What is the optimal management plan for a patient with type 1 or type 2 diabetes to achieve target blood glucose levels and prevent complications?

How to Treat Diabetes

Target an A1C of <7% (53 mmol/mol) for most nonpregnant adults with diabetes, achieved through lifestyle modification, metformin as first-line therapy, and rapid intensification with additional agents or insulin when targets are not met within 3 months. 1

Glycemic Targets

The primary goal is an A1C <7% (53 mmol/mol), which reduces microvascular complications (retinopathy, neuropathy, diabetic kidney disease) by 50-76% when instituted early in the disease course. 1

• For patients using continuous glucose monitoring, aim for time in range >70% (glucose 70-180 mg/dL) with time below range <4%. 1
• More stringent targets (A1C <6.5%) are appropriate for newly diagnosed patients, those on lifestyle or metformin only, patients with long life expectancy, and those without significant cardiovascular disease—if achievable without hypoglycemia. 1
• Less stringent targets (A1C <8%) are appropriate for patients with limited life expectancy, history of severe hypoglycemia, advanced complications, or extensive comorbidities. 1

Initial Therapy Approach

Start all patients with type 2 diabetes on lifestyle intervention (diet, exercise, weight loss) plus metformin immediately at diagnosis. 1

• Metformin is first-line therapy due to proven cardiovascular benefits, low hypoglycemia risk, weight neutrality, and cost-effectiveness. 1, 2
• If A1C ≥10% or fasting glucose ≥250 mg/dL with symptoms (polyuria, polydipsia, weight loss), initiate insulin therapy immediately in combination with lifestyle intervention and metformin. 1, 3
• Severely uncontrolled diabetes with catabolism requires insulin as the treatment of choice to rapidly normalize glucose levels and relieve symptoms. 1

Medication Intensification Algorithm

If A1C remains ≥7% after 3 months on metformin, add a second agent immediately—do not delay treatment intensification. 1, 3

Choice of Second Agent (Prioritize Based on Comorbidities):

For patients with established cardiovascular disease or high cardiovascular risk:

• Add a GLP-1 receptor agonist (liraglutide, semaglutide, dulaglutide) or SGLT2 inhibitor (empagliflozin, canagliflozin, dapagliflozin) with proven cardiovascular benefit. 3, 2
• SGLT2 inhibitors reduce cardiovascular death by 38%, all-cause mortality by 32%, and hospitalization for heart failure by 36%. 2
• These benefits occur independently of glucose lowering and persist even when A1C is well-controlled. 2

For patients with chronic kidney disease:

• Add an SGLT2 inhibitor, which prevents CKD progression and reduces renal adverse events independent of glucose control. 2

For patients requiring weight loss:

• Prioritize GLP-1 receptor agonists or SGLT2 inhibitors, which promote weight loss. 3
• Avoid sulfonylureas and thiazolidinediones, which cause weight gain. 3

For patients with hypoglycemia risk:

• Avoid sulfonylureas entirely, as they stimulate insulin secretion regardless of blood glucose levels and are the most common cause of hypoglycemia among oral agents. 3
• Prefer DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, or pioglitazone, which do not cause hypoglycemia when used without insulin or sulfonylureas. 4

Insulin Therapy

Insulin is essential when oral agents fail to achieve targets, and should be initiated without delay. 1, 5

When to Start Insulin:

• A1C ≥10% or fasting glucose ≥250 mg/dL with symptoms 1, 3
• A1C ≥7.5% despite optimal oral therapy 5
• Acute illness, surgery, or pregnancy 5

How to Initiate Insulin:

• Begin with basal insulin (long-acting insulin glargine or degludec) once daily, typically 10 units or 0.1-0.2 units/kg, continuing metformin. 5, 6
• Titrate basal insulin by 2-4 units every 3 days based on fasting glucose until fasting glucose is 80-130 mg/dL. 5
• If postprandial glucose remains elevated despite adequate fasting control, add rapid-acting insulin (aspart, lispro) before meals. 7, 5, 6
• Rapid-acting insulin should be injected 5-10 minutes before meals into the abdomen, thigh, buttocks, or upper arm, rotating sites to prevent lipodystrophy. 7

Insulin Regimens:

• Basal-bolus regimen (long-acting basal insulin once daily plus rapid-acting insulin before each meal) most closely mimics physiologic insulin secretion and provides optimal control. 5, 8
• Premixed insulin twice daily is an alternative for patients requiring simpler regimens, though it offers less flexibility. 5
• Metformin should be continued when starting insulin, as it reduces weight gain, lowers insulin dose requirements, and decreases hypoglycemia risk. 5

Monitoring and Reassessment

Reassess A1C every 3 months until target is achieved, then every 6 months if stable. 1, 4

• Self-monitoring of blood glucose is essential for all patients on insulin or sulfonylureas to prevent and manage hypoglycemia. 9, 5
• Fasting glucose should be used to titrate basal insulin; both fasting and postprandial glucose should be used to titrate mealtime insulin. 5
• Continuous glucose monitoring is preferred for patients with type 1 diabetes or those with frequent hypoglycemia, targeting time in range >70%. 1

Special Populations

In older adults with multiple comorbidities, prioritize preventing hypoglycemia over tight glycemic control—avoid sulfonylureas and target A1C <8%. 1, 3

In patients with renal impairment (eGFR <60 mL/min/1.73m²), adjust doses of metformin, SGLT2 inhibitors, and GLP-1 receptor agonists according to specific eGFR thresholds; metformin is contraindicated if eGFR <30. 3, 4

In patients with heart failure, avoid thiazolidinediones (pioglitazone) entirely, as they cause fluid retention and can precipitate congestive heart failure. 4

Common Pitfalls to Avoid

Never delay treatment intensification when A1C targets are not met—clinical inertia is a major barrier to achieving glycemic control. 1, 3

Never discontinue metformin or SGLT2 inhibitors solely because A1C is at target, as their cardiovascular and renal benefits are independent of glucose lowering. 2

Never allow patients to self-reduce medication doses due to side effects without addressing the underlying issue—switch to alternative agents rather than accepting poor control. 3

Never inject insulin into areas of lipodystrophy, as this causes erratic absorption and hyperglycemia; rotate injection sites consistently. 7

Never abruptly discontinue oral medications when starting insulin, as this causes rebound hyperglycemia. 5