01Purpose and principlesWhat the treatment does and how it fits into care.
Diabetes medicine selection now addresses several outcomes at once. HbA1c describes longer-term glycaemic exposure, but it does not fully describe cardiovascular risk, kidney disease, hypoglycaemia or the burden of treatment. Two adults with the same HbA1c may therefore need different strategies. Someone with established atherosclerotic disease may benefit from an additional medicine selected partly for cardiovascular protection, while a frail person with poor intake may need simplification to prevent immediate harm. Begin by defining the diabetes type, current symptoms, kidney function, comorbidities and the person’s priorities. Do not apply a routine type 2 diabetes algorithm to an insulin-deficient emergency or assume that every episode of hyperglycaemia reflects ordinary progression.
The mechanisms explain many practical choices. Metformin reduces hepatic glucose production and has little intrinsic tendency to cause hypoglycaemia. SGLT2 inhibition increases urinary glucose loss and modifies renal sodium handling; its protective indications are not identical to its glucose-lowering capacity. GLP-1 receptor agonism affects glucose-dependent insulin responses and appetite, while sulfonylureas stimulate insulin secretion and can cause hypoglycaemia when meals are missed. Insulin can be essential for symptomatic or catabolic hyperglycaemia but requires an administration, monitoring and adjustment plan. Rather than accumulating medicines whenever a laboratory target is missed, check whether the intended treatment is taken, tolerated and suited to the dominant clinical problem.
Key points
- NICE NG28 changed in February 2026: initial treatment for many adults is modified-release metformin plus an SGLT2 inhibitor, with separate cardiovascular, renal and frailty branches.
- Introduce medicines stepwise: start metformin and establish its highest tolerated dose, then add the SGLT2 inhibitor without unnecessary delay. Choosing an initial combination does not require starting every drug on the same day.
- A selected metformin prolonged-release regimen starts at 500 mg orally once daily with the evening meal, increasing by 500 mg every 10–15 days to 2 g daily if appropriate; renal function limits the permitted dose.
- Dapagliflozin is usually 10 mg orally once daily. Its glucose-lowering effect falls below eGFR 45 mL/min/1.73 m², but eligible patients may retain cardiac or renal benefit; the current product does not recommend initiation below eGFR 15.
- Established atherosclerotic cardiovascular disease has a specific NICE initial option including subcutaneous semaglutide up to 1 mg weekly alongside metformin and an SGLT2 inhibitor, subject to suitability.
- Frailty changes the benefit–harm assessment: NICE advises SGLT2 treatment only when the level of frailty does not create unacceptable adverse-event risk, such as volume depletion or hypotension.
- SGLT2-associated ketoacidosis can occur with modest glucose. During hospitalisation for major surgery or serious acute illness, interrupt treatment, monitor blood ketones and restart only when ketones are normal and the clinical condition is stable.
02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.
Weight loss, ketosis, vomiting, dehydration and marked symptoms raise concern for an acute metabolic problem or a different diabetes classification. A prior type 2 label does not exclude insulin deficiency. Assess urgent illness before adding another routine oral medicine. If insulin is already prescribed, a sick-day review must not translate into indiscriminate cessation of all insulin.
Document atherosclerotic cardiovascular disease, heart failure, kidney function, albuminuria, early-onset disease, obesity and frailty. Current NG28 uses these features to refine initial treatment. They should be visible in the prescribing rationale, because a medicine selected for renal protection may remain useful even after its glucose effect diminishes.
Discuss meal pattern, work, driving, health literacy, injection confidence and medicine access. Ask about fasting and very low-carbohydrate diets before SGLT2 treatment. An apparently simple daily prescription can become unsafe if the person cannot recognise dehydration or has no practical way to obtain help when unwell.
Metformin gastrointestinal symptoms may improve with a slower increase, but severe vomiting or dehydration needs assessment. SGLT2 treatment can cause genital infection and volume depletion; abdominal pain, nausea or breathlessness raises ketoacidosis even without extreme glucose. New persistent severe abdominal pain during GLP-1 treatment needs urgent assessment for pancreatitis and other causes.
03Assessment before treatmentTests and checks that guide safe selection.
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 and a clinically relevant glucose profileFirst step - Why
- Assess longer-term response and patterns that inform adjustment.
