Active Engines
✓ Insulin resistance — the root engine
Cells stop responding to insulin. Pancreas compensates by making MORE. Works for years...then fails.
✓ Beta cell exhaustion
Pancreas overworks for decades → beta cells burn out → relative then absolute deficiency
⚠ Cardiovascular engine — the real killer
80% of T2D die from CV disease. Diabetes 2-4x multiplies MI and stroke risk.
✓ Reversibility window — closing
Early T2D is REVERSIBLE with weight loss. 15kg = remission in many. The window closes as beta cells die.
✓ HbA1c oscillation
Average of 90 days of glucose waves. Target <53 mmol/mol (7%). Above = cumulative vascular damage.
✓ Medication ladder
Lifestyle → metformin → GLP-1/SGLT2 → insulin. Each step = one more failed upstream engine.
⚠ Drug Interactions
HIGH · metformin + contrast dye (CT scans)
Hold metformin 48h before IV contrast. Risk: lactic acidosis. Often overlooked.
HIGH · metformin + alcohol excess
Lactic acidosis risk with heavy alcohol. Moderate drinking generally safe.
MEDIUM · SGLT2 inhibitors + UTI/genital infection risk
Glucose in urine = yeast/bacterial growth. Hygiene education important. Also: euglycaemic DKA (rare but serious — stop before major surgery).
MEDIUM · GLP-1 agonists + pancreatitis history
GLP-1 associated with pancreatitis in susceptible patients. Avoid if history of pancreatitis.
Protocol
LIFESTYLE FIRST (not optional)
150min/week exercise + dietary change · Always — even with medication
10-15kg weight loss achieves remission in early T2D. This is the only cure. DiRECT trial: 46% remission at 1yr with low-calorie diet.
Metformin
500mg BD → titrate to 1g BD · Lifelong if tolerated
Cheapest, safest, best evidence. Reduces hepatic glucose output. Does NOT cause hypoglycaemia alone. GI side effects = take with food.
GLP-1 agonist (semaglutide/tirzepatide)
Semaglutide 0.25mg → 1mg weekly / Tirzepatide 2.5mg → 15mg weekly · Long-term
Weight loss + HbA1c reduction. Tirzepatide (Mounjaro) = dual GLP-1/GIP. The best drug in class currently. CV protection proven.
SGLT2 inhibitor (empagliflozin/dapagliflozin)
10-25mg/day · Long-term
Glucose in urine (glucosuria). Also: heart failure protection, kidney protection. Use regardless of glucose if CV/kidney risk present.
Statin (atorvastatin 40-80mg)
40mg nocte · Lifelong
EVERY T2D should be on a statin unless contraindicated. LDL <1.8 mmol/L target if CV risk. The cardiovascular engine is the one that kills.
BP control (ACE inhibitor/ARB)
Target <130/80 · Lifelong
Ramipril/Perindopril + kidney protection. Diabetic nephropathy prevention.
Insulin (late stage)
As per T1D protocol · When beta cells fail
Reaching this point = beta cell exhaustion. Same insulin as T1D but often higher doses (resistance).