The National Institute for Health and Care Excellence (NICE) has published final guidance recommending that most people newly diagnosed with type 2 diabetes be offered SGLT2 inhibitors alongside metformin as initial treatment. 

The updated recommendations represent a major shift in clinical practice, as most patients previously began treatment with metformin monotherapy before additional medicines were added following treatment failure.

Statistics from Diabetes UK indicate that around 4.6 million people in the UK live with diabetes, with 9 in 10 having type 2 diabetes, while a further 1.3 million people may have undiagnosed type 2 diabetes.

The change means approximately 810,000 additional people in the UK could benefit from these cardiorenal protective medicines.

Cardiorenal Protection Beyond Glycaemic Targets

SGLT2 inhibitors work by helping the kidneys eliminate excess sugar from the body, but their benefits extend beyond glycaemic control. The drugs provide significant cardiovascular and renal protection, particularly important given that heart disease is the leading cause of death among people with type 2 diabetes.

Analysis by NICE suggests the earlier introduction of SGLT2 inhibitors, combined with expanded use of GLP-1 receptor agonists and tirzepatide for specific populations, could prevent approximately 17,000 deaths over 3 years by reducing heart attacks, strokes, and kidney complications.

Superiority of Early Dual Therapy

Network and pairwise meta-analyses demonstrated that combining metformin with an SGLT2 inhibitor is more clinically effective at reducing A1c, weight, and cardiovascular events compared to metformin alone or other dual therapy combinations. 

The evidence showed reductions in cardiovascular mortality, myocardial infarction, non-fatal stroke, and heart failure hospitalisation, with specific benefits including preventing 16 major adverse cardiovascular events per 1000 patients over 3 years.

Key Clinical Recommendations

The guidance recommends slow-release metformin formulations to reduce gastrointestinal side effects that often discourage patients from continuing treatment.

Medicines should be introduced stepwise, beginning with metformin to assess tolerability before adding SGLT2 inhibitors. Healthcare providers must assess diabetic ketoacidosis risk factors before SGLT2 inhibitor initiation and implement appropriate safety protocols.

Tailored Approaches for Specific Populations

The 2026 update emphasises a "personalised" rather than "one-size-fits-all" approach, with specific protocols for high-risk and vulnerable cohorts:

• Early-onset diabetes (diagnosed before age 40): Patients face higher lifetime cardiovascular and renal risk and may benefit from earlier escalation to a GLP-1 receptor agonist or tirzepatide.
• Renal impairment: Patients with an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m² receive standard combination therapy. For those with an eGFR between 20 and 30 mL/min/1.73 m² (severe impairment), the guidance recommends dapagliflozin or empagliflozin in combination with a dipeptidyl peptidase 4 (DPP-4) inhibitor.
• Frail patients: Treatment should pivot toward symptom control and avoiding hypoglycaemia rather than aggressive A1c targets, with DPP-4 inhibitors preferred for their minimal side-effect profile.
• Atherosclerotic cardiovascular disease: Subcutaneous semaglutide (up to 1 mg weekly) is recommended as the preferred GLP-1 receptor agonist for patients with established cardiovascular disease.
• Patients with heart failure: SGLT2 inhibitors offer benefits for protecting cardiac function in this population.
• Expanded glucose-monitoring access: The guidance significantly expands access to intermittently scanned continuous glucose monitoring for adults with type 2 diabetes using insulin, particularly those experiencing recurrent or severe hypoglycaemic events.

Addressing Treatment Disparities

Analysis of anonymised records from nearly 590,000 people revealed that SGLT2 inhibitors are not prescribed equitably across populations, being often underprescribed to women, older people, and Black patients. The revised recommendations include provisions to monitor treatment access and address these disparities.

Economic Impact and Implementation 

The NHS is projected to save significant funds because dapagliflozin, one of the most prescribed SGLT2 medicines, is now available as a clinically equivalent generic version. Estimated cumulative savings for 2025/26 and 2026/27 from generic dapagliflozin total £560 million, which could be reinvested in other diabetes care areas, such as education programmes and community support services. 

The guidance also endorses biosimilar insulin products as cost-effective alternatives that could deliver substantial savings to the NHS.

The guidance incorporates recommendations for managing periodontitis in patients with type 2 diabetes, recognising the bidirectional relationship between these conditions, and recommending routine discussion of periodontitis risk during annual diabetes reviews.