PassFinals
Endocrinology & Metabolic

Type 2 Diabetes Mellitus

Progressive hyperglycaemia caused by insulin resistance with relative beta-cell failure; safe care treats acute metabolic decompensation, cardiorenal risk and complications as well as glucose.

In a nutshell

Insulin resistance with progressive beta-cell failure causes hyperglycaemia, often silently. First exclude DKA or HHS, then use the current NICE comorbidity-stratified medicine pathway, individualise HbA1c targets, protect the heart and kidneys, and complete annual complication care.

Classic presentation

Often an incidental HbA1c finding; otherwise thirst, polyuria, fatigue, blurred vision, recurrent infection or weight loss. Ketosis, vomiting, severe dehydration or altered consciousness is an emergency and should trigger reconsideration of the diabetes type.

Key points

  • Type 2 diabetes is insulin resistance plus progressive relative insulin deficiency; residual insulin does not make DKA impossible.
  • Diagnose with HbA1c when appropriate, but use plasma glucose, ketones and acid-base assessment when the presentation is rapidly evolving or acutely unwell.
  • NICE NG28 now starts modified-release metformin plus an SGLT2 inhibitor for most adults, introduced sequentially; the pathway changes with ASCVD, heart failure, CKD, obesity, early-onset disease and frailty.
  • The eGFR 20 to 30 pathway is not the same as the eGFR above 30 pathway: follow the current NICE bands rather than applying a blanket SGLT2 rule.
  • Individualise HbA1c targets according to hypoglycaemia risk, frailty, life expectancy and treatment regimen, then intensify when the target is no longer met.
  • Never combine a DPP-4 inhibitor with a GLP-1 receptor agonist or tirzepatide.
  • SGLT2 inhibitors have DKA safety rules: interruption during major surgery or acute serious illness, blood-ketone monitoring in hospital and urgent review for symptoms even without extreme hyperglycaemia.
  • Treat blood pressure, lipids, smoking, renal risk, feet and retinopathy in parallel; glucose control alone is not comprehensive diabetes care.

First-line investigation

HbA1c when reliable, with glucose and ketones or venous acid-base assessment if acutely unwell; stage renal, cardiovascular, retinal and foot risk at the same assessment.

Management

Exclude DKA and HHS first

  • Vomiting, abdominal pain, deep breathing, ketones, severe dehydration, confusion or reduced consciousness needs urgent assessment for DKA or HHS, ABCDE care, emergency blood tests, precipitant search and hospital admission through the relevant pathway.8,1,7

Confirm, educate and select the pathway

  • Use HbA1c when appropriate, but do not delay plasma glucose and ketone assessment in rapidly evolving illness. Offer structured education, dietary and activity advice, smoking cessation support and an individualised self-management plan.2,1,13
  • Assess ASCVD, heart failure, CKD and eGFR, obesity, early-onset disease and frailty before choosing medicines; current NICE pathways are comorbidity-specific.3,4,11

Start current NICE initial therapy

  • For most adults, offer modified-release metformin plus an SGLT2 inhibitor, introducing medicines stepwise and checking tolerability. If metformin is contraindicated or not tolerated, offer SGLT2 inhibitor monotherapy when appropriate.3,14,15
  • Established ASCVD uses modified-release metformin, an SGLT2 inhibitor and subcutaneous semaglutide up to 1 mg once weekly. CKD with eGFR 20 to 30 uses dapagliflozin or empagliflozin plus a DPP-4 inhibitor; below eGFR 20, consider a DPP-4 inhibitor. Frailty requires symptom-focused, low-burden prescribing and caution with volume depletion or hypotension.3,17,14,15

Individualise targets and add treatment safely

  • Aim for HbA1c 48 mmol/mol (6.5%) with a regimen not associated with hypoglycaemia and 53 mmol/mol (7.0%) when treatment is associated with hypoglycaemia; at 58 mmol/mol (7.5%), reinforce lifestyle and adherence and intensify treatment. Relax targets case by case when risks outweigh benefits.16
  • For further glucose lowering, add a DPP-4 inhibitor for most people; if unsuitable or ineffective, consider a sulfonylurea, pioglitazone or insulin according to comorbidity. Do not combine a DPP-4 inhibitor with a GLP-1 receptor agonist or tirzepatide; avoid pioglitazone in heart failure.17,18
  • Offer basal insulin once or twice daily initially when insulin is needed; especially with HbA1c 75 mmol/mol (9.0%) or higher, consider adding short or rapid-acting insulin or using a premixed regimen. Provide structured education and continue metformin when already prescribed.5,6,19

Prevent medicine-related harm

  • Give SGLT2 sick-day advice: explain DKA symptoms and risk factors, interrupt treatment during major surgery or acute serious illness, monitor blood ketones in hospital and do not restart until the acute condition has stabilised. Normal or modest glucose does not exclude SGLT2-associated DKA.9,20,21,14,15
  • Treat blood pressure, lipids, smoking, weight and renal risk in parallel. For primary prevention, offer atorvastatin 20 mg when QRISK3 is 10% or more after informed discussion; for established CVD, offer atorvastatin 80 mg unless a lower dose is appropriate.4,11

