What is the treatment for type 2 diabetes?

Treatment of Type 2 Diabetes

Initiate metformin immediately at diagnosis alongside lifestyle modifications, then add an SGLT-2 inhibitor if the patient has heart failure or kidney disease, or add a GLP-1 receptor agonist if cardiovascular risk is high or weight loss is needed. 1, 2

Immediate First-Line Treatment

Start metformin 500 mg daily with food, increasing by 500 mg every 1-2 weeks to reach the optimal dose of 2000 mg daily in divided doses. 1, 3 This recommendation is based on metformin's proven efficacy in reducing microvascular complications, excellent safety profile, minimal hypoglycemia risk, and cost-effectiveness. 4, 2

The only exceptions requiring insulin from the start are: 4, 2

• Random glucose ≥250 mg/dL (13.9 mmol/L) or A1C ≥8.5% (69 mmol/mol)
• Presence of diabetic ketoacidosis or marked ketosis
• Severe symptoms (polyuria, polydipsia, weight loss)

Lifestyle Modifications (Concurrent, Not Sequential)

Lifestyle changes must be implemented immediately and reinforced continuously throughout treatment—not as a preliminary step before medication. 4, 1

Prescribe at least 150 minutes weekly of moderate-intensity aerobic activity (50-70% maximum heart rate) spread over at least 3 days, combined with resistance training. 4, 1 Physical activity alone can reduce A1C by 0.4-1.0%. 2

Target 5-10% body weight reduction in overweight/obese patients through high-intensity interventions (≥16 sessions over 6 months) with a 500-750 kcal/day energy deficit. 1, 5 This produces clinically significant improvements in glycemic control. 1

Second-Line Treatment Selection (When Metformin Fails After 3-6 Months)

The choice of add-on therapy is dictated by comorbidities, not arbitrary preference: 1, 2

Add an SGLT-2 inhibitor if the patient has: 1, 2

• Heart failure (reduces hospitalizations by 18-25%)
• Chronic kidney disease (reduces progression by 24-39%)
• Need to reduce all-cause mortality and major cardiovascular events

Add a GLP-1 receptor agonist if the patient has: 1, 2

• High cardiovascular risk (reduces events by 12-26%)
• Need for significant weight loss (>5% in most patients, often >10%)
• History of stroke (specific reduction benefit)

Both drug classes reduce all-cause mortality by 2.7-4.9% and have been proven superior to placebo in large randomized trials over 2-5 years. 2 Most trial participants were already taking metformin, supporting this sequential approach. 2

Critical Safety Adjustment

When adding an SGLT-2 inhibitor or GLP-1 receptor agonist achieves adequate glycemic control, reduce or discontinue any existing sulfonylureas or long-acting insulin due to severe hypoglycemia risk. 1 This is a commonly missed but essential step.

Glycemic Targets and Monitoring

Target A1C between 7-8% for most adults. 1 More stringent targets (<6.5%) are appropriate only for newly diagnosed patients with long life expectancy and no cardiovascular disease. 4 Less stringent targets (<8%) apply to those with severe hypoglycemia history, limited life expectancy, or advanced complications. 4

De-intensify pharmacotherapy if A1C falls below 6.5%. 1

Assess glycemic status at least every 3 months. 1 Home glucose monitoring may be unnecessary in patients on metformin alone or combined with SGLT-2 inhibitors or GLP-1 receptor agonists (low hypoglycemia risk). 1

Alternative Second-Line Options (When SGLT-2i/GLP-1RA Unavailable)

If cost or availability prevents use of SGLT-2 inhibitors or GLP-1 receptor agonists: 4, 1

• Sulfonylureas (higher hypoglycemia risk, weight gain)
• DPP-4 inhibitors (though the American College of Physicians recommends against adding DPP-4 inhibitors to metformin) 1
• Thiazolidinediones like pioglitazone (fracture risk, heart failure concerns) 6

Prescribe generic medications when available rather than brand-name alternatives. 1 Discuss medication costs explicitly with patients when selecting add-on therapy. 1

Insulin Therapy

Approximately one-third of patients require insulin during their lifetime. 2 Initiate insulin when: 4

• Glycemic targets are not met despite maximum oral therapy
• A1C ≥8.5% at presentation
• Metformin is contraindicated (renal/hepatic insufficiency)

Start with long-acting basal insulin at 0.5 units/kg/day, titrating every 2-3 days based on glucose monitoring. 4 Add prandial insulin if basal insulin alone fails to achieve targets. 4

Multidisciplinary Team Approach

Treatment requires coordination between physicians, diabetes educators, registered dietitians, and mental health professionals. 4, 1 Plans must integrate dietary improvement, weight management, sleep health, physical activity, stress management, and comorbidity treatment. 1

Common Pitfalls to Avoid

• Do not delay metformin initiation while attempting lifestyle changes alone—start both simultaneously. 4
• Do not add DPP-4 inhibitors to metformin as second-line therapy when better options exist. 1
• Do not continue sulfonylureas or insulin at full doses after adding SGLT-2 inhibitors or GLP-1 receptor agonists. 1
• Do not ignore cardiovascular and renal comorbidities when selecting second-line agents—these should drive the choice. 1, 2