Type 2 diabetes mellitus

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Type 2 diabetes develops through varying combinations of insulin resistance, impaired beta-cell secretion, altered incretin physiology and excess hepatic glucose production. It is strongly associated with obesity in many people but also occurs at lower body mass, and the label should be reconsidered when onset, ketones, family pattern or treatment response is atypical. At diagnosis, assess symptoms, ketones when indicated, blood pressure, weight, renal function, urine albumin-creatinine ratio, lipids, smoking, feet and eye-screening eligibility. Explore cardiovascular disease, heart failure and kidney disease because these diagnoses now drive medicine choice independently of glucose lowering. Discuss nutrition, movement, sleep, alcohol, mental health and socioeconomic barriers without implying that diabetes is a moral failure.

NICE NG28 was updated in 2026 and its live recommendation tables and visual summary should govern prescribing. For many adults, modified-release metformin plus an SGLT2 inhibitor is the initial pharmacological approach, subject to renal function, tolerability, frailty, ketoacidosis risk and shared choice. Established atherosclerotic cardiovascular disease, heart failure and chronic kidney disease lead to specific cardiorenal pathways, and some patients need GLP-1 receptor agonist-based treatment, other oral agents or insulin as therapy progresses. Every medicine decision should declare its aim: glucose reduction, protection of heart or kidney, weight benefit, symptom relief or avoidance of hypoglycaemia. Monitor response and discontinue ineffective or unsafe treatment rather than layering drugs indefinitely. Bariatric or metabolic surgery and intensive weight programmes may be appropriate through commissioned services. Diabetes remission is a valuable outcome, but ongoing HbA1c and complication surveillance remain important because relapse and legacy risk persist.

Key points

Type 2 diabetes is heterogeneous insulin resistance and beta-cell dysfunction; management should address cardiovascular, renal, metabolic and psychosocial risk rather than chase HbA1c alone.
At diagnosis, provide structured education, nutritional and activity support, smoking intervention and complication assessment alongside medicine discussion.
The current NICE NG28 pathway generally places modified-release metformin with an SGLT2 inhibitor at first line, with selection refined by established cardiovascular disease, heart failure, chronic kidney disease, frailty and contraindications.
Follow the current NICE visual summary and local formulary because cardiorenal pathways, licences, renal thresholds and cost-effective choices evolve faster than memory-based sequences.
Symptomatic marked hyperglycaemia or catabolism may require insulin or a sulfonylurea initially; review the need once glucose toxicity and the acute situation improve.
SGLT2 users need explicit ketoacidosis and sick-day education, including temporary interruption during major illness, fasting or surgery under the applicable pathway.
Set an individual HbA1c target that considers hypoglycaemia, frailty, comorbidity and preference, and intensify without therapeutic inertia when benefit outweighs burden.
Annual review integrates eyes, feet, kidneys, blood pressure, lipids, liver and cardiovascular status; remission does not erase surveillance or relapse risk.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Insulin resistance

Genetic susceptibility, adiposity, inactivity, sleep and environmental factors reduce insulin effectiveness in liver, muscle and adipose tissue.

Progressive beta-cell dysfunction

Pancreatic insulin secretion becomes insufficient for the degree of resistance and commonly declines as the condition progresses.

Hepatic and incretin dysregulation

Excess hepatic glucose production and altered gut-pancreas signalling contribute alongside resistance rather than one pathway explaining every patient.

Medicine and illness effects

Glucocorticoids, acute illness and some endocrine disorders can reveal or worsen hyperglycaemia in a susceptible person.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Insulin action becomes inefficient
Muscle takes up less glucose and adipose tissue releases more fatty acids, while the liver continues glucose production despite feeding.
2
Beta cells compensate
Pancreatic insulin secretion initially rises to offset resistance, but this compensation becomes inadequate as susceptible beta-cell reserve progressively declines.
3
Compensation fails
Insulin output no longer matches resistance, producing post-meal and then sustained hyperglycaemia with osmotic symptoms when more severe.
4
Vascular injury accumulates
Hyperglycaemia, hypertension, dyslipidaemia, inflammation and kidney disease combine to damage small and large blood vessels as the process continues.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical stable presentation

Gradual hyperglycaemia found through risk assessment, osmotic symptoms or recurrent infection without ketones is compatible with type 2 diabetes, but classification remains a probability rather than a visual diagnosis.

Glucose toxicity

Marked symptomatic hyperglycaemia, weight loss, dehydration and blurred vision can suppress beta-cell function transiently; short-term insulin may restore metabolic control while long-term needs are reassessed.

Cardiorenal priority

Atherosclerotic cardiovascular disease, heart failure, reduced eGFR or albuminuria changes treatment choice even if HbA1c is near target because some therapies provide outcome benefits beyond glycaemia.

Frailty and treatment harm

Falls, cognitive impairment, irregular meals, renal decline and limited life expectancy increase harm from hypoglycaemia and complex regimens, supporting simplified treatment and less stringent targets.

