More than just a weight loss drug - the connection between GLP-1s and heart health

Glucagon-like peptide-1 (GLP-1) is a hormone naturally produced by the intestine after we eat. It plays an important role in regulating blood glucose and appetite. It signals your pancreas to produce insulin, tells your brain you’re full, and slows digestion.

GLP-1 medications are lab-made versions of this hormone, so they make you feel full faster, curb appetite, and help control blood sugar by preventing more glucose from going into your bloodstream.

Most GLP-1s are weekly injections, with higher dosages giving stronger effects.

Dr Daniel Chan, a cardiologist at Whangārei Hospital, says that a human’s naturally produced GLP-1 hormone is very short-acting, but these drugs have been developed to have a long-lasting effect.

“Although it was initially created as a diabetic medication, it has more effects beyond that. Its real benefit is how it modifies metabolism and inflammation and how that modifies cardiovascular risk.”

GLP-1 receptor agonists are medicines that mimic some of these effects. Examples of those medicines include dulaglutide (Trulicity), liraglutide (Victoza) and semaglutide (Wegovy).

The connection between obesity, diabetes and cardiovascular disease is well established.

Excess weight is associated with hypertension, abnormal lipid levels, insulin resistance, inflammation, sleep apnoea and other factors that can increase cardiovascular risk.

Emerging evidence from several large cardiovascular outcome trials suggests that some GLP-1 receptor agonists can reduce major cardiovascular events in people with type 2 diabetes who have cardiovascular disease or are at high cardiovascular risk.

Semaglutide (Wegovy) has particularly important evidence because its cardiovascular effects have also been studied in people living with obesity, without diabetes.

One particular GLP-1 trial, SELECT, involved 17,604 adults aged 45 years or older who had established cardiovascular disease and were either overweight or obese, but did not have diabetes.

Participants were randomly assigned to receive weekly semaglutide or a placebo in addition to standard care. The primary cardiovascular outcome was a combination of cardiovascular death, non-fatal heart attack or non-fatal stroke.

Over an average follow-up of almost 40 months, a major cardiovascular event occurred in 6.5% of people receiving semaglutide compared with 8.0% receiving placebo. This represented a 20% relative reduction in the risk of the primary cardiovascular outcome.

Dr Chan says this trial has changed how cardiologists, as opposed to diabetes specialists, think about these medicines.

“This is the main trial that we hang our hat on as cardiologists, because previously we viewed these medications as diabetes treatment only, so it’s expanding that space for us.

"That’s where the real boom and excitement is, in terms of primary and secondary cardiovascular prevention.”

There was also evidence of some improvements in HFpEF (heart failure with preserved ejection fraction), Dr Chan says.

Weight loss itself can improve many cardiovascular risk factors.

Losing excess weight can improve blood pressure, glucose regulation, physical function and other cardiovascular risk factors.

However, the findings from the SELECT trial suggest that weight loss may only be part of the explanation of the cardiovascular effects of GLP-1 medicines.

Dr Chan has considered whether cardiovascular patients benefit from GLP-1 medicines solely because they lose weight.

“That’s a good question, because when you look at the data, you can see that, again, with all the weight loss trials and semaglutide, the maximum weight loss is typically seen somewhere between six and 12 months,” he says.

“But if you look at the cardiovascular benefits — the reduction in MACE (major adverse cardiovascular events) in the SELECT study — the curve started separating really early, before you get significant weight loss.

“So, at least in my mind, although we don’t quite know what the exact mechanism is, there is some additional effect beyond weight loss that improves cardiovascular outcomes.”

Possible contributors include improvements in metabolic function, blood pressure, inflammation, vascular health and fat distribution. However, the exact contributors remain an area of ongoing research.

Inflammation is part of the puzzle, Dr Chan says.

“We’ve shown that atherosclerotic cardiovascular disease is quite complex, and inflammation plays an important role.

