GLP-1 Clinical Benefits Beyond Weight Loss

Originally developed for type 2 diabetes, GLP-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 agonists improve multiple systems at once. They regulate glucose, lower blood pressure and cholesterol, and reduce inflammation.

Large clinical trials have shown benefits that go far beyond weight loss alone, including lower cardiovascular-event risk and potential protection for the kidneys and liver.

The STEP2 and SURPASS studies showed that GLP-1 drugs help the body control blood sugar safely without increasing the risk of hypoglycaemia.

• Increase insulin release when glucose is high.
• Decrease glucagon, which prevents sugar spikes.
• Lower HbA1c by ~0.6–1.5 percentage points on average.
• Support insulin sensitivity and reduce fatty-liver risk.

These effects improve energy levels and reduce long-term diabetes complications.

Studies including SUSTAIN 6 (on semaglutides) and SURPASS CVOT (on tirzepatide) showed that GLP-1 drugs lower the risk of heart attack, stroke, and cardiovascular death in people with type 2 diabetes and may offer similar protection for others with obesity or metabolic syndrome. They:

• Reduce blood pressure and heart rate variability.
• Improve cholesterolDecrease inflammation in blood vessels.
• May stabilise atherosclerotic plaques and improve endothelial health.

GLP-1 medicines may help treat non-alcoholic fatty-liver disease (NAFLD) and its more severe form, NASH (steatohepatitis). More research is needed on this subject though. 

• Reduce liver fat and inflammation.
• Improve insulin sensitivity in the liver.
• Lower liver-enzyme markers (ALT, AST).
• Encourage weight-independent metabolic benefits.

GLP-1 therapy appears to protect kidney function by improving blood flow and lowering inflammation, according to post hoc analysis of the SUSTAIN 6 and LEADER studies. GLP-1 medication:

• Reduces leaking of albumin in urine, an early marker of kidney stress.
• Improves renal microcirculation.
• Helps regulate blood pressure and glucose, easing kidney workload.

STEP data appears to show that GLP-1’s lower chronic inflammation, a root cause of many metabolic and cardiovascular diseases. They:

• Decrease inflammatory markers 
• Improve vascular and adipose-tissue inflammation.
• May contribute to lower overall disease risk through systemic effects.

Many patients report improved confidence, energy, and emotional wellbeing once appetite and weight stabilise.

Better blood-sugar control, reduced fatigue, and less food preoccupation improve daily functioning. Some studies suggest GLP-1 treatment may also reduce cravings for alcohol, nicotine and other illicit drugs. Again, this is an area where more research is ongoing. 

GLP-1 medicines target multiple components of metabolic syndrome at once — obesity, high blood pressure, insulin resistance, and abnormal lipids.

This whole-system benefit explains why they’re being explored as long-term treatments for both weight management and cardiometabolic disease prevention.

Dr Abby Hyams completed her medical training in Bristol and has been a GP for 19 years, spending many of those as a partner in an NHS practice in Hemel Hempstead. She has a particular passion for supporting patients with weight loss and promoting positive behaviour change, helping individuals build sustainable habits that improve their long-term health and wellbeing.

• Marso SP et al. SUSTAIN-6, NEJM 2016
• Marso SP et al. LEADER, NEJM 2016
• Wilding JPH et al. STEP 1, NEJM 2021
• Jastreboff AM et al. SURMOUNT-1, NEJM 2022
• Newsome PN et al. NASH Trial, NEJM 2021
• Gerstein HC et al. REWIND, Lancet 2019
• NICE NG248 (2023); TA875 (2023)
• Leggio L et al. Nat Med 2023 (addiction mechanisms)

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