Guideline in a nutshell: Game-changing update to NICE guideline on type 2 diabetes

The final, updated guidance from NICE signals a sea-change from previous guidelines by confirming SGLT2 inhibitors as first-line therapies for the management of type 2 diabetes .

The guideline update moves away from NICE’s previous 'one-size-fits-all' approach, shifting from automatically starting everyone on one medicine (usually metformin) to personalised treatment plans that aim to prevent cardiovascular and renal disease.¹

In line with the 10-Year Health Plan for the NHS,² the guideline re-sets clinical priorities from treatment to prevention, through an approach designed to prevent the future complications of diabetes.

Significantly, the changes also bring NICE guidelines into closer alignment with guidance from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).³

NICE’s guideline development committee (GDC) has expanded access to SGLT2 inhibitors (such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) from being second-line drugs to first-line treatment, even for people with type 2 diabetes and no significant comorbidities.

The GDC says: ‘There is a significant body of evidence showing that type 2 diabetes management should aim at holistic health improvements (in particular, cardiovascular and renal protection), rather than just HbA1c targets.’

The final version of the guideline update also highlights current inequalities in the use of SGLT2 inhibitors, and recommends that healthcare professions should:

• Monitor who is using SGLT2 inhibitors
• Identify patients who are eligible but not being prescribed SGLT2 inhibitors
• Encouraging them to use SGLT2 inhibitors

Comparisons of antidiabetic therapies have demonstrated that therapy combining metformin with an SGLT2 inhibitor was more clinically effective at reducing cardiovascular events than metformin alone or any other regimen combining metformin with one other diabetes medication.

The GDC explains: ‘Cardiovascular risk rises with age, therefore, while there is a younger group who are not currently at high risk of cardiovascular disease, they still have an increased lifetime risk, and they will all move into the high-risk group as they age.’

A key change that will affect virtually all patients with type 2 diabetes is that NICE now endorses modified-release metformin (MRM) first line. In previous versions of the guideline, this option was reserved for patients who were unable to tolerate standard metformin because of gastrointestinal side effects.

The GDC said that compared with standard metformin, MRM is likely to be better adhered to, countering the downstream costs of non-adherence, for example, cardiovascular and renal events, further appointments and investigations.

THE RECOMMENDATIONS

INITIAL AND SUBSEQUENT THERAPY

Recommendation: For people with type 2 diabetes and no relevant comorbidities, offer:

• Modified-release metformin (MRM), and
• An SGLT2 inhibitor

If MRM is contraindicated or not tolerated, offer an SGLT2 inhibitor as monotherapy.

For those who require further medicines to reach their glycaemic targets:

• Add a DPP-4 inhibitor to current treatment. If not tolerated or not effective, offer:
• A sulfonylurea
• Pioglitazone
• Insulin-based treatment

HEART FAILURE

Recommendation: For people with type 2 diabetes and heart failure (HF), offer:

• MRM, and
• An SGLT2 inhibitor

If MRM is contraindicated or not tolerated, offer an SGLT2 inhibitor as monotherapy.

In a significant change from the draft guidance, NICE has withdrawn its recommendation to offer a GLP-1 RA (subcutaneous semaglutide) to adults with type 2 diabetes and HF who need further medication to reach their individualised glycaemic targets. Instead NICE now recommends that clinicians offer a DDP-4 inhibitor to current treatment.

If this is contraindicated, not tolerated or not effective, add:

• A sulfonylurea, or
• An insulin-based treatment.

ASCVD

For people with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD), NICE recommends initial triple therapy with MRM, and SGLT2 inhibitor and a GLP-RA.

Recommendation: For people with type 2 diabetes and ASCVD, offer:

• MRM
• An SGLT2 inhibitor

If an adult with type 2 diabetes develops ASCVD after starting initial treatment, offer to add subcutaneous semaglutide, up to 1mg once a week to current treatment.

The GDC considers that even though recommending this class of drug for some people as part of initial therapy will increase costs, early intervention could lead to weight loss, leading to better long term prognosis, and reduced need for other long term or later stage treatment.

For adults with type 2 diabetes and ASCVD who need additional therapies to achieve glycaemic targets, offer to add:

• A sulfonylurea, or
• Pioglitazone, or
• An insulin-based treatment.

NB. Sulfonylureas and insulin-based therapies may increase hypoglycaemic events and weight gain. Pioglitazone might worsen cardiovascular outcomes, and should be avoided for people with heart failure. Clinicians should consider the benefits and risks of each treatment on a case-by-case basis.

OBESITY

Recommendation: For people with type 2 diabetes living with obesity, offer:

• MRM
• An SGLT2 inhibitor

If metformin is contraindicated or not tolerated, offer an SGLT2 inhibitor as monotherapy.

Consider adding a GLP-1 RA or tirzepatide if they have been taking initial therapy for at least 3 months and require further medication to reach their glycaemic targets. If a GLP-1 RA is contraindicated, not tolerated, not appropriate, or not effective, add

• A sulfonylurea
• Pioglitazone, or
• An insulin-based treatment.

If weight reduction is the primary aim of management, follow the recommendations in NICE's guideline on overweight and obesity management (NG246), at https://www.nice.org.uk/guidance/ng246

CHRONIC KIDNEY DISEASE

Recommendations for treatment vary according to the eGFR of the patient with both type 2 diabetes and chronic kidney disease (CKD). Prescribers are urged to refer to the individual summary of product characteristics for contraindications and precautions.

