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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.

Definition

Type 2 diabetes is a chronic metabolic disorder of hyperglycaemia caused by insulin resistance with progressive relative insulin deficiency and associated cardiovascular, renal, retinal, neurological and foot risk.

Epidemiology

Common and increasing with age, adiposity, inactivity, family history, previous gestational diabetes and some ethnic backgrounds. It can occur in younger adults and should not be excluded by age or BMI alone.

Pathophysiology

Insulin resistance increases hepatic glucose output and reduces peripheral glucose uptake. Beta cells initially compensate with hyperinsulinaemia, but progressive beta-cell dysfunction produces relative insulin deficiency and sustained hyperglycaemia. Residual insulin usually limits ketogenesis, while severe hyperglycaemia and osmotic diuresis can produce HHS. Chronic glycaemic, blood-pressure and lipid exposure damages small and large vessels.

First principles

Insulin resistance is followed by relative insulin deficiency

Muscle, liver and adipose tissue become less responsive to insulin, while pancreatic beta cells initially compensate by increasing secretion. Diabetes develops when beta-cell reserve no longer matches the metabolic demand. Residual insulin usually limits ketogenesis, but it does not prevent severe hyperglycaemia or hyperosmolar hyperglycaemic state.1,2

Osmotic symptoms are a consequence of glycosuria

Marked hyperglycaemia causes glucose to pass into urine and pull water with it, producing polyuria, thirst and dehydration. Many people remain asymptomatic and are diagnosed on screening or during assessment of a complication, so absence of osmotic symptoms does not mean absence of vascular risk.1,2

Cardiorenal protection is part of glucose-lowering selection

Retinopathy, kidney disease and neuropathy reflect small-vessel injury, while atherosclerotic cardiovascular disease and heart failure drive much of the morbidity and mortality. NICE therefore selects initial medicines by cardiovascular, renal, obesity, early-onset and frailty status as well as by HbA1c; the choice is not simply a glucose-lowering ladder.2,3,4

Insulin is eventually needed when endogenous reserve or treatment options are insufficient

Progressive beta-cell failure, acute metabolic decompensation or inability to use other agents may require insulin. It replaces deficient hormone action but adds hypoglycaemia and weight-gain risk, so initiation needs structured education, safe prescribing and a clear titration and sick-day plan.5,6

Presentation

Often asymptomatic and detected on screening or routine blood tests; symptomatic disease causes thirst, polyuria, fatigue, recurrent infection, blurred vision or weight loss. Acute dehydration, confusion or ketosis indicates metabolic decompensation rather than uncomplicated new type 2 diabetes.2,1,7,8

Cardinal features

  • Polyuria and polydipsia
  • Fatigue or lethargy
  • Blurred vision
  • Recurrent thrush or other infections
  • Unintentional weight loss with marked hyperglycaemia
  • Asymptomatic hyperglycaemia found on screening

Red flags

  • Vomiting, abdominal pain, deep or laboured breathing, or ketones suggesting diabetic ketoacidosis
  • Severe dehydration, confusion, drowsiness or reduced consciousness suggesting hyperosmolar hyperglycaemic state
  • Rapid weight loss, ketosis or abrupt deterioration: reconsider type 1, pancreatic or secondary diabetes
  • Foot ulceration, spreading infection, critical ischaemia or systemic sepsis
  • Acute visual symptoms or sight-threatening retinopathy

Investigations

HbA1c, or plasma glucose when HbA1c is unsuitable

Use HbA1c to diagnose type 2 diabetes when clinically appropriate and to monitor treatment. If symptoms are rapidly evolving, there is acute illness, or a condition may make HbA1c unreliable, use plasma glucose and assess for ketones and acidosis rather than delaying assessment for HbA1c.

Expected finding: HbA1c at or above 48 mmol/mol supports diabetes and should be confirmed on repeat if the person is asymptomatic; symptomatic or acutely unwell people need prompt plasma glucose assessment.

2,1

Blood or urine ketones and venous acid-base assessment when acutely unwell

Type 2 diabetes does not exclude diabetic ketoacidosis, particularly with rapid weight loss, infection, SGLT2 inhibitor exposure or insulin deficiency. Check ketones, venous pH or bicarbonate, glucose, U&E and clinical hydration when DKA or another hyperglycaemic emergency is possible.

Expected finding: Raised ketones with metabolic acidosis supports DKA; very high glucose with marked dehydration, altered cognition and raised osmolality supports HHS.

8,1,7,9

Urine albumin:creatinine ratio and eGFR

Measure albuminuria and renal function to detect diabetic kidney disease and select the current NICE medicine pathway. The eGFR bands above 30, 20 to 30 and below 20 have different recommendations for metformin, SGLT2 inhibitors and DPP-4 inhibitors.

Expected finding: Albuminuria may identify diabetic kidney disease even before eGFR falls; eGFR determines renal staging and medicine safety.

