Early onset diabetes

For people diagnosed with early onset diabetes (before the age of 40), the need for triple therapy with the addition of a GLP-1 receptor agonist (liraglutide, dulaglutide or semaglutide) or tirzepatide should be considered when initiating therapy due to the increased risk of morbidity and mortality. 

Dipeptidyl peptidase 4 (DPP-4) inhibitors, sulfonylureas, pioglitazone and insulin are options (depending on the circumstances) if treatment escalation is necessary.

In the main, there are no significant changes to the recommendations for adding insulin and pioglitazone where people are not responding to other treatments and/or cannot tolerate other medicines.

Overall, monotherapy is not recommended, unless it is unavoidable. For example, to avoid risks from polypharmacy in people with multiple health conditions or in frailty or where there are contraindications to other medicines.

Comorbidities

For people with diabetes and chronic kidney disease, and an estimated glomerular filtration rate (eGFR) less than 30ml/min/1.73m², the recommendations are tailored to the degree of kidney function. Metformin is not recommended for these people.

A DPP-4 inhibitor should be offered to people with an eGFR below 20ml/min/1.73m². Those with an eGFR between 20ml/min/1.73m² and 30ml/min/1.73m² should be offered dapagliflozin or empagliflozin plus a DPP-4 inhibitor.

Of note is the approach to managing diabetes in those living with obesity without other significant comorbidities. Unlike some major guidelines (e.g. the American Diabetes Association), NICE has not recommended immediate use of GLP-1 receptor agonists.

The recommendation for people living with obesity without other significant comorbidities is the same as for the wider population without significant comorbidity. 

Adding GLP-1 receptor agonists to the treatment of people living with diabetes and obesity can be considered if further treatment is needed to reach personal HbA1c target, after at least three months of initial treatment with metformin and an SGLT-2 inhibitor.

These recommendations indicate that initiating the right drug at the right time is essential to improving health outcomes and reducing the risk of complications.

They also recognise that those who are frail might do better with fewer medicines. Indeed, one of the major points is the shift from a purely glucose-lowering approach to one that focuses equally on cardiovascular and renal protection.