Recommendations: For people with type 2 diabetes and CKD, offer:

• eGFR above 30 ml/min/1.73m²: MRM and a SGLT2 inhibitor (either dapagliflozin or empagliflozin)
• eGFR between 20 and 30 ml/min/1.74m²: either dapagliflozin or empagliflozin and a DPP-4 inhibitor
• eGFR below 20 ml/min/1.74m²: consider a DPP-4 inhibitor.

For adults who need further medication to reach target, consider adding:

• a DPP-4 inhibitor. If already taking a DPP-4 inhibitor, or if the DPP-4 inhibitor is contraindicated, not tolerated or not effective, consider adding:
  • Pioglitazone, or
  • A sulfonylurea (if their eGFR is >30 ml/min/1.73m² or
  • An insulin-based treatment.

EARLY ONSET DIABETES

Early onset type 2 diabetes is diabetes diagnosed before the age of 40. The GDC said this group of patients has a very high lifetime risk of cardiovascular and renal complications and mortality, and is more likely to be living with obesity. Early intensive treatment can help to prevent these future negative outcomes. Therefore, a combination ofGLP-1 RA or tirzepatide with metformin and an SLGT2 inhibitor is recommended because of their combined impact on cardiovascular events, the development of end-stage renal disease, and weight loss.

Recommendation: offer modified-release metformin and an SGLT2 inhibitor, and consider adding either:

• A GLP-1 RA for its cardiovascular, renal and glycaemic benefits, or
• Tirzepatide for its glycaemic benefits.

If metformin is contraindicated or not tolerated, offer an SGLT2 inhibitor and consider adding a GLP-1 RA or tirzepatide.

FRAILTY

NICE recommends reviewing the overall treatment plan of adults with type 2 diabetes and frailty to ensure they are taking the smallest effective number of medications at the lowest effective dosage. The GDC said that concerns about adverse effects and polypharmacy meant that SGLT2 inhibitors may not be appropriate for some patients with clinically significant frailty. The GDC said there was no specific evidence to enable them to recommend a particular cut-off point, so the decision should be based on clinical judgement.

Recommendation: If the person has a level of frailty that puts them at risk of adverse events from SGLT2 inhibitors, offer:

• MRM alone
• An SGLT2 inhibitor if the person's level of frailty does not place them at risk of volume depletion or hypotension.

If metformin is contraindicated or not tolerated, and they are not at risk of adverse events from an SGLT2 inhibitor, consider SGLT2 inhibitor monotherapy; alternatively, consider monotherapy with a DPP-4 inhibitor.

If the individual with frailty requires additional medication to reach their individualised glycaemic target, consider adding a DPP-4 inhibitor. If contraindicated, not tolerated or not effective, consider adding one of the following to their current treatment:

• Pioglitazone, or
• A sulfonylurea, or
• An insulin-based treatment.

NB. Be aware that sulfonylureas and insulin-based treatments can increase the risk of hypoglycaemia and falls. Pioglitazone increases the risk of fractures and weight gain. Clinicians should consider the benefits and risks of each treatment on a case-by-case basis.

NICE does not recommend the GLP-1 RAs or tirzepatide for people with frailty, but states that as there is no inherent safety risk with these treatments for this group of people, they can still be offered if the individual has a relevant indication and frailty.

INTRODUCING MEDICINES

NICE recommends introducing initial therapies one at a time, starting with metformin and checking tolerability. Once this has been established, start an SGLT2 inhibitor as soon as metformin is at the maximum tolerated dose. If using a GLP-1 RA, start it as soon as the tolerability of the SGLT2 inhibitor has been confirmed.

Before initiating an SGLT2 inhibitor, consider whether the individual might be at risk of diabetic ketoacidosis (DKA), e.g. if they

• Have had a previous episode of DKA
• Are unwell with intercurrent illness
• Are at risk of dehydration or volume depletion
• Are following a very low carbohydrate or ketogenic diet.

When reviewing treatment, optimise the patient’s current treatment regimen before changing treatments, considering factors such as:

• Adverse effects
• Adherence to, and management of existing medicines
• The need to revisit advice about diet and self-management
• Prescribed doses and formulations

Reviewing medication

• For patients who are already taking standard-release metformin, continue if it is effective and tolerated. If it is not tolerated, offer modified-release metformin.
• If the person has reached their glycaemic and weight targets, continue medicines that have contributed to these effects.
• Consider continuing SGLT2 inhibitors for their cardiovascular or renal benefits even if they do not help the individual achieve their glycaemic or weight targets
• Stop GLP-1 RAs if:
  • The person becomes underweight (BMI under 18.5 kg/m²).
  • They do not help the person reach their individualised glycaemic target and they are not being taken for their cardiovascular benefits
• Take into account the possible adverse events from combining medications, e.g., hypoglycaemia,
• Do not offer a GLP-1RA and DPP-4 inhibitor together

INSULIN-BASED TREATMENTS

The insulin-based treatment recommendations have undergone a ‘pragmatic refresh’ to reflect the withdrawal of some insulin products and known insulin brand shortages. Based on the GDC’s clinical experience and consensus, this refresh acknowledges the increased use of analogue insulin. The committee agreed that:

• Different insulin therapies may be more useful for different people, depending on their symptoms (for example: if there is a risk of nocturnal hypoglycaemia, a longer acting basal insulin might be more suitable), and
• The added flexibility of recommending broad drug classes rather than specific insulins will support people with diabetes and healthcare professionals to choose the most suitable treatment.

1. NICE. Draft guideline on Type 2 diabetes: management; 20 August 2025. https://www.nice.org.uk/guidance/gid-ng10336/documents/450
2. NHS England. Fit for the future: 10 year health plan for England. https://www.england.nhs.uk/long-term-plan/
3. Davies MJ, ARoda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45(11):2753-86