An article written by Dr Edward Leatham, Consultant Cardiologist © 2025 E.Leatham
A podcast construct and Youtube channel explainer video are available for this story below.
Tags: Glucose, GLP, GLP-1 mimetic, Insulin, Visceral Fat, Coronary heart disease, search website using Tags to find related stories.
At first glance, it sounds like a contradiction.
Insulin is often described as a fat-storage hormone, especially when people talk about stubborn belly fat. So it’s entirely reasonable to ask how drugs that enhance insulin action — such as GLP-1 medications like semaglutide or tirzepatide — can reduce harmful visceral fat, lower the risk of heart attack and stroke, and possibly even influence long-term cancer risk.
The answer is not that insulin is “good” or “bad”. It’s about how insulin behaves over time, why it becomes chronically elevated in modern life, and how GLP-1 therapies restore a healthier metabolic rhythm.
Once that distinction is clear, the paradox disappears.
Insulin is essential — but constant insulin is a problem
Insulin is vital. It allows glucose from food to enter cells and be used for energy.
In a healthy system:
- insulin rises mainly after eating carbohydrates (sugars and starches)
- as glucose is cleared, insulin falls again
- protein causes only a modest insulin rise
- fat causes very little insulin release
This rise-and-fall pattern allows the body to switch between storing and burning energy.
Problems arise when insulin is repeatedly stimulated and rarely allowed to fall. This doesn’t happen because of one meal or one spike. It develops gradually, over months and years, as part of insulin resistance.
Where the problem often begins: loss of muscle in mid-life
Although insulin resistance can (and does) happen at any age, as a consequence of an extremely high sugar environment, for many of us, it only creeps in once skeletal muscle mass starts to shrink in our 30s.
Skeletal muscle is the body’s main “sink” for glucose after meals. Around 70–80% of glucose disposal occurs in muscle.
In mid-life, several things often happen together:
- people move less and few invest in resistance training
- upper-body and fast-twitch muscle fibres are lost
- muscle becomes less responsive to dietary protein
- protein intake is often inadequate or poorly distributed
In the absence of sufficient availability of amino acids and skeletal workload, the body quietly breaks down muscle instead to supply amino acids for tissue repair and immune function. This happens slowly and often goes unnoticed.
The consequence is critical:
there is less muscle available to absorb glucose and we start to become relatively insulin resistant.
In the modern day world of high and rapid carbohydrate intake, blood glucose therefore remains higher for longer. The pancreas compensates by releasing more insulin. Over time, insulin exposure becomes prolonged and repetitive — not because of overeating alone, but because the body has lost metabolic capacity.
Case 1: What chronic insulin demand looks like on a glucose monitor
One of our patients with established coronary heart disease wore a continuous glucose monitor (CGM) for a week before starting GLP-1 therapy (used off-label at the time to reduce cardiovascular risk).
We cannot yet measure insulin continuously in everyday practice. However, because insulin is released largely in response to rising glucose after carbohydrate intake, glucose patterns act as a useful surrogate for insulin exposure.
Before treatment, his CGM showed:
- frequent glucose spikes after meals
- a persistently elevated baseline glucose, even between meals and overnight
This pattern suggests prolonged glucose exposure and repeated insulin demand throughout the day.
Upper panel Baseline One week of continuous glucose monitor (CGM) result
The panel above shows both glucose spikes and high basal glucose. The panel below is his CGM 6 months after taking Tirzepatide 5 mg, without a major change in his diet or lifestyle – during which time his weight dropped 7 Kg and his HbA1C dropped from a prediabetic value of 44 to 34 mmol/mol. It shows not only a dramatic drop in glucose spikes, but an obviously lower basal glucose value. The implication is that medication and/or drop in visceral adipose tissue greatly improved his insulin sensitivity
Lower panel – CGM on same patient 12 months later taking GLP-1 mimetic injection weekly.
When “safe” fat storage fills up, fat spills over
Not all fat behaves the same way.
Fat under the skin (subcutaneous fat) is relatively safe. In some people it can expand without major metabolic harm. In others, its capacity is limited by genetics, inflammation, or scarring.
When this “safe” storage fills up, excess energy driven by insulin has to go somewhere else.
At that point, fat is redirected into ectopic depots — particularly the liver and visceral fat, the fat stored deep inside the abdomen around the organs. This process is often called metabolic spillover.
The liver becomes the traffic controller
As muscle insulin resistance persists and fat tissue becomes less responsive to insulin’s ability to suppress fat release, more fatty acids circulate in the blood.
The liver is exposed to:
- excess dietary sugars, especially fructose
- excess glucose from.digestion of carbohydrates consumed (poor muscle uptake)
- excess fatty acids (from insulin-resistant fat)
It responds by converting this surplus into triglyceride and exporting it as VLDL particles — effectively redistributing energy throughout the body.
