Type 2 Diabetes and Weight Loss Therapies: The Hype, Hope, and Your Heart

Medications that lower blood sugar have been around for a while, but as far as cardiologists are concerned, truly effective drugs for type 2 diabetes are relatively new. Prior to 2015, when, among other developments, a clinical trial showed that the GLP-1 drug Victoza (liraglutide) could reduce heart disease risk for people with type 2 diabetes, Dr. Daniel Drucker, an endocrinologist at the University of Toronto, frequently found himself on the defensive.

“I would have regular conversations with cardiologists,” he said. “They would go like this: ‘I don't know what you diabetes people are doing. You use these drugs, you think you're lowering blood sugar, you think that you're helping the patient, and 10, 15 years later, I end up seeing them.’”

Now people with type 2 diabetes can choose between multiple GLP-1 drugs with proven heart health benefits. Dr. Alan Moses, board chair of The diaTribe Foundation, led a discussion with a group of experts to explore what has made these drugs so revolutionary and what they might be capable of in the future. The panel included:

• Dr. Daniel Drucker, professor of endocrinology at the University of Toronto
• Dr. Vanita Aroda, director of diabetes clinical research at Brigham and Women’s Hospital and Harvard Medical School
• Dr. Jorge Plutzky, director of preventive cardiology at Brigham and Women’s Hospital

A drug that’s built to last

Our bodies naturally produce glucagon-like peptide-1 (GLP-1) hormones after we eat. These signaling molecules decrease our appetite and make us feel full. They also lower blood sugar by telling the pancreas to release more insulin. This natural version of GLP-1 doesn’t have to last very long to do its job, and it typically gets broken down within minutes. Because of its short lifetime, it didn’t make much sense as a drug when it was first discovered in the 1980s.

However, shortly after researchers identified GLP-1, they found a very similar molecule called exendin-4 in the saliva of Gila monsters. These desert lizards often go a long time between meals, which are massive and take a while to digest. Scientists realized that exendin-4 is essentially a long-lasting version of human GLP-1 that helps Gila monsters manage their binge-eating lifestyle – and a long-lasting GLP-1 molecule does make sense as a drug.

After about a decade of testing and development, the FDA approved Byetta (exenatide), a synthetic version of the Gila monster’s molecule, in 2005. Still, drug developers saw the potential for even longer-lasting GLP-1 drugs than the twice-daily Byetta. 

“We had tremendous progress with first Novo Nordisk, then Eli Lilly, and then many other companies learning that we could tinker with the molecule,” Drucker said. 

Now, the most recognizable GLP-1 drugs Ozempic (semaglutide) and Mounjaro (tirzepatide) only need to be injected once a week.

Helping people settle in for long-term therapy

A medication can only be effective if people are willing to take it. Early on, the gastrointestinal side effects of GLP-1 drugs were a major source of concern. 

"A colleague said to me about 20 years ago, ‘I figured out how the GLP-1 medicines work. You have enough nausea and vomiting all day long, so you’re constantly throwing up, and you lose weight, and so, your insulin sensitization is increased,’” Drucker said.

Since then, the scientific community and medical establishments have come around and recognized the merits of GLP-1 therapy. Healthcare providers have a much better understanding of what it’s like to be on these drugs, and they can coach people through it.

“If we start low, go slow, work with the patient where they make changes in their dietary approaches (minimizing high-fat foods, alcohol, etc.), we can usually get over the initial nausea," Aroda said.

In fact, the onetime hesitancy about GLP-1 drugs has given way to unprecedented levels of hype around their potential as weight loss medications. Now, Aroda’s early conversations with patients are as much about managing expectations as they are about managing side effects.

“This isn’t that quick fix to get into that wedding dress, and then see you later,” she said. “It’s really addressing multiple facets of health as part of chronic therapy.”

In other words, people who start on GLP-1 drugs should expect to be taking them for a long time. That means building them – and all of the costs and effort associated with obtaining and taking them – into your future. For those who can make the investment, these medications can be life-changing. They are effective tools for managing blood sugar and body weight, and they do so while also protecting against heart disease.

A diabetes drug that also helps the heart

Around the time Byetta was approved, scientists made a sobering discovery: Avandia (rosiglitazone), a type of diabetes medication unrelated to GLP-1 that had been approved in 1999, was actually raising people’s risk for heart attacks.

“The FDA and others followed the idea that in order to come forward with a new diabetes drug, you had to prove that it was safe for the heart,” Plutzky said.

That’s why Victoza and subsequent GLP-1 iterations had to go through clinical trials testing their effects on the cardiovascular system. In retrospect, Plutzky thinks the revelation about the specific problems with Avandia might not have warranted such widespread concern about diabetes drugs in general, but he’s happy that drug developers started paying more attention to the connection between diabetes and heart health.

At this point, many trials have demonstrated that GLP-1 drugs – or at least the long-acting ones that have been approved – reduce people’s risk for heart disease. This is true for people with and without type 2 diabetes.

Scientists don’t fully understand how the medications protect the heart, but Plutzky said that it appears to come down to a combination of factors, including reductions in body fat, blood sugar, and whole-body inflammation. According to Drucker, GLP-1 drugs can directly interact with the heart as well, but it’s still not entirely clear how much this matters.

What comes next

There are still a lot of questions about how exactly GLP-1 drugs work in the body and how people can get the most out of them.

Plutzky wants to know if more people could benefit from the heart-protective effects of these medications. For instance, if a person reaches a certain blood pressure value or cholesterol level, would it make sense for their healthcare provider to prescribe a GLP-1 drug to preempt a heart attack?

He said he's also curious if there’s a minimum dose that people can take and still get the benefits.

Aroda thinks more attention should be paid to how bodies change over time. She wants to make sure GLP-1 medications help people stay healthy as they age. This is especially important for women, whose bodies go through different stages with different metabolic and cardiovascular risks.

Finally, Drucker is excited to see the results of ongoing research exploring the effects of GLP-1 drugs on neurological and psychiatric disorders. “Where are the most GLP-1 receptors in the body? It’s in the brain,” he said. 

He acknowledged that GLP-1 medications did not end up having the hoped-for therapeutic effects on Alzheimer’s and Parkinson’s disease, but at the same time, there have been promising signs that the drugs can help people struggling with substance use disorders and other problems. 

“I don’t think GLP-1 is going to be helpful for all of them, but I’m really excited about the randomized controlled trials that are underway,” he said.

The bottom line

It took a little tinkering here and a little convincing there, but now scientists and healthcare providers recognize GLP-1 drugs as the incredible breakthrough therapy that they are. These medications help people manage their blood sugar and body weight, and they have proven heart health benefits. They are not miracle drugs that immediately cure every disease or make a person instantly lose weight, but they are incredibly useful tools for promoting better health.

Learn more about GLP-1s and other diabetes medications here:

• How To Maximize Muscle Health on a GLP-1
• 6 Benefits of Combining Insulin and GLP-1 Drugs
• Benefits of GLP-1s for Type 1 Diabetes and Obesity