Management of Type 2 Diabetes with Alternative Medications

Introduction to Alternative Therapies

The American College of Physicians recommends adding an SGLT-2 inhibitor or GLP-1 receptor agonist to metformin, prioritizing SGLT-2 inhibitors for patients with heart failure or chronic kidney disease, and GLP-1 receptor agonists for those with high stroke risk or when weight loss is a priority 1, 2

SGLT-2 inhibitors, such as empagliflozin, canagliflozin, or dapagliflozin, reduce all-cause mortality, major adverse cardiovascular events (MACE), chronic kidney disease progression, and heart failure hospitalization, with benefits consistent across the full spectrum of cardiovascular risk 1, 2
The American Diabetes Association recommends SGLT-2 inhibitors as the preferred first-line alternative when metformin is contraindicated or not tolerated, based on their proven cardiovascular and renal protection independent of metformin use 3

GLP-1 receptor agonists, such as semaglutide, liraglutide, or dulaglutide, are the guideline-recommended alternative when SGLT-2 inhibitors cannot be used, particularly for patients with established atherosclerotic cardiovascular disease or high cardiovascular risk, and reduce all-cause mortality, MACE, and stroke risk 1, 2, 4

If atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease is present, add an SGLT-2 inhibitor as the preferred agent for patients with heart failure or CKD (eGFR ≥30 mL/min/1.73 m²) 1, 2, 5
If high stroke risk or total body weight loss is an important treatment goal, add a GLP-1 receptor agonist as the preferred agent 1, 2

Continue metformin when adding a second agent unless contraindicated (eGFR <30 mL/min/1.73 m²) or not tolerated, as combination therapy is more effective than switching 4, 3, 5
Reassess HbA1c after 3 months of the new therapy and proceed to triple therapy or insulin if the A1C target is not achieved 6, 4, 5

Avoid delaying treatment intensification when glycemic targets are not met; recommendations for treatment intensification should not be delayed 6
Sulfonylureas and long-acting insulins are inferior to SGLT-2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control 1, 2