Type 2 Diabetes Management
Start all adults with type 2 diabetes on metformin plus lifestyle modifications, and immediately add either an SGLT-2 inhibitor or GLP-1 receptor agonist as second-line therapy when glycemic control is inadequate—prioritizing SGLT-2 inhibitors for patients with heart failure or chronic kidney disease, and GLP-1 agonists for those at high stroke risk or requiring weight loss. 1
Initial Treatment Strategy
Begin metformin at 500 mg daily and titrate by 500 mg every 1-2 weeks up to 2000 mg daily in divided doses, starting at or soon after diagnosis unless contraindicated. 2 Metformin reduces hepatic gluconeogenesis, improves glucose uptake, and does not cause weight gain or significant hypoglycemia risk. 3
Exceptions Requiring Insulin First
Skip metformin and start insulin immediately if the patient presents with: 2
- Ketosis or diabetic ketoacidosis
- Random blood glucose ≥250 mg/dL
- HbA1c >9%
- Severe hyperglycemia with catabolism
- Symptomatic diabetes with polyuria, polydipsia, and weight loss
Second-Line Therapy Selection Algorithm
When metformin plus lifestyle modifications fail to achieve glycemic targets, add either an SGLT-2 inhibitor or GLP-1 receptor agonist based on the following hierarchy: 1
Prioritize SGLT-2 Inhibitors When:
- Heart failure is present (reduces hospitalization for CHF by 18-25%) 1, 4
- Chronic kidney disease exists with eGFR ≥30 mL/min per 1.73 m² (reduces CKD progression by 24-39%) 1, 5, 4
- Patient needs protection against all-cause mortality and MACE 1
Prioritize GLP-1 Receptor Agonists When:
- Increased stroke risk exists 1
- Weight loss is an important treatment goal (achieves >5% weight loss in most patients, potentially >10%) 1, 4
- Patient needs protection against all-cause mortality and MACE 1
Both drug classes reduce all-cause mortality by 12-26% and MACE over 2-5 years compared to placebo. 4
Third-Line Therapy
If dual therapy (metformin + SGLT-2i or GLP-1 RA) is insufficient, add the other cardioprotective agent to create triple therapy: metformin + SGLT-2 inhibitor + GLP-1 receptor agonist. 6 Real-world evidence demonstrates this triple combination provides superior reduction in 3-point MACE, total mortality, and heart failure compared to other combinations. 6
Medications to Avoid
Do not add DPP-4 inhibitors to metformin for reducing morbidity and mortality—this is a strong recommendation against their use based on high-certainty evidence. 1 Sulfonylureas and long-acting insulins are inferior to SGLT-2 inhibitors and GLP-1 agonists for reducing mortality and morbidity, though they retain limited value for glycemic control alone. 1, 6
Glycemic Targets and Monitoring
Target HbA1c between 7-8% for most adults with type 2 diabetes. 1 Deintensify treatment if HbA1c falls below 6.5%. 1 Monitor HbA1c every 3 months until target is reached, then at least twice yearly. 2
Self-monitoring of blood glucose may be unnecessary in patients on metformin combined with either an SGLT-2 inhibitor or GLP-1 agonist. 1
Critical Safety Consideration
When adding an SGLT-2 inhibitor or GLP-1 agonist achieves adequate glycemic control, reduce or discontinue sulfonylureas or long-acting insulins due to increased severe hypoglycemia risk. 1
Insulin Therapy
Initiate insulin when triple therapy fails to achieve glycemic targets, starting with basal insulin at 0.5 units/kg/day and titrating every 2-3 days based on glucose monitoring. 2 Approximately one-third of patients with type 2 diabetes require insulin during their lifetime. 4 Add prandial insulin if escalating basal insulin doses fail to meet targets. 2
Lifestyle Modifications
Prescribe at least 150 minutes per week of moderate-intensity aerobic activity spread over at least 3 days, with no more than 2 consecutive days without exercise. 5 Add resistance training at least twice weekly. 5 Physical activity reduces HbA1c by 0.4-1.0% and improves cardiovascular risk factors. 4
Recommend a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts, while limiting sodium to <2g per day. 5 Weight loss of at least 5% benefits overweight or obese adults with type 2 diabetes. 1, 5
Cardiovascular and Renal Protection
Initiate ACE inhibitor or ARB therapy if hypertension and albuminuria are present in patients with diabetes and chronic kidney disease. 5 Comprehensive cardiovascular risk reduction must be a major focus alongside glycemic control. 5
Common Pitfalls to Avoid
- Clinical inertia: Do not delay treatment intensification when glycemic targets are not met. 2
- Monotherapy persistence: Most patients require combination therapy as diabetes progresses—anticipate this rather than waiting for failure. 3
- Ignoring comorbidities: Always select second-line agents based on cardiovascular and renal comorbidities, not just glucose-lowering efficacy. 1