Some of this energy ends up stored as visceral fat, adding petrol to the fire. VLDL particles, once shed of triglycerides, become small dense LDL (sdLDL) which are hard to clear from the circulation. sdLDL is considerably more atherogenic than standard ‘fluffy’ LDL and a potent risk factor for coronary atherosclerosis.
Visceral fat accumulation is therefore not simply insulin “pushing fat into the belly”. It reflects a system under metabolic overload, unfolding over weeks and months, with potentially deadly consequences.
Why visceral fat is dangerous
Visceral fat in metabolic disease is typically insulin resistant, not insulin sensitive. It is also more lipolytic, meaning it releases fatty acids easily.
This makes it particularly harmful because it:
- delivers fatty acids directly to the liver
- worsens liver insulin resistance
- drives inflammation
- drives up sdLDL that cannot easily be removed by LDL receptors (and is principle cause of coronary artery disease)
- accelerates cardiovascular disease
Visceral fat becomes both a marker of metabolic overload and a driver of further damage.
Case 2: Seeing visceral fat directly on CT
Another patient with CT-detected coronary atherosclerosis and a raised fat attenuation index (FAI) — a marker of coronary inflammation — showed a glucose profile on CGM very similar to the first case.
He underwent a low-dose CT scan to quantify visceral fat before starting tirzepatide 5 mg weekly, and a repeat CT three months later.
Before treatment, his visceral fat area measured 211 cm², placing him in a high metabolic-risk category. After just three months, it had fallen to 123 cm², within the normal range. This degree of change cannot be explained by calorie reduction alone. It reflects a rapid reduction in metabolic spillover, improved insulin dynamics, and reduced liver fat export.
What GLP-1 drugs actually do
GLP-1 therapies do not exaggerate pathological insulin signalling. They restore physiological insulin behaviour.
They do this by:
- reducing appetite and food reward
- lowering carbohydrate load
- slowing gastric emptying so glucose enters the bloodstream more gradually
- smoothing post-meal glucose rises
- lowering baseline glucose and insulin exposure over time
As chronic insulin exposure falls, the pressure driving ectopic fat storage eases. The liver exports less fat, and visceral fat — which expanded as part of overflow — becomes metabolically vulnerable.
Why belly fat often falls before weight
Visceral fat does not disappear overnight. But once metabolic pressure is relieved, it is often mobilised earlier than subcutaneous fat.
This is why patients often notice:
- a shrinking waist
- clothes fitting differently
- improved blood pressure and glucose
before dramatic changes appear on the scales.
Why this protects the heart — and possibly more
By reducing visceral fat and correcting the insulin-resistant environment that created it, GLP-1 therapies improve the biology that drives cardiovascular disease.
This translated into real outcomes in the SELECT trial, where semaglutide reduced heart attacks, strokes and cardiovascular deaths by around 20% in people with established heart disease without diabetes. The table below shows this is is a comparable effect to statins in secondary prevention.
Visceral fat is also linked to insulin-like growth factor signalling, inflammation and impaired immune surveillance, mechanisms that may help explain associations between visceral fat and certain cancers. While GLP-1 drugs are not cancer treatments, reducing this metabolic stress may have broader long-term implications.
The bottom line
GLP-1 drugs do not reduce fat despite insulin.
They reduce fat because they:
- lower chronic insulin exposure
- improve insulin sensitivity
- reduce liver fat and lipid spillover
- dismantle the conditions that allow visceral fat to accumulate
What looks like a paradox is actually a restoration of metabolic balance.
When that balance is restored, visceral fat — dependent on constant metabolic pressure — cannot survive.
Downloadable short paper with references 2025
References
- Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126:1301–13.
- Holst JJ. The incretin system in healthy humans: the role of GLP-1 and GIP. Diabetologia. 2004;47:357–66.
- Horowitz M, Nauck MA. To be or not to be… gastric emptying and GLP-1. Diabetes Care. 2006;29:2573–8.
- SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in patients with overweight or obesity. N Engl J Med. 2023.
- Renehan AG, et al. Body-mass index and incidence of cancer. Lancet. 2008;371:569–78.
- Thorsson B, et al. Visceral adipose tissue and cancer risk in the AGES–Reykjavik Study. Obesity. 2019;27:1316–23
Related posts
- How to Reduce Visceral Fat Without Medication
- Why everyone is talking about VAT
- Examples of CT VAT scans and normal ranges for VATI
- Turn the Thermostat Down: How a Cooler Home May Improve Insulin Sensitivity and Reduce VAT
- THE CHOICE: How Cardiologists Operate GLP-1 Mimetics in Practice
- Biofeedback: CGM metrics improve after just 4 weeks of dietary intervention
- What Your Glucose Curve Is Trying to Tell You: Why Continuous Glucose Monitoring Matters Long Before Diabetes
- How to Lose Visceral Adipose Tissue (VAT) and Improve Metabolic Health: A Guide to Sustainable Weight Loss
- Protein, Sarcopenia, and the Pursuit of Healthspan
- Why Protein Matters More Than Ever as We Age
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