"But I don’t think, based on the current literature and evidence, that we’ve found the right balance in terms of how to reduce inflammation to reduce cardiovascular risk, without paying a price with other side effects such as infection,” he says.

“Semaglutide is one of those drugs that, I’m going to argue, has found that sweet spot in reducing inflammation and cardiovascular risk”.

For cardiologists, it raises an intriguing possibility that GLP-1 medicines may become part of a broader cardiometabolic approach to reducing cardiovascular risk.

For people with type 2 diabetes, the type of medication given may not take into account cardiovascular disease, kidney disease, heart failure risk and weight.

This is particularly relevant because cardiovascular disease remains a major cause of illness and death among people living with type 2 diabetes.

Dr Chan says that these medicines should be considered for patients who’ve had a cardiovascular event, and who have a BMI greater than 27.

He is more cautious about a specific group: older, frailer patients close to the weight threshold.

Dr Chan views these drugs as cardiovascular drugs with a weight loss side effect, rather than a weight loss medication with a cardiovascular benefit.

GLP-1 medicines belong in the “same toolkit” as established treatments such as statins, blood pressure medicines and SGLT-2 inhibitors, Dr Chan says.

But, currently, there are many barriers to offering it as part of routine practice, he says.

“The barriers are, one: the funding issue.

"It’s hard to discuss cost, because I think patients are willing to pay that cost for weight loss, or for appearance, but then it’s hard to talk about the same cost for cardiovascular benefit or risk reduction,” Dr Chan says.

“The second barrier is that the evidence doesn’t support starting it in hospital, and that’s when patients are most motivated to take steps to reduce their risk.

“They’ve got the biggest motivation there, whereas if you’re waiting until you see them in clinic six weeks or three months later, the appetite for risk reduction disappears," he says.

For some people, GLP-1s can be highly effective medicines, but they do not come without risks.

The most common side effects involve gastrointestinal disruption.

People may experience nausea, vomiting, frequent diarrhoea, constipation and stomach pain, bloating, indigestion and acid reflux.

Rare and serious risks include gallbladder problems, kidney problems, and pancreatitis.

Healthcare providers consider people’s individual medical history, other medications and potential complications for patients before prescribing GLP-1 medicines.

Weight loss can include a reduction in both fat and lean body mass.

Maintaining nutrition is important, and patients receiving a GLP-1 medicine often still need heart and blood pressure drugs.

GLP1s do not replace every need for cholesterol or blood pressure care.

From 1 September 2026, Pharmac made it easier for New Zealanders living with type 2 diabetes to get funded access to GLP1 receptor agonists (dulaglutide and liraglutide) to treat diabetes.

Previously, patients had to meet very strict criteria related to cardiovascular risk or existing diabeticrelated kidney disease, or meet specific ethnicity criteria.

Both have now been removed. Semaglutide (Wegovy) was approved for use in New Zealand in 2025 for weight management, however, it is not publicly funded.

Dr Chan is cautious about how far funding could realistically extend, but sees a clear case for a defined group of patients, he says.

“I don’t know whether or not (in the New Zealand climate) we can fund it for everyone based on the same SELECT study criteria, but certainly there is a need for people who are struggling with obesity and with recurrent cardiovascular events.”

There is a stigma that can shape funding debates around obesityrelated medicines, he says.

“Obesity is often seen as the patient’s fault, but we know that’s not always the case.

"So, there is a bit of reluctance to fund this from an obesity point of view, but then I flip it back and say it actually is a cardiovascular drug — a 20% reduction in cardiovascular events is just as effective as other therapies we already subsidise.”

GLP-1 medicine research is evolving, and what began as a treatment to improve blood glucose has developed into a major area of research across diabetes, obesity, cardiovascular disease, kidney disease, sleep apnoea and other metabolic health conditions.

If there is one message Dr Chan wants clinicians and patients to take from the emerging evidence, it is to reframe what GLP-1 medicines actually are.

“This isn’t actually a weight loss drug — it’s a cardiovascular risk-lowering drug with a weight loss side effect”.