10,3,1

Blood pressure, full lipid profile and cardiovascular assessment

Assess blood pressure, smoking, BMI, renal function, lipids and established atherosclerotic cardiovascular disease or heart failure because these findings alter both diabetes medicine selection and preventive treatment. Use QRISK3 for adults aged 25 to 84 without established CVD, while recognising that risk tools are not appropriate for everyone at already high risk.

Expected finding: Hypertension, dyslipidaemia or established vascular disease commonly coexist and should be managed in parallel with hyperglycaemia.

4,11,3

Retinal, foot and annual diabetes-care assessment

Screen for retinopathy and foot risk and organise the nine key annual care processes, including HbA1c, blood pressure, cholesterol, smoking, body mass index, urine albumin, serum creatinine, foot surveillance and retinal screening. Complications can be silent until advanced.

Expected finding: Albuminuria, reduced eGFR, retinopathy, neuropathy, deformity, ulceration or cardiovascular risk may be identified and require a linked pathway.

10,12

Management

StepDetailSource
Recognise and escalate acute hyperglycaemic emergenciesTreat vomiting, abdominal pain, deep breathing, ketones, severe dehydration, confusion or reduced consciousness as possible DKA or HHS. Start ABCDE assessment, obtain glucose, ketones, venous blood gas, U&E, osmolality and fluid-balance data, look for a precipitant such as sepsis, foot infection, treatment omission, myocardial infarction or stroke, and arrange urgent hospital admission. Follow the current DKA or JBDS HHS pathway; involve senior, diabetes and critical-care teams when physiology or cognition is severely abnormal, and avoid rapid osmotic shifts.8,1,7NICE NG17, NICE CKS Diabetes type 2 and JBDS-IP HHS care pathway in adults
Confirm the diagnosis, classify safely and provide structured educationUse the clinical presentation and HbA1c or plasma glucose appropriately; do not let age, BMI or a presumed type 2 phenotype overrule ketosis, rapid weight loss or abrupt deterioration. Consider type 1, LADA, pancreatic, monogenic, steroid-induced and other secondary diabetes when the course is atypical. Offer structured education, dietary and physical-activity advice, smoking cessation support, weight-management support and an individualised self-management plan.2,1,13NICE NG28 and NICE CKS Diabetes type 2
Choose initial medicines by comorbidityIntroduce medicines stepwise, starting with modified-release metformin and checking tolerability. For most adults, including those with no relevant comorbidity, obesity, heart failure or CKD with eGFR above 30, offer modified-release metformin plus an SGLT2 inhibitor; if metformin is contraindicated or not tolerated, offer SGLT2 inhibitor monotherapy. For established atherosclerotic cardiovascular disease, offer modified-release metformin, an SGLT2 inhibitor and subcutaneous semaglutide up to 1 mg once weekly. For early-onset type 2 diabetes, consider a GLP-1 receptor agonist or tirzepatide when further medicines are needed. For CKD with eGFR 20 to 30, offer dapagliflozin or empagliflozin plus a DPP-4 inhibitor; below eGFR 20, consider a DPP-4 inhibitor. In frailty, prioritise symptom control and minimise medicines; use an SGLT2 inhibitor only when volume depletion or hypotension risk is acceptable.3,2,14,15NICE NG28 initial medicines, February 2026 update
Set and review an individualised HbA1c targetSupport an HbA1c target of 48 mmol/mol (6.5%) when the initial medication regimen is not associated with hypoglycaemia, and 53 mmol/mol (7.0%) when treatment is associated with hypoglycaemia, such as a sulfonylurea or insulin. If HbA1c rises to 58 mmol/mol (7.5%), reinforce healthy living and adherence and intensify treatment. Consider a less stringent target through shared decision-making for older or frail people, limited life expectancy or substantial hypoglycaemia risk.16,1NICE NG28 blood glucose management
Add further treatment without unsafe combinationsBefore changing therapy, optimise adherence, dosing, formulation and non-pharmacological care. For most people who need further glucose lowering, add a DPP-4 inhibitor; if it is contraindicated, not tolerated or ineffective, add a sulfonylurea, pioglitazone or insulin-based treatment according to the person's circumstances. In heart failure avoid pioglitazone; in CKD follow the eGFR-specific pathway and use a sulfonylurea only when eGFR is above 30. In established atherosclerotic cardiovascular disease, add semaglutide up to 1 mg weekly if it was not already used initially. Do not combine a DPP-4 inhibitor with a GLP-1 receptor agonist or tirzepatide. For obesity, a GLP-1 receptor agonist or tirzepatide may be considered after at least 3 months of initial therapy when further glycaemic treatment is needed; use the obesity guideline if weight loss is the primary aim.17,3,13,18NICE NG28 further medication and prescribing guide
Start insulin safely when indicatedConsider insulin for acute hyperglycaemia, persistent worsening despite appropriate non-insulin therapy or when other medicines are unsuitable. Provide structured education covering injection technique and site rotation, self-monitoring, titration, diet, hypoglycaemia, acute glucose changes and DVLA advice. Continue metformin if already taking it and stop medicines used solely for hyperglycaemia; discuss whether to continue medicines used for cardiovascular or weight benefit. Offer basal insulin once or twice daily initially; especially when HbA1c is 75 mmol/mol (9.0%) or higher, consider basal plus short/rapid-acting insulin or a premixed preparation. Check current product availability and BNF/local specialist advice because insulin products may be withdrawn or in shortage.5,6,19NICE NG28 insulin-based treatments and BNF insulin treatment summaries
Give SGLT2 inhibitor sick-day and DKA safety adviceExplain DKA symptoms and risk factors, including acute illness, dehydration, reduced food intake, surgery and insulin deficiency. Interrupt an SGLT2 inhibitor during hospitalisation for major surgery or acute serious medical illness and do not restart until the condition has stabilised; follow local perioperative advice. Ensure the person knows when to seek urgent assessment, and monitor blood ketones in hospital during an interruption. Do not assume a normal or only modest glucose excludes SGLT2-associated DKA.9,20,21,14,15MHRA Drug Safety Update on SGLT2 inhibitors and NICE NG28 medicines safety
Treat cardiovascular and renal risk in parallelMeasure blood pressure at least annually when there is no diagnosed hypertension or renal disease, and manage hypertension using the current NICE pathway. For primary CVD prevention, offer atorvastatin 20 mg when QRISK3 is 10% or more after informed discussion; do not rule it out below 10% when the person prefers treatment or risk may be underestimated. For established CVD, offer atorvastatin 80 mg unless a lower dose is appropriate because of interactions, adverse-effect risk or preference. Statins are contraindicated in pregnancy and should be stopped when pregnancy is possible.11,4NICE NG136 and NICE NG238
Complete ongoing complication surveillance and follow-upReview HbA1c, hypoglycaemia risk, blood pressure, lipids, smoking, BMI, renal function and urine albumin at the appropriate intervals, and ensure annual retinal screening and foot assessment. Arrange prompt foot-pathway referral for ulceration, infection, gangrene, suspected critical ischaemia or unexplained hot swollen foot. Reassess medicines at every review, continuing agents for cardiorenal benefit when appropriate even if their glucose-lowering effect is limited, and stop ineffective or harmful treatment collaboratively.10,12,22,23NICE NG28 complications, NICE QS209 and NICE NG19
Plan pregnancy, frailty and specialist review explicitlyDiscuss pregnancy intentions and refer for preconception or antenatal diabetes care rather than applying the routine pathway unchanged. In frailty, prioritise symptom control, individualise targets and minimise treatment burden because hypoglycaemia, falls, volume depletion and hypotension may cause more harm. Seek specialist input for diagnostic uncertainty, recurrent DKA or HHS, severe hypoglycaemia, complex CKD, rapid deterioration, pregnancy, difficult foot disease or failure to meet targets despite an optimised plan.3,24,1NICE NG28, NICE NG3 and NICE CKS Diabetes type 2

