2 diabetes. Postgrad Med J. 2020;96(1140):610-618. doi:10.1136/postgradmedj-2019-137404

US Food and Drug Administration. Type 2 diabetes mellitus: evaluating the safety of new drugs for improving glycemic control; draft guidance for industry; availability. March 10, 2020. Accessed July 13, 2021. https://www.federalregister.gov/documents/2020/03/10/2020-04877/type-2-diabetes-mellitus-evaluating-the-safety-of-new-drugs-for-improving-glycemic-control-draft

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