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

Key Points

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

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:

SGLT2 inhibitor (dapagliflozin, empagliflozin): preferred add-on, with proven cardiovascular and renal benefits independent of glucose-lowering effect
GLP-1 receptor agonist (dulaglutide, semaglutide, exenatide, liraglutide): recommended where SGLT2i is not tolerated or contraindicated; reduces MACE and slows CKD progression
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
Cost and PBS access

Other add-on agents

Sulphonylurea (gliclazide, glimepiride): conditionally recommended against as first-choice add-on due to hypoglycaemia and weight gain, but remains an option when other agents cannot be used
Insulin: consider early if blood glucose is very high or symptomatic
Thiazolidinedione (pioglitazone): less commonly used; conditionally recommended against as first choice due to heart failure risk
Acarbose: less commonly used; PBS-approved option

Key PBS Considerations

SGLT2i and GLP-1 RA cannot be co-prescribed under PBS for glycaemic control (unless the SGLT2i is for a separate indication such as heart failure or CKD)
When adding incretin therapy, use either a DPP-4i or GLP-1 RA, not both together
Review any agent that has not reduced HbA1c by ≥0.5% after 3 months, considering both glycaemic and non-glycaemic benefits

Agent class	HbA1c reduction	Weight effect	Hypo risk	CV/renal benefit	PBS add-on to metformin
SGLT2i	~0.5-0.8%	Loss	Low	Yes	Yes
GLP-1 RA	~1.0-1.5%	Loss	Low	Yes (some agents)	Yes (with restrictions)
DPP-4i	~0.5-0.8%	Neutral	Low	Neutral	Yes
Sulphonylurea	~1.0-1.5%	Gain	High	No	Yes
TZD	~0.5-1.0%	Gain

See sources cited

Evidence Validator

Heidi Clinical Team2 Contributions

Dr. Jono O'Sullivan-Scott

Emergency Medicine•AU

Validated May 12, 2026Updated May 12, 2026

Explore in Heidi Evidence Browse more answers

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:

SGLT2 inhibitor (dapagliflozin, empagliflozin): preferred add-on, with proven cardiovascular and renal benefits independent of glucose-lowering effect

GLP-1 receptor agonist (dulaglutide, semaglutide, exenatide, liraglutide): recommended where SGLT2i is not tolerated or contraindicated; reduces MACE and slows CKD progression

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

Cost and PBS access

Other add-on agents

Sulphonylurea (gliclazide, glimepiride): conditionally recommended against as first-choice add-on due to hypoglycaemia and weight gain, but remains an option when other agents cannot be used

Insulin: consider early if blood glucose is very high or symptomatic

Thiazolidinedione (pioglitazone): less commonly used; conditionally recommended against as first choice due to heart failure risk

Acarbose: less commonly used; PBS-approved option

Key PBS Considerations

SGLT2i and GLP-1 RA cannot be co-prescribed under PBS for glycaemic control (unless the SGLT2i is for a separate indication such as heart failure or CKD)

When adding incretin therapy, use either a DPP-4i or GLP-1 RA, not both together

Review any agent that has not reduced HbA1c by ≥0.5% after 3 months, considering both glycaemic and non-glycaemic benefits

Agent class	HbA1c reduction	Weight effect	Hypo risk	CV/renal benefit	PBS add-on to metformin
SGLT2i	~0.5-0.8%	Loss	Low	Yes	Yes
GLP-1 RA	~1.0-1.5%	Loss	Low	Yes (some agents)	Yes (with restrictions)
DPP-4i	~0.5-0.8%	Neutral	Low	Neutral	Yes
Sulphonylurea	~1.0-1.5%	Gain	High	No	Yes
TZD	~0.5-1.0%	Gain

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

Key Points

Second-Line Options (Add-on to Metformin)

Patients with CVD, CV risk factors, or CKD

Patients without CVD/CKD (glycaemic control focus)

Other add-on agents

Key PBS Considerations

How is every Heidi Answer reviewed?

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

Key Points

Second-Line Options (Add-on to Metformin)

Patients with CVD, CV risk factors, or CKD

Patients without CVD/CKD (glycaemic control focus)

Other add-on agents

Key PBS Considerations

How is every Heidi Answer reviewed?