Misclassified diabetes

Ketosis, rapid insulin dependence, autoimmune features, onset at a young age, preserved C-peptide with a dominant family pattern or pancreatic disease should prompt type 1, monogenic or pancreatogenic assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
HbA1c with glucose reviewFirst step
Why
Measure chronic glycaemic exposure and support target setting when red-cell conditions make HbA1c reliable.
Interpretation and limitations
Assess change against the individual target and symptoms. Major discordance with capillary or sensor data requires investigation of anaemia, haemoglobinopathy, renal disease or rapid glucose change.
02
eGFR and urine albumin-creatinine ratio
Why
Detect diabetic kidney disease, stage renal risk and determine safe or beneficial medicine choices.
Interpretation and limitations
Confirm persistent albuminuria outside transient causes. eGFR and albuminuria together determine CKD risk, SGLT2 eligibility, renin-angiotensin treatment and nephrology thresholds.
03
Blood pressure and lipid profile
Why
Quantify major modifiable cardiovascular risks that often outweigh the incremental risk from a small HbA1c change.
Interpretation and limitations
Use current NICE cardiovascular and diabetes targets, comorbidity and tolerability to select antihypertensive and lipid-lowering treatment rather than treating glucose in isolation.
04
Foot risk assessment
Why
Identify neuropathy, ischaemia, deformity, callus, previous ulcer and active disease before tissue loss occurs.
Interpretation and limitations
Risk category determines review frequency. Ulceration, infection, gangrene, critical ischaemia or acute Charcot suspicion requires rapid multidisciplinary foot referral.
05
Retinal screening
Why
Detect diabetic retinopathy through the national screening pathway before visual symptoms develop.
Interpretation and limitations
Screening grade determines recall or ophthalmology referral. Sudden visual loss is not a routine screening issue and needs urgent clinical assessment.
06
Ketones and venous blood gas
Why
Exclude DKA in an unwell, catabolic or SGLT2-treated person even when type 2 diabetes is recorded.
Interpretation and limitations
Raised ketones with acidosis activates DKA care and should prompt later review of medicine contribution and diabetes classification.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Type 1 diabetes

Ketones, catabolic symptoms, autoimmune markers and rapid insulin dependence suggest autoimmune deficiency requiring prompt insulin rather than phenotype-based reassurance.

Monogenic diabetes

Young onset, a dominant multigenerational pattern, retained C-peptide and negative antibodies suggest a single-gene cause when combined with the history and other findings.

Pancreatic diabetes

Pancreatitis, pancreatic surgery, malabsorption or structural disease indicates endocrine loss associated with exocrine pancreatic pathology when supported by the history and examination.

Stress or steroid hyperglycaemia

Acute illness or glucocorticoid exposure can produce temporary elevation; follow-up after the trigger clarifies persistent diabetes.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01FoundationStart integrated treatmentFirst stepType 2 diabetes is newly confirmed and there is no metabolic emergency.

1Assess symptoms, renal function, albuminuria, cardiovascular and heart-failure history, frailty, pregnancy potential, complications and the person's priorities.
2First lineOffer structured education and tailored nutrition, activity and weight support, then select first-line medicines from the current NICE NG28 visual pathway and local formulary.
3Agree the aim and review point for each intervention, teach sick-day safety, arrange retinal and foot pathways, and address blood pressure, lipids and smoking concurrently.

02EscalateRespond when target is not metEscalationHbA1c remains above the agreed goal or symptoms persist after adequate trial, adherence support and tolerability review.

1Confirm that the result is valid and explore medicine access, adverse effects, injection concerns, diet, distress and steroid or illness effects before labelling treatment failure.
2Choose the next class using current comorbidity-specific NICE recommendations, renal function, weight preference, hypoglycaemia risk and the explicit outcome sought.
3Review efficacy and harm after the expected interval, intensify or simplify deliberately, and refer for specialist support when insulin, complex comorbidity or diagnostic uncertainty warrants.

03Acute safetyManage illness and proceduresA treated person develops vomiting, dehydration, reduced intake, major infection, fasting or planned surgery.

1Follow the written local sick-day or perioperative plan, checking glucose and ketones more often and maintaining safe hydration where possible.
2Temporarily interrupt SGLT2 inhibitors and other medicines unsafe with dehydration, hypoxia or acute kidney injury according to current guidance, with a clear restart decision.
3Seek urgent assessment for ketones, persistent vomiting, breathlessness, drowsiness or inability to drink, and use insulin-based emergency treatment when DKA or HHS criteria are present.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

Reduces hepatic glucose output with low intrinsic hypoglycaemia risk and remains a core glucose-lowering treatment in the current NICE pathway.

Modified-release metformin

Start at the locally recommended low oral dose with food and increase gradually to the tolerated effective regimen, adapting or stopping according to renal function and acute-illness guidance.

Gastrointestinal effects and vitamin B12 deficiency occur. Avoid when severe renal or hypoxic illness raises lactic-acidosis risk, and apply current contrast, surgery and sick-day rules rather than a blanket permanent stop.

Promotes urinary glucose and sodium loss and can provide heart-failure and kidney protection in eligible people beyond its glucose effect.