- Interpretation and limitations
- HbA1c changes over weeks to months and should not be used as an immediate measure of a dose taken yesterday. Review home or sensor data when hypoglycaemia, insulin adjustment or symptom patterns require it. Consider whether altered red-cell turnover makes the HbA1c misleading before intensifying a regimen that already produces low glucose.
- 02
Kidney function and urinary albumin assessment - Why
- Select medicines and doses while assessing renal risk.
- Interpretation and limitations
- Use the renal measure specified by the individual product and the relevant NICE branch. Metformin dose limits and SGLT2 glucose efficacy are different questions. An acute deterioration during vomiting cannot be treated as if it were stable CKD simply because the current eGFR falls into a familiar chronic category.
- 03
Blood ketones and acid–base assessment when unwell - Why
- Investigate possible ketoacidosis even with modest glucose concentrations.
- Interpretation and limitations
- An SGLT2 user with nausea, abdominal pain or deep breathing needs urgent clinical assessment and blood ketone testing. Glucose alone may falsely reassure. Interpret ketones with acid–base status, hydration and the clinical history; routine outpatient dose escalation is inappropriate when an acute ketoacidotic process is possible.
- 04
Vitamin B12 when clinically indicated - Why
- Investigate anaemia or neuropathy and assess metformin-associated deficiency risk.
- Interpretation and limitations
- MHRA advises testing when deficiency is suspected and considering periodic monitoring in those with risk factors. New neuropathy should not automatically be attributed to diabetes. Treat confirmed deficiency and review its causes; metformin can often continue if tolerated and otherwise suitable while the deficiency is corrected.
04Treatment approachPreparation, options, escalation and aftercare.
01InitiationIntroduce a current initial type 2 regimenFirst stepAn adult has confirmed type 2 diabetes without an acute metabolic emergency.+
- 1Identify the relevant comorbidity and frailty pathway, agree an individual glycaemic goal and discuss the purpose of each proposed medicine. Check renal function, current symptoms, pregnancy plans and factors that increase ketoacidosis or dehydration risk.
- 2For an appropriate adult, begin modified-release metformin at a low dose with food and increase gradually within the selected product’s renal limits. Review gastrointestinal tolerability rather than assuming that the first episode of mild nausea requires permanent abandonment.
- 3Once the highest tolerated metformin dose is established, add the selected SGLT2 inhibitor without avoidable delay when indicated and suitable. Explain its protective purpose, genital symptoms, hydration and ketoacidosis warning signs before issuing the prescription.
- 4EscalationArrange follow-up that checks actual use, tolerability, laboratory safety and subsequent glycaemic response. Additional treatment for atherosclerotic disease or another branch needs its own introduction and counselling plan rather than an undocumented simultaneous escalation.
02Acute safetyAssess an unwell SGLT2 userA patient taking dapagliflozin develops vomiting, reduced intake or breathlessness.+
- 1Assess physiological stability, hydration, glucose and blood ketones promptly. Do not exclude ketoacidosis because glucose is only moderately raised; symptoms and acid–base disturbance may reveal a serious metabolic emergency.
- 2Withhold the SGLT2 inhibitor during the relevant acute illness and use the urgent diabetes or emergency pathway if ketoacidosis is suspected. Review metformin and other medicines that may be unsafe with dehydration, hypoxia or acute kidney injury.
- 3If insulin is prescribed, obtain an individual sick-day plan and specialist advice where needed; avoid a blanket instruction to stop every diabetes medicine. Ensure the person understands when inability to drink, persistent vomiting or worsening symptoms requires immediate help.
- 4Document the restart assessment. Following interruption for major surgery or serious illness, blood ketones should be normal and the clinical condition stable before SGLT2 treatment resumes; a confirmed DKA episode needs a separate specialist reconsideration of future suitability.
03ReviewSimplify treatment when harm outweighs benefitAn older adult with diabetes has recurrent low glucose, weight loss or increasing frailty.+
- 1Obtain actual glucose readings and identify which medicines can cause hypoglycaemia. Assess missed meals, kidney decline, administration errors and new dependence on carers before assuming that the prescribed dose is still appropriate.
- 2Revisit the individual glycaemic target and the purpose of each medicine. Reducing an insulin or sulfonylurea regimen may address immediate hypoglycaemia, while decisions about protective treatment also require consideration of frailty, blood pressure and volume status.
