Progression from Insulin Resistance to T2DM
- Visceral fat → insulin resistance in muscle and liver
- Pancreatic beta cells compensate by producing more insulin → hyperinsulinaemia
- Beta cell exhaustion begins — insulin output falls despite high demand
- Postprandial glucose spikes (IGT)
- Fasting glucose rises — type 2 diabetes develops
Medication Ladder
| Step | Drug | Mechanism | Benefits Beyond Glucose |
|---|---|---|---|
| 1st line | Metformin | Reduces hepatic glucose output; improves sensitivity | Weight-neutral; cardiovascular benefit; cheap |
| Add-on | SGLT2 inhibitors (empagliflozin, dapagliflozin) | Block glucose reabsorption in kidney | Heart failure & CKD benefit; weight loss; low hypo risk |
| Add-on | GLP-1 agonists (semaglutide, liraglutide) | Incretin effect + satiety + slows gastric emptying | Significant weight loss; CVD benefit; reduced mortality |
| Add-on | DPP-4 inhibitors (sitagliptin) | Enhances incretin effect | Weight-neutral; well tolerated |
| Add-on / later | Sulphonylureas (gliclazide) | Stimulates insulin secretion | Low cost; hypoglycaemia risk |
| Final | Insulin | Direct replacement | Most effective; weight gain |
Weight Loss Achieves RemissionThe DiRECT trial showed 46% of people achieved HbA1c <48 mmol/mol (remission) at 1 year with a very low calorie diet (800 kcal/day for 3–5 months). NHS Type 2 Diabetes Path to Remission programme now available.
Can type 2 diabetes be cured?
Cure is not possible, but remission (HbA1c <48 mmol/mol without medication for ≥3 months) is achievable with significant weight loss. The longer diabetes has been present, the harder remission is to achieve.
What is the best diet for type 2 diabetes?
Mediterranean diet and low-carbohydrate diets both show strong evidence. Reducing refined carbohydrates, sugar, and ultra-processed foods while increasing fibre, vegetables, and healthy fats improves glycaemic control.
How does semaglutide (Ozempic/Wegovy) work?
It's a GLP-1 receptor agonist that mimics the gut hormone GLP-1 — stimulating insulin release in response to food, suppressing glucagon, reducing appetite, and slowing gastric emptying. It causes significant weight loss (10–15%).
What are the complications of untreated type 2 diabetes?
Microvascular: diabetic retinopathy (blindness), nephropathy (kidney failure), neuropathy (pain, foot ulcers, amputation). Macrovascular: heart attack, stroke, peripheral arterial disease.
Medical Disclaimer: This page is for general education only and does not replace professional medical advice. Always consult a qualified healthcare provider.