Cardiometabolic risk

Comprehensive Care in Patients With CVD and Diabetes

Yehuda Handelsman, MD

Metabolic Institute of America

Handelsman Y. Comprehensive care in patients with CVD and diabetes [published online July 22, 2019]. Cardiology Consultant.


Diabetes medications reduce hyperglycemia, but trials performed within the last 30 to 40 years have failed to show significant reduction in cardiovascular macrovascular disease. Historically, cardiologists generally did not see patients with diabetes as having very high risk for cardiovascular disease (CVD) and, therefore, did not think that managing glucose in these patients was important.

That all changed in 2015 after the EMPA-REG trial showed that empagliflozin—a new sodium-glucose co-transporter 2 (SLGT-2) inhibitor—not only improved hyperglycemia in patients with diabetes but also reduced CVD mortality by 37%.1 A year later, results of the LEADER trial showed similar reductions in CVD outcomes, including cardiovascular mortality, with use of liraglutide.2

From this point on, cardiologists believed they were experiencing a paradigm shift away from glucose control medications to this new class of drugs that showed reduction in CVD outcomes as well. In fact, last year at the annual meeting of the American Society of Preventive Cardiology (ASPC), many of the cardiologists in attendance expressed concerns about the use of diabetes drugs such as metformin and insulin. Instead, they wanted to only treat patients with SGLT-1 and SGLT-2 inhibitors. In response to these reactions, the chair of the meeting, Peter Toth, invited me to speak at this year’s ASPC annual meeting about the importance of hyperglycemia and its management.

How Hyperglycemia Affects the Body

In patients with diabetes, hyperglycemia causes glycation of the organs and proteins, and changes the characteristics of nerves and blood vessels. When the small blood vessels are affected, the damage to organs happens quickly. Conversely, when large blood vessels are affected, the damage could take longer to see.

We know that hyperglycemia can cause blindness, neuropathy, nephropathy, coma, or limb/phalange amputation. And for some patients, going blind or losing a leg might be more devastating than having a heart attack. Therefore, we have to address microvascular and macrovascular disease.

From several studies, we have seen long‑term “legacy” results. In particular, the United Kingdom Prospective Diabetes Study (UKPDS) did not show reduction in CVD at the end of the trial.3 Ten years after the study completed, the people whose glucose was better controlled at the end of the trial had less CVD and mortality. That is called the legacy effect. We have also seen that in a couple other studies, including ones that evaluated people with type 1 diabetes.

We know from many epidemiologic studies that the higher the A1c measuring glucose, the more complications patients have. What we have not shown, or have not shown well, is that intervention helps, because our studies are short term. We see better results with controlling cholesterol. Even that typically takes 3.5 to 4 years to show results.

People who have had diabetes for at least 10 years will likely already have kidney disease. And people with diabetes and kidney disease have a huge risk for CVD. Therefore, it is important that when we treat people with diabetes, we do not just look at one particular drug for diabetes that may also have an impact on CVD. We need to address all the risk factors comprehensively.

Utilizing a Comprehensive Approach

We know that people with diabetes often have issues with lipids, blood pressure, and coagulation, and so we endocrinologists treat them comprehensively to reduce CVD. Diabetes is not a simple disease. It is not only a glucose disease, and it is not only a macrovascular disease. Diabetes is complex. Patients with diabetes typically also have hyperglycemia, hypertension, and/or dyslipidemia. In many centers, cardiologists now realize that maybe they should create a cardiometabolic center, where they have a cardiologist, an endocrinologist, a nephrologist, and maybe a gastroenterologist or liver specialist.

For example, when I have a patient with arrhythmia or congestive heart failure, I would send him or her to the cardiologist—even though I know these heart problems come from diabetes and I may be able to manage some aspects of it. We have to address the whole comprehensive aspect of patients with diabetes and not just focus on just one aspect of the disease, as important as it is, and say nothing else matters.

Yehuda Handelsman, MD, is a practicing endocrinologist and the medical director of and principal investigator at the Metabolic Institute of America in Tarzana, California.



  1. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOMES investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128. doi:10.1056/NEJMoa1504720.
  2. Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee on behalf of the LEADER Trial investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322. doi:10.1056/NEJMoa1603827.
  3. King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes [published online December 24, 2001]. Br J Clin Pharmacol.