Alternative Medications for Type 2 Diabetes

Primary Alternative: GLP-1 Receptor Agonists

The American Diabetes Association/Kidney Disease: Improving Global Outcomes (ADA/KDIGO) consensus recommends a GLP-1 receptor agonist with proven cardiovascular benefit for patients with type 2 diabetes and chronic kidney disease (CKD) who do not meet their individualized glycemic target with metformin and/or an SGLT2 inhibitor or who are unable to use these drugs 1
GLP-1 receptor agonists are the guideline-recommended alternative when SGLT2 inhibitors cannot be used, particularly for patients with established atherosclerotic cardiovascular disease or high cardiovascular risk 4, 3
Liraglutide (Victoza) has demonstrated cardiovascular mortality reduction, with particularly strong benefits in patients with eGFR <60 mL/min/1.73 m² 2
Semaglutide (Ozempic) has proven cardiovascular benefits with once-weekly dosing 4
Dulaglutide has demonstrated cardiovascular benefits and showed slower GFR decline compared to insulin glargine in patients with moderate-to-severe CKD 2

GLP-1 receptor agonists can achieve an HbA1c reduction of 0.7-1.0% 3, 5
Significant weight loss can be expected with GLP-1 receptor agonists, unlike sulfonylureas or insulin 3, 5
GLP-1 receptor agonists have a low hypoglycemia risk when used without insulin or sulfonylureas 5
Cardiovascular mortality reduction can be expected in high-risk patients treated with GLP-1 receptor agonists 4, 2
Renal protective effects, including reduced albuminuria and slower eGFR decline, can be expected with GLP-1 receptor agonists 2

Dapagliflozin is approved for use down to eGFR 25 mL/min/1.73 m² 2
Canagliflozin has demonstrated renal benefits in the CREDENCE trial with 30% reduction in development of ESRD 6

DPP-4 inhibitors are reasonable alternatives with intermediate glucose-lowering effect (0.7-1.0% HbA1c reduction) and low hypoglycemia risk 3, 5
Sulfonylureas (glimepiride or glipizide) provide high glucose-lowering effect (0.9-1.1% HbA1c reduction) but have moderate to high hypoglycemia risk and weight gain 5, 4

Metformin should always be continued when adding a second agent unless contraindicated (eGFR <30 mL/min/1.73 m²) or not tolerated 1, 6, 3
Evaluate HbA1c after approximately 3 months of the new therapy and proceed to triple therapy or insulin if the A1C target is not achieved 3
Initiate insulin therapy immediately if the patient has A1C ≥10% (86 mmol/mol) and/or blood glucose ≥300 mg/dL with symptoms, or ketosis/ketoacidosis 3