SGLT2 inhibitor

Use the licensed once-daily preparation selected by the current NICE indication, eGFR, comorbidity and local formulary, with renal review before initiation and during significant illness.

Discuss genital infection, volume depletion and euglycaemic DKA. Pause for major illness, fasting or surgery under the agreed pathway; recurrent ketosis, very low carbohydrate intake or severe insulin deficiency may make treatment unsuitable.

Improves glucose-dependent insulin response, reduces appetite and can deliver weight and cardiovascular benefit for selected adults.

GLP-1 receptor agonist

Start the guideline-selected subcutaneous or oral product at its licensed introductory regimen and titrate only as tolerated within current NICE eligibility and local commissioning criteria.

Nausea, vomiting and gallbladder disease can occur; dehydration may worsen kidney function. Follow current advice for pancreatitis symptoms, retinopathy risk with rapid improvement, pregnancy and peri-procedural aspiration concerns.

Stimulates endogenous insulin secretion and can reduce symptomatic hyperglycaemia quickly when a low-cost oral option is appropriate.

Sulfonylurea

Start the chosen oral agent conservatively and titrate against glucose and meal pattern, using lower exposure in renal impairment, older age or other hypoglycaemia risk.

Hypoglycaemia and weight gain are important; missed meals, alcohol and renal decline increase risk. Provide driving advice and reconsider ongoing need after temporary treatment for glucose toxicity.

Corrects progressive insulin deficiency and relieves catabolic or symptomatic hyperglycaemia when non-insulin treatment is insufficient or inappropriate.

Basal insulin

Initiate with a specialist- or locally agreed individual starting regimen and titration algorithm based on fasting glucose, hypoglycaemia risk, renal function and concurrent medicines.

Teach injection, monitoring, hypoglycaemia treatment, driving obligations and sick-day care before initiation. Review agents that raise hypoglycaemia risk and avoid over-basalisation when post-meal glucose is the main problem.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cardiovascular and heart failure disease

Atherosclerosis, hypertension, kidney disease and metabolic stress increase myocardial infarction, stroke, peripheral arterial disease and heart-failure risk.

Diabetic kidney disease

Glomerular metabolic and haemodynamic injury causes albuminuria and declining filtration, while amplifying cardiovascular, electrolyte and medicine-related risk.

Retinopathy and neuropathy

Chronic microvascular injury damages retina and peripheral or autonomic nerves, threatening vision, sensation, organ function and foot integrity.

Hyperosmolar decompensation

Severe relative insulin deficiency with inadequate water access can cause profound hyperglycaemia, dehydration, hypertonicity and neurological dysfunction.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Measure HbA1c every three to six months while therapy or targets are changing, then at an appropriate longer interval when stable, accounting for conditions that invalidate it.
Review eGFR and urine albumin-creatinine ratio at least annually and more often after progression, acute kidney injury or medicines that depend on renal function.
Complete annual foot risk assessment and retinal screening, with urgent pathways for active foot disease or acute visual symptoms.
Track blood pressure, lipids, smoking, weight and cardiovascular or heart-failure symptoms alongside glucose measures.
At each medicine review, record the intended cardiorenal, weight or glycaemic benefit, adverse effects, adherence and whether continuation remains justified.
After remission-level glycaemia without glucose-lowering medicines, continue periodic HbA1c and complication surveillance because recurrence and vascular risk remain.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Comorbidity can outrank HbA1c

An SGLT2 inhibitor may be valuable for heart or kidney outcomes even when additional glucose lowering is modest. State the protective aim so benefit is not judged only by HbA1c.

Glucose toxicity can reverse

Severe hyperglycaemia temporarily impairs beta-cell function. Insulin used at presentation need not always be permanent, but withdrawal should be planned and monitored rather than assumed.

Remission needs surveillance

Sustained glucose below the diabetic range without medicines is meaningful, yet prior exposure and relapse risk remain. Retinal, renal and cardiovascular follow-up should not vanish.

SGLT2 changes the DKA clue

Urinary glucose loss can keep plasma glucose deceptively modest while ketogenesis progresses. Symptoms plus ketones and pH matter more than an expected hyperglycaemic threshold.

A target is a negotiated safety tool

Tighter HbA1c is not automatically better in frailty or recurrent hypoglycaemia. The useful target balances future benefit, present harm and treatment burden.

11Common pitfallsFrequent interpretation and management errors.

01
Following an obsolete linear medicine ladder without checking the current NICE comorbidity-specific visual summary.
02
Intensifying glucose therapy while ignoring untreated albuminuria, hypertension, smoking or established cardiovascular disease.
03
Continuing an SGLT2 inhibitor through major fasting, dehydration or suspected ketoacidosis without applying sick-day guidance.
04
Assuming type 2 diabetes explains ketosis without reconsidering type 1, ketosis-prone or pancreatic diabetes.
05
Using a stringent HbA1c goal in a frail person with recurrent severe hypoglycaemia and irregular meals.
06
Removing all follow-up after remission and missing relapse or established microvascular risk.