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

Differentials

Type 1 diabetes or LADA

Rapid progression, weight loss, ketosis or insulin deficiency; use specialist classification testing when the course is atypical.

Secondary diabetes

Steroid or medicine exposure, pancreatic disease, endocrinopathy or another secondary cause.

Monogenic diabetes

Young onset, non-obese phenotype and a strong multigenerational family pattern.

Stress hyperglycaemia

Hyperglycaemia during acute illness that does not persist as diabetes after recovery.

Hyperosmolar hyperglycaemic state

Severe hyperglycaemia, dehydration, raised osmolality and altered cognition requiring emergency management.

Complications

  • Atherosclerotic cardiovascular disease, heart failure and peripheral arterial disease
  • Diabetic kidney disease and albuminuria
  • Retinopathy and visual loss
  • Peripheral and autonomic neuropathy
  • Diabetic foot ulceration, infection and amputation
  • Hypoglycaemia from sulfonylureas or insulin
  • Diabetic ketoacidosis and hyperosmolar hyperglycaemic state

Prognosis

Prognosis is determined by duration and control of hyperglycaemia, blood pressure, lipids, smoking, renal disease, obesity and established cardiovascular disease. Early cardiorenal-risk reduction and reliable complication surveillance reduce avoidable morbidity.

Guidelines

  • Type 2 diabetes in adults: management (NG28) (NICE, 2026)
  • Cardiovascular disease: risk assessment and reduction, including lipid modification (NG238) (NICE, 2023)
  • Hypertension in adults: diagnosis and management (NG136) (NICE, 2026)
  • Diabetic foot problems: prevention and management (NG19) (NICE, 2015)
  • HHS care pathway in adults (JBDS 06) (JBDS-IP, 2022)

References

  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

Evidence checked: 2026-08-03

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.