What can be added to metformin for uncontrolled type 2 diabetes?

<keypoints> - **With CVD, CV risk factors, or CKD**: add an **SGLT2 inhibitor** first (e.g. dapagliflozin, empagliflozin); if not tolerated/contraindicated, a **GLP-1 receptor agonist** is recommended - **Without CVD/CKD**: an **SGLT2i**, **GLP-1 RA**, or **DPP-4 inhibitor** may be added to metformin - **Sulphonylureas** are conditionally recommended **against** as first-choice add-on due to hypoglycaemia risk - **PBS restrictions** apply: GLP-1 RA and SGLT2i **cannot** be co-prescribed for glycaemic control; use either a DPP-4i or GLP-1 RA, not both </keypoints>

Second-Line Options (Add-on to Metformin)

The Australian Diabetes Society (ADS) June 2024 algorithm guides agent selection based on comorbidities, side-effect profile, contraindications, and cost.

Patients with CVD, CV risk factors, or CKD

The ADS and Living Evidence Guidelines recommend:

1. SGLT2 inhibitor (dapagliflozin, empagliflozin): preferred add-on, with proven cardiovascular and renal benefits independent of glucose-lowering effect
2. GLP-1 receptor agonist (dulaglutide, semaglutide, exenatide, liraglutide): recommended where SGLT2i is not tolerated or contraindicated; reduces MACE and slows CKD progression
3. DPP-4 inhibitor (sitagliptin, linagliptin, saxagliptin, vildagliptin, alogliptin): only if both SGLT2i and GLP-1 RA are not tolerable or contraindicated

Patients without CVD/CKD (glycaemic control focus)

An SGLT2i, GLP-1 RA, or DPP-4 inhibitor can be added to metformin. Choice should consider:

• Weight: SGLT2i and GLP-1 RA promote weight loss; DPP-4i are weight neutral; SU cause weight gain
• Hypoglycaemia risk: SGLT2i, GLP-1 RA, and DPP-4i have low hypoglycaemia risk; SU carry significant risk