What are the latest pharmacological recommendations for managing type 2 diabetes?

Latest Pharmacological Recommendations for Managing Type 2 Diabetes

Metformin remains the preferred first-line pharmacological agent for most patients with type 2 diabetes, with SGLT-2 inhibitors or GLP-1 receptor agonists strongly recommended as add-on therapy when glycemic control is inadequate, particularly for patients with cardiovascular disease, heart failure, or chronic kidney disease. 1, 2

First-Line Therapy

• Metformin should be initiated at diagnosis of type 2 diabetes unless contraindicated or not tolerated 1, 2
• Metformin is effective, safe, inexpensive, and may reduce risk of cardiovascular events and death 1, 3
• Extended-release metformin improves gastrointestinal tolerability and allows once-daily dosing 4
• Long-term metformin use may be associated with vitamin B12 deficiency; periodic testing is recommended, especially in patients with anemia or peripheral neuropathy 1, 2

Second-Line Therapy Options

When to Add Second-Line Therapy

• Consider adding a second agent when A1C remains above target after approximately 3 months on metformin monotherapy 1
• Consider initiating dual therapy in newly diagnosed patients with A1C ≥1.5% above their glycemic target 1
• Early insulin introduction should be considered if there is ongoing catabolism (weight loss), significant hyperglycemia symptoms, or very high A1C levels (>10%) or blood glucose levels (≥300 mg/dL) 1

Preferred Second-Line Options

SGLT-2 Inhibitors

• Strongly recommended as add-on therapy to metformin when glycemic control is inadequate 1, 2
• Provide significant benefits in reducing all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization for heart failure 1, 2
• Should be prioritized in patients with heart failure or chronic kidney disease 1, 2
• Canagliflozin has demonstrated significant reductions in HbA1c compared to placebo when used as monotherapy or in combination with other agents 5

GLP-1 Receptor Agonists

• Strongly recommended as add-on therapy to metformin when glycemic control is inadequate 1, 2
• Provide significant benefits in reducing all-cause mortality, major adverse cardiovascular events, and stroke 1, 2
• Should be prioritized in patients with increased stroke risk or when weight loss is an important treatment goal 1, 2
• Preferred over insulin when possible in patients needing greater glucose lowering than can be obtained with oral agents 1

Special Populations and Considerations

Cardiovascular Disease

• For patients with established atherosclerotic cardiovascular disease or indicators of high risk, SGLT-2 inhibitors or GLP-1 receptor agonists with demonstrated cardiovascular benefit should be included as part of the glucose-lowering regimen independent of A1C 1, 6
• Among patients with atherosclerotic cardiovascular disease at high risk of heart failure or in whom heart failure coexists, SGLT-2 inhibitors are preferred 1

Chronic Kidney Disease

• For patients with type 2 diabetes and chronic kidney disease, SGLT-2 inhibitors should be prioritized after metformin 1, 6
• Metformin can be safely used in patients with eGFR ≥30 mL/min/1.73 m² 1

Glycemic Targets and Monitoring

• Target HbA1c levels between 7% and 8% for most adults with type 2 diabetes 1, 2
• Consider deintensifying treatment in patients with HbA1c <6.5% 1, 2
• Self-monitoring of blood glucose might be unnecessary in patients on metformin combined with either SGLT-2 inhibitors or GLP-1 agonists 1, 2

Important Considerations and Caveats

• When SGLT-2 inhibitors or GLP-1 agonists provide adequate glycemic control, consider reducing or discontinuing sulfonylureas or long-acting insulins to minimize hypoglycemia risk 1, 2
• Sulfonylureas and long-acting insulins are inferior to SGLT-2 inhibitors and GLP-1 agonists for mortality and morbidity outcomes but may still have value for glycemic control 1, 2
• The benefits and harms of using multiple add-on treatments beyond the initial combination are not well established 1, 2
• Recent evidence suggests that in individuals with type 2 diabetes who would benefit from cardio-renal protection, SGLT-2 inhibitors and GLP-1 receptor agonists may be considered as first-line therapy instead of metformin 7, 6