- 3Agree a specific change, an observation period and thresholds for seeking help. Ensure the person administering treatment has the revised prescription and understands what has stopped, what remains and when the effect will be reviewed.
- 4Check both reduced harm and preserved symptom control after simplification. A successful review may mean fewer hypoglycaemic episodes and a manageable regimen rather than pursuit of a numerically lower HbA1c.
05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.
Metformin hydrochloride prolonged-release tablets
Selected UK SmPC: 500 mg orally once daily with the evening meal; increase by 500 mg every 10–15 days if tolerated, usually to 2 g daily maximum. At GFR 30–44 mL/min, maximum 1 g daily; below 30, contraindicated.At GFR 45–59, assess lactic-acidosis risks and start no higher than half the 2 g maximum; at 30–44 start no higher than half the 1 g maximum. Hold for relevant acute dehydration or hypoxia; assess B12 and pregnancy-specific guidance.
Dapagliflozin
10 mg orally once daily for suitable adults; continue according to indication and regular benefit–risk review. The current Forxiga SmPC does not recommend starting below eGFR 15 mL/min/1.73 m².Glucose efficacy is reduced below eGFR 45. Severe hepatic impairment uses a 5 mg starting dose with potential increase to 10 mg. Avoid assuming suitability in pregnancy or insulin deficiency; manage dehydration and DKA risk explicitly.
Subcutaneous semaglutide for an eligible NG28 pathway
Ozempic starts at 0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg weekly; after at least 4 further weeks, increase to 1 mg weekly if required. The 2026 NG28 recommendation covers doses up to 1 mg weekly.The introductory dose is not maintenance. Higher licensed product doses are not automatically the NG28 recommendation. Assess retinopathy, gastrointestinal tolerance and pancreatitis symptoms; stop at least 2 months before planned pregnancy and review hypoglycaemia-causing co-treatment.
06Complications, monitoring and follow-upAdverse effects, response and longer-term review.
- Use early contact to assess tolerability and understanding, then repeat glycaemic assessment at a clinically appropriate interval. A medicine can be pharmacologically effective yet fail because the person stopped it without telling the prescribing team.
- Reassess renal function during acute illness and at an interval suited to the baseline trajectory. Write whether a change concerns metformin accumulation, SGLT2 glycaemic efficacy, cardiorenal eligibility or several of these issues.
- Ask about genital symptoms, dizziness, fasting plans and very low-carbohydrate diets at SGLT2 reviews. Practical anticipatory advice is more useful than expecting the patient to connect a future illness with a warning delivered only once.
- Review weight, hypoglycaemia and injection technique when adding GLP-1 therapy or adjusting insulin. Rapid glycaemic improvement and existing retinopathy require appropriate eye-care coordination, while reduced intake may necessitate review of hypoglycaemia-causing drugs.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
National selection and product licensing differ
NG28 identifies which strategy to offer to a patient group. The SmPC supplies product-specific dosing and restrictions. Dapagliflozin’s current initiation threshold does not mean every person above that threshold belongs in the same NICE initial-treatment branch.
A combination can be introduced sequentially
Stepwise introduction helps attribute adverse effects and find a tolerable metformin dose. It should not become a reason to leave an eligible person on metformin alone for months without reassessing the planned protective treatment.
Frailty is a prescribing variable
A person prone to hypotension and dehydration may face different SGLT2 risks from another adult of the same age. Assess function, intake and physiological reserve rather than using a birthday as the sole decision criterion.
Dose ceilings answer different questions
The semaglutide product licence and NICE’s particular 2026 recommendation are not identical in dose scope. Record the indication and pathway when interpreting a weekly prescription so that an available pen strength does not determine the treatment plan.
08Common pitfallsFrequent interpretation and management errors.
- 01
Repeating an older metformin-only initial algorithm without checking the February 2026 NG28 changes can omit currently recommended cardiorenal treatment.
- 02
Using a glucose reading that is not markedly raised to dismiss SGLT2-associated ketoacidosis can delay recognition of a serious acute illness.
- 03
Automatically stopping an SGLT2 inhibitor solely because its glucose effect falls with eGFR can overlook a continuing eligible protective indication.
- 04
Treating all GLP-1 products, oral formulations, weekly pens and doses as interchangeable can create a clinically important administration error.