Complete annual diabetes care

  • Review glycaemia, hypoglycaemia risk, blood pressure, lipids, smoking, BMI, urine albumin, eGFR, foot risk and retinal screening, and ensure the nine key annual care processes are completed. Refer urgently for ulceration, infection, gangrene, critical ischaemia or an unexplained hot swollen foot.10,12,22
  • Reassess medicine benefit, safety and treatment burden at every review; continue cardiorenal-benefit therapy when appropriate even if glucose lowering is limited, and refer for specialist help with diagnostic uncertainty, recurrent emergencies, complex CKD, pregnancy or failure of an optimised plan.23,3,24,1

Exam traps

  • A presumed type 2 phenotype does not exclude DKA, especially with rapid weight loss, infection, SGLT2 exposure or insulin deficiency.
  • Obesity does not make a GLP-1 receptor agonist or tirzepatide universally first-line: current NICE initial treatment is modified-release metformin plus an SGLT2 inhibitor, with later options stratified by indication.
  • Do not use a single eGFR threshold for every medicine: current NICE recommendations distinguish eGFR above 30, 20 to 30 and below 20.
  • Do not combine a DPP-4 inhibitor with a GLP-1 receptor agonist or tirzepatide.
  • Do not continue an SGLT2 inhibitor through major surgery or acute serious illness without following the interruption and ketone-monitoring safety pathway.
  • Pioglitazone is inappropriate in heart failure; sulfonylureas and insulin increase hypoglycaemia risk.

Illustrations

Insulin resistance and beta-cell declineGraph illustrating compensatory hyperinsulinaemia maintaining near-normal glycaemia until progressive beta-cell failure allows glucose to rise.PassFinals · original
Diabetic retinopathy fundoscopyRetinal photograph showing microaneurysms, dot-and-blot haemorrhages and exudates of background diabetic retinopathy.Shaofeng Hao, Changyan Liu, Na Li, Yanrong Wu, Dongdong Li, Qingyue Ga, Wikimedia Commons · CC-BY-4.0
Neuropathic diabetic foot ulcer assessmentPhotograph demonstrating assessment of foot sensation, pulses and pressure areas at risk of ulceration.Dayya D, O'Neill OJ, Huedo-Medina TB, Habib N, Moore J, Iyer K, Wikimedia Commons · CC-BY-4.0

Key sources

  1. NICE CKS, Diabetes type 2
  2. NICE, Type 2 diabetes in adults: management (NG28)Published 2 Dec 2015 | Updated 18 Feb 2026
  3. NICE NG28, initial medicines (NG28 recommendations 1.13 to 1.19)Updated 18 Feb 2026
  4. NICE, Cardiovascular disease: risk assessment and reduction, including lipid modification (NG238)Published 14 Dec 2023
  5. NICE NG28, insulin-based treatments (NG28 recommendations 1.32 to 1.37)Updated 18 Feb 2026
  6. BNF, Insulin treatment summaries
  7. JBDS-IP, HHS care pathway in adults (JBDS 06)Published 1 Jan 2022
  8. NICE, Type 1 diabetes in adults: diagnosis and management, ketone and DKA recommendations (NG17)Published 26 Aug 2015 | Updated 17 Aug 2022
  9. MHRA, SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis (Drug Safety Update April 2016)Published 18 Apr 2016
  10. NICE NG28, complications and cardiovascular risk (NG28 complications recommendations)Updated 18 Feb 2026
  11. NICE, Hypertension in adults: diagnosis and management (NG136)Published 28 Aug 2019 | Updated 26 Feb 2026
  12. NICE, Diabetes in adults quality standard (QS209)Updated 18 Feb 2026
  13. NICE, Overweight and obesity management (NG246)Published 14 Jan 2025
  14. BNF, Dapagliflozin
  15. BNF, Empagliflozin
  16. NICE NG28, blood glucose management (NG28 recommendations 1.5.7 to 1.5.9)Updated 18 Feb 2026
  17. NICE NG28, further medication (NG28 recommendations 1.25 to 1.31)Updated 18 Feb 2026
  18. BNF, Pioglitazone
  19. DVLA, Diabetes mellitus: assessing fitness to driveUpdated 7 Nov 2025
  20. MHRA, SGLT2 inhibitors: monitor ketones in blood during treatment interruption for surgery or acute serious illness (Drug Safety Update March 2020)Published 18 Mar 2020
  21. NICE NG28, medicines safety (NG28 medicines safety resource)Updated 18 Feb 2026
  22. NICE, Diabetic foot problems: prevention and management (NG19)Published 26 Aug 2015
  23. NICE NG28, reviewing medicines (NG28 reviewing medicines resource)Updated 18 Feb 2026
  24. NICE, Diabetes in pregnancy: management from preconception to the postnatal period (NG3)Published 25 Feb 2015 | Updated 16 Dec 2020

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.