What is Type 2 Diabetes?
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterised by insulin resistance and relative insulin deficiency. It is diagnosed by fasting plasma glucose ≥7.0 mmol/L (126 mg/dL), 2-hour OGTT glucose ≥11.1 mmol/L, HbA1c ≥48 mmol/mol (6.5%), or random glucose ≥11.1 mmol/L with symptoms. T2DM carries substantial risk of microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (cardiovascular, cerebrovascular) complications.
Pathophysiology
T2DM develops through progressive beta-cell failure in the context of peripheral insulin resistance. The "ominous octet" of pathophysiological defects includes: decreased insulin secretion, decreased incretin effect, increased glucagon secretion, increased hepatic glucose production, impaired glucose uptake, increased lipolysis, increased glucose reabsorption (kidney), and neurotransmitter dysfunction. Chronic hyperglycaemia drives advanced glycation end-product formation and oxidative stress, mediating microvascular injury.
Clinical Features & Symptoms
- Often asymptomatic in early stages
- Polyuria and polydipsia (osmotic diuresis)
- Fatigue and lethargy
- Blurred vision (osmotic lens changes)
- Recurrent infections (candidiasis, UTIs, skin)
- Slow wound healing
- Peripheral paraesthesia (early neuropathy)
- Acanthosis nigricans (insulin resistance marker)
Diagnosis
Diagnosis by any of: fasting plasma glucose ≥7.0 mmol/L; 2-hour OGTT ≥11.1 mmol/L; HbA1c ≥48 mmol/mol (6.5%); random glucose ≥11.1 mmol/L with symptoms. Asymptomatic patients require two abnormal results on different days. HbA1c may be unreliable in haemoglobinopathies, haemolytic anaemia, or recent blood transfusion.
Current Treatment Guidelines
Lifestyle modification
Class I, Level AMediterranean or low-carbohydrate diet, 150 min/week moderate exercise, weight loss ≥5%. Structured remission programmes (DiRECT trial) achieve T2DM remission in ~50% at 1 year with ≥15 kg weight loss.
Metformin
Class I, Level AFirst-line pharmacotherapy. Reduces HbA1c by 1–2%. Contraindicated if eGFR <30; reduce dose eGFR 30–45. Cheap, weight-neutral, no hypoglycaemia.
SGLT2 inhibitor
Class I, Level A (CVD/HF/CKD)Empagliflozin, dapagliflozin, canagliflozin — add if established CVD, HF, or CKD regardless of HbA1c. Reduce CV death (EMPA-REG OUTCOME), HF hospitalisation, and CKD progression independently of glycaemic control.
GLP-1 receptor agonist
Class I, Level A (established CVD)Semaglutide (preferred), liraglutide, dulaglutide — add if established CVD or high CV risk. Superior weight loss, HbA1c reduction, and CV outcomes vs other agents. Semaglutide 2.4 mg (Wegovy) approved for obesity.
Tirzepatide
Class I (ADA 2024)Dual GIP/GLP-1 agonist. SURPASS trials: superior HbA1c and weight reduction vs semaglutide. ADA 2024 includes as second-line option. FDA approved for T2DM (Mounjaro) and obesity (Zepbound).
CGM / Automated insulin delivery
Class I, Level AContinuous glucose monitoring now standard of care for all insulin-treated T2DM (ADA 2024). Time-in-range (TIR 70–180 mg/dL) ≥70% as key target alongside HbA1c. Flash glucose monitoring (Libre) as minimum standard.
Monitoring & Treatment Targets
HbA1c every 3 months until stable, then every 6 months. Individualised HbA1c target: 48–58 mmol/mol (6.5–7.5%) for most; less strict (64 mmol/mol, 8%) for frail/elderly/hypoglycaemia-prone. Annual: eGFR + uACR, lipids, blood pressure, foot examination, retinal screening, ECG.
Key Clinical Trials
Empagliflozin reduced CV death by 38% and HF hospitalisation by 35% in T2DM with established CVD vs placebo
Liraglutide reduced MACE by 13% vs placebo in T2DM with high CV risk (HR 0.87, p=0.01)
Clinical Guidelines
External Resources
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Frequently Asked Questions
What is the first-line treatment for type 2 diabetes in 2024?
ADA 2024 recommends lifestyle modification plus metformin as initial pharmacotherapy for most patients. However, if the patient has established cardiovascular disease, heart failure, or CKD, an SGLT2 inhibitor or GLP-1 receptor agonist with proven CV benefit should be added at diagnosis or early in treatment, regardless of HbA1c level.
What is the HbA1c target for type 2 diabetes?
ADA 2024 recommends an individualised HbA1c target: <48 mmol/mol (6.5%) for most patients if safely achievable; <53 mmol/mol (7%) for patients with established CVD or hypoglycaemia risk; up to 64 mmol/mol (8%) for elderly, frail, or patients with limited life expectancy. Time-in-range (TIR 70–180 mg/dL ≥70%) is now an equivalent target metric for CGM users.
When should SGLT2 inhibitors be used in type 2 diabetes?
SGLT2 inhibitors should be prioritised when there is established CVD, heart failure (any LVEF), or CKD — their cardiovascular and renal benefits are independent of blood glucose lowering. ADA 2024 recommends initiating an SGLT2 inhibitor in these patient groups regardless of current HbA1c or metformin use.
Medical disclaimer: This content is intended for qualified healthcare professionals and does not constitute medical advice. Always apply clinical judgment and refer to current local guidelines and institutional protocols.