By Archana R. Sadhu, MD, as told to Alyson Powell Key
We've known for decades that type 2 diabetes is a very high risk factor for cardiovascular disease. In fact, we've called it equivalent to existing heart disease. So if you have type 2 diabetes, you can think of yourself as having cardiovascular disease, or at least at the highest stage of risk for it.
The Link Between Type 2 Diabetes and Cardiovascular Disease
There are many causes of cardiovascular disease in people with diabetes. One is that glucose levels themselves cause changes within the cardiovascular system that promote the deposit of plaque. This then causes obstructions, particularly in the arteries, which supply blood to the brain, kidneys, and many other organs.
So we know that high glucose levels will promote plaque within the arteries that supply blood to important organs so they can work well. Type 2 diabetes is also closely related to other conditions that may happen at the same time, like obesity, high blood pressure, and high cholesterol. Each of these is its own risk factor for cardiovascular disease.
So it's a complex web. But from my perspective, I see type 2 diabetes in the center with the other conditions around it, raising your risk for a cardiovascular event such as heart attack or stroke. This is the ultimate outcome that we're trying to prevent.
‘Exciting Times’ in Managing Type 2 Diabetes and Cardiovascular Disease
We’ve long known that controlling high blood glucose levels prevents complications that affect the small blood vessels. These include retinopathy, kidney disease, and neuropathy. But we were at a loss about how to prevent complications of the big blood vessels, such as cardiovascular disease.
But new classes of drugs have allowed us to successfully prevent cardiovascular disease. In particular, this includes the GLP-1 receptor agonists and the SGLT-2 inhibitors. So the picture is coming together now with our understanding of what these drugs do for heart health. We know better how we can really improve how people can manage these conditions. So these are exciting times for those of us helping people manage type 2 diabetes.
What Are the Most Effective Treatments for These Two Conditions?
It all depends on your stage of diabetes. With this condition, we have very early stages of insulin resistance progressing all the way through beta cell failure. That’s where you don’t make enough insulin to keep your glucose levels normal. In the earlier stages, drugs to reduce insulin resistance along with lifestyle changes are key to protecting the beta cell’s ability to make enough insulin to regulate your glucose. But when beta cell failure does happen, you just need insulin, which is a highly effective therapy as well.
But in between is where we've seen a complete shift in our treatments. This is before you absolutely need insulin, and you can actually lower insulin resistance. You can enhance your beta cells to perform better and function longer. And that's what drugs like the GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists do. They’ve really revolutionized how we manage type 2 diabetes.
In the past, some of these people may have gone on to insulin therapy, but we can now prevent that by using these drugs. SGLT2 inhibitors are also a great addition to our medication toolbox in this respect.
The great thing about these drugs compared to insulin is that they do not have the risk of causing low blood sugar. Insulin always has that negative side effect. So a lot of us have been prescribing these drugs earlier in the course of diabetes with great success. A1c — the measure of success in diabetes treatment — can be normalized. This has never been readily achievable in the past. Weight, blood pressure, heart health, and metabolism get better.
The Challenges of Managing Type 2 Diabetes and Cardiovascular Disease
Diabetes and cardiovascular risk need a multipronged approach. We have to focus on glucose, blood pressure, cholesterol, and a person’s diet and physical activity habits.
The challenge is knowing when to promote healthy lifestyle habits as the primary approach versus using the right drug therapy. Lifestyle habits are always at the foundation. But we all know they can be difficult for everybody to achieve. When it doesn’t work, we must step forward and say, ‘OK, those efforts have failed or are not as successful as we'd like. Now we need to bump up the treatment and start these new therapies.’ These newer classes of drugs are helping us do that.
For instance, if someone is really far beyond their healthy weight, we can help them by giving GLP1 receptor agonists to help them lose a lot of weight. Then they get positive reinforcement and change their diet and exercise habits along with drug therapy. But whether we should do this in steps or together in a multipronged approach is an individual assessment for each patient. It’s a very patient-centric strategy. It can be challenging to coordinate all those treatments for the patient.
The side effects of these drugs have also been an issue. Nothing comes without side effects in medicine. So while a patient may look to be a great fit for one of these newer classes of drugs, they may not be able to tolerate it because of the side effects. Then we have to go to our secondary therapies. So it's a lot of coordination with other subspecialists. We have to make sure the entire care team works together to use the right therapy for the person.
The Future of Treatment for Type 2 Diabetes and Cardiovascular Disease
So far, we’ve been using a single GLP-1 receptor agonist followed by a dual GLP-1/GIP receptor agonist. Both show remarkable cardiovascular benefits. A third triple agonist, which is not yet FDA-approved, will be coming soon. It has very positive clinical trial results. So we're really looking forward to many medication options.
We have many new drugs in the pipeline. One important category is incretin therapy. This is related to naturally occurring gut hormones. This field is growing fast. There are several trials happening that combine different gut hormones. They lower glucose and weight, protect heart health, and reduce heart-related events.
There are also cholesterol-lowering therapies. Statins are the traditional drug for lowering lipids. They’ve also been shown to directly improve cardiovascular outcomes. PCSK9 inhibitors have been on the scene for some time now, and that class has also grown recently. So addressing heart-related risks from different angles has really helped us manage the needs of people living with diabetes.
While continuous glucose monitors (CGMs) have existed for many years, two companies have just released versions that don't need a prescription. Those with prediabetes or diabetes who aren’t on insulin, or even healthy people, can use them to monitor daily glucose changes. They can then make changes to their lifestyle to prevent diabetes if they're at risk. These early lifestyle changes will significantly lessen cardiovascular risk long term. As the saying goes, “An ounce of prevention equals a pound of cure.”
Also, we now have automated insulin delivery systems that integrate with the CGMs to deliver more individualized and precise dosing, with new products every year. The newest one on the market now is the TWIIST, which was developed as a “do-it-yourself” by patients who were living with type 1 diabetes and wanted better glucose control. It's aimed at being much more individualized than its competitors. This allows for more success in achieving healthy glucose goals and reducing cardiovascular complications.
Weight loss drugs are booming, with many in the pipeline at various stages of the clinical trial process. Amycretin is a new one, and study results just released showed a remarkable weight loss of 22% in people with obesity and overweight after just 36 weeks.
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SOURCE:
Archana R. Sadhu, MD, director, Houston Methodist System Diabetes Program, Houston Methodist, Houston.
