Initial assessment — Clinical priorities
In type 2 diabetes, therapeutic selection is guided by clinical priorities. The first step is to identify established atherosclerotic cardiovascular disease (ASCVD). If present, treatment with proven cardiovascular benefit should be prioritised, namely SGLT2 inhibitors or GLP-1 receptor agonists. Combination therapy may be considered when residual risk remains high, regardless of glycated haemoglobin or previous metformin use.
Primary prevention in high cardiovascular risk
In the absence of ASCVD, assess for high cardiovascular risk, defined by the aggregation of multiple risk factors. In these patients, the approach is similar to secondary prevention, with SGLT2 inhibitors or GLP-1 receptor agonists recommended as first choice, with the possibility of combination therapy when clinically appropriate.
Heart failure
If cardiovascular risk is not the dominant driver, assess for heart failure (HF). In these patients, SGLT2 inhibitors are first-line therapy due to their consistent reduction in hospitalisations and cardiovascular events, regardless of ejection fraction. GLP-1 receptor agonists may be added to optimise glycaemic control or weight loss.
Chronic kidney disease
The next step is to assess for chronic kidney disease (CKD), particularly when albuminuria is present. In these cases, SGLT2 inhibitors are recommended to slow renal progression and reduce cardiovascular events. If albuminuria persists, finerenone may be considered. Combination with a GLP-1 receptor agonist is appropriate when additional metabolic control or weight loss is required.
Weight priority
When there is no cardiorenal priority, assess the clinical indication for weight loss, such as obesity, sleep apnoea, resistant hypertension or metabolic liver disease. In these patients, select drugs with high weight-loss efficacy, namely high-dose semaglutide or tirzepatide. Reassess after 3 to 6 months and consider adding an SGLT2 inhibitor when necessary.
Metabolic pathway — glycaemia, hypoglycaemia and cost
In the absence of cardiorenal or weight-related priorities, the decision is guided by glycaemic efficacy, risk of hypoglycaemia and cost. Metformin remains useful as a weight-neutral and cost-effective drug when tolerated. DPP-4 inhibitors are an option when low hypoglycaemia risk and good tolerability are desired. SGLT2 inhibitors and GLP-1 receptor agonists remain valid options in this pathway. Sulfonylureas, basal insulin and TZDs may be used if glycaemic control is insufficient, but should be weighed against the risk of hypoglycaemia, weight gain or fluid retention.
Individualised glycaemic targets
Targets for glycated haemoglobin should be adjusted according to age, comorbidities, risk of hypoglycaemia and frailty. In adults with low comorbidity burden, targets ≤ 7% may be appropriate. In older or frail patients, targets between 7.5% and 8.5% are appropriate, prioritising safety and quality of life.
Reassessment and treatment intensification
Reassessment should occur after 3 to 6 months, integrating glycaemic control, weight, renal function, adverse effects and patient preferences.
Above target
Proceed with treatment intensification through logical add-on therapy, maintaining drugs with cardiorenal or weight-related benefit even if the HbA1c target has been achieved.
Within target
Maintain therapy, avoiding unnecessary discontinuation of drugs with structural benefit.
Below what is required
Consider selective deprescribing, especially of sulfonylureas, basal insulin or TZDs, to reduce hypoglycaemia and adverse metabolic impact.
