AKT · Endocrine/Diabetes & glucose

Type 2 diabetes mellitus

Insulin resistance + relative insulin deficiency

Overview

Progressive insulin resistance with relative insulin deficiency, typically in older, overweight, inactive or high-risk-ethnicity patients. Often asymptomatic and found on screening; managed with lifestyle + a stepwise drug cascade anchored on metformin, with cardiovascular/renal protection from SGLT2 inhibitors and GLP-1 agonists. The exam tests the cascade and the contraindications.

Recognise

Often asymptomatic (found on screening) or insidious thirst, polyuria, fatigue, recurrent infections (thrush, UTIs)
Overweight/central adiposity, acanthosis nigricans, hypertension, dyslipidaemia (metabolic syndrome)
Complications may be the presentation: retinopathy, neuropathy (foot ulcer), nephropathy, CVD

Red flags

Hyperosmolar hyperglycaemic state (very high glucose, no ketones, dehydration, reduced consciousness) → emergency
Diabetic foot with ischaemia/infection/Charcot → urgent foot-protection team

Differentials & how to tell them apart

Type 1 diabeteslean, young, ketotic, antibody-positive, low C-peptide, insulin-dependent

Steroid-induced / pancreatic / endocrine diabetessecondary cause — steroids, chronic pancreatitis, Cushing's, acromegaly, haemochromatosis ('bronze diabetes')

MODYyoung, AD family history, antibody-negative

Investigations

HbA1c ≥48 mmol/mol (≥6.5%) or fasting glucose ≥7.0 or random ≥11.1 (repeat if asymptomatic). Annual: HbA1c, ACR, eGFR, lipids, BP, retinal screening, foot check.

Management

Lifestyle + metformin (add an SGLT2 inhibitor if CV/renal risk)

1Structured education (DESMOND) + lifestyle. Start metformin (titrate). Assess CV/renal risk: if established CVD, heart failure or QRISK high, add (or start) an SGLT2 inhibitor for cardiorenal protection. Individualise HbA1c target (48 on metformin alone, 53 if on a drug causing hypoglycaemia).Gate: Metformin is contraindicated/withheld in significant renal impairment (eGFR <30) and around iodinated contrast/acute illness (lactic acidosis risk); a sulfonylurea causes hypoglycaemia (DVLA, falls) so is not first choice when that matters
2HbA1c rises to ≥58 → intensify: dual then triple therapy (metformin + SGLT2/GLP-1/SU/DPP-4/pioglitazone), then injectable GLP-1 or insulin. Treat BP (ACE-i/ARB, esp. with albuminuria), statin, and annual complication screening.

Metformin — first-line (biguanide); weight-neutral, no hypoglycaemia; GI upset, withhold in AKI/contrast, B12 deficiency long-term

SGLT2 inhibitor (e.g. dapagliflozin/empagliflozin) — add (or first-line with metformin) if CVD/heart failure/CKD; glycosuria → genital thrush, euglycaemic DKA risk, volume depletion

GLP-1 receptor agonist (e.g. semaglutide) — weight loss + CV benefit; for obesity/when triple therapy fails; nausea, pancreatitis caution

Sulfonylurea (gliclazide) — effective, cheap, but causes HYPOGLYCAEMIA and weight gain

DPP-4 inhibitor (gliptin) / pioglitazone — weight-neutral / weight-gain+fluid; pioglitazone avoided in heart failure, bladder cancer, fracture risk

Key points

Metformin first (and an SGLT2 inhibitor early if the heart or kidneys are involved). The exam's favourite gates: metformin + eGFR<30/contrast, and sulfonylurea + hypoglycaemia. 'Bronze diabetes' = haemochromatosis; new diabetes + skin/acromegaly/Cushingoid features = a secondary cause.

Monitor & prognosis

HbA1c 3–6 monthly then 6-monthly; annual ACR/eGFR/retinal/foot/lipids/BP.

Largely modifiable; complications drive morbidity.

Source: NICE NG28 (T2DM); CKS Diabetes type 2