Should an adult with type 2 diabetes and a hemoglobin A1c of about 10% who is not at target on oral therapy be started on insulin glargine (Lantus) plus metformin, and how should the initial doses be selected and titrated?

Initiating Insulin Glargine (Lantus) Plus Metformin for Type 2 Diabetes with HbA1c 10%

For an adult with type 2 diabetes and HbA1c of approximately 10% who is not at target on oral therapy, you should immediately start basal insulin glargine (Lantus) at 10 units once daily (or 0.1–0.2 units/kg body weight) at bedtime while continuing metformin at maximum tolerated dose (up to 2000 mg daily). 1, 2 This combination provides superior glycemic control compared to either agent alone, with metformin reducing total insulin requirements by 20–30% and preventing the weight gain typically associated with insulin therapy. 3, 4

Why Immediate Insulin Initiation Is Required

• HbA1c ≥10% is an absolute indication for insulin therapy because oral agents typically lower HbA1c by only 0.9–1.1%, which is insufficient to reach target control from this baseline. 3, 5
• Delaying insulin initiation at this HbA1c level prolongs exposure to severe hyperglycemia and increases the risk of both micro- and macrovascular complications. 3, 5
• Early intensive insulin therapy reverses glucotoxicity, preserves residual β-cell function, and can lead to sustained remission in newly diagnosed diabetes. 5

Initial Dosing Protocol

Starting Dose Selection

• Begin with 10 units of insulin glargine once daily at bedtime, which is the standard starting dose for insulin-naive patients with type 2 diabetes. 1, 2, 6
• Alternative weight-based approach: Start at 0.1–0.2 units/kg body weight once daily; for severe hyperglycemia (HbA1c ≥10%), use the higher end of this range (0.2 units/kg). 1, 2
• For a 70 kg patient, this translates to approximately 14 units once daily at bedtime. 2

Titration Algorithm

• Increase the dose by 2 units every 3 days if fasting glucose is 140–179 mg/dL. 1, 3, 2
• Increase the dose by 4 units every 3 days if fasting glucose is ≥180 mg/dL. 1, 3, 2
• Target fasting glucose: 80–130 mg/dL. 1, 3, 2
• If unexplained hypoglycemia (glucose <70 mg/dL) occurs, immediately reduce the dose by 10–20%. 1, 3, 2

Critical Threshold for Basal Insulin

• When basal insulin approaches 0.5–1.0 units/kg/day without achieving glycemic targets, add prandial insulin or a GLP-1 receptor agonist rather than continuing to escalate basal insulin alone. 3, 2 This prevents "over-basalization," which increases hypoglycemia risk without improving control. 3, 2

Metformin Optimization and Continuation

Why Metformin Must Be Continued

• Never discontinue metformin when adding insulin unless contraindicated—it remains foundational therapy throughout treatment intensification. 1, 3, 5, 4
• Metformin reduces total insulin requirements by 20–30% and achieves superior glycemic control compared to insulin alone. 3, 5, 4
• The combination of metformin plus insulin glargine resulted in HbA1c levels that were 10% lower (6.5% vs. 7.6%) than insulin therapy alone in randomized trials. 4
• Metformin provides proven cardiovascular mortality benefit independent of its glucose-lowering effect. 1, 5
• Metformin mitigates the weight gain commonly associated with insulin therapy—patients on insulin alone gained 3.2 kg vs. 0.5 kg with metformin plus insulin. 4

Metformin Dosing

• Optimize metformin to 2000 mg daily (1000 mg twice daily with meals) to achieve maximal glucose-lowering effect. 3, 5
• If the patient is taking less than 2000 mg daily, increase by 500 mg each week until reaching the target dose. 5
• Doses above 2000 mg (up to 2550 mg) add minimal additional benefit and increase gastrointestinal intolerance. 3, 5

Safety Considerations for Metformin

• Metformin is safe when eGFR ≥30 mL/min/1.73 m²; it is contraindicated when eGFR falls below this threshold. 1, 5, 6
• Check renal function (eGFR) at baseline and at least annually. 5
• Monitor vitamin B12 levels periodically in patients on long-term metformin, especially if anemia or peripheral neuropathy develops. 1, 5

Administration and Monitoring

Insulin Administration

• Administer insulin glargine subcutaneously once daily at the same time every day—typically at bedtime. 2, 6
• Inject into the abdominal area, thigh, or deltoid, rotating injection sites within the same region to reduce the risk of lipodystrophy. 6
• Do not administer intravenously, do not dilute, and do not mix with any other insulin or solution. 6

Glucose Monitoring

• Check fasting glucose daily during titration to guide dose adjustments. 1, 3, 2
• Patients should perform self-monitoring of blood glucose to enable self-titration of insulin dose. 7, 8
• Reassess HbA1c at 3 months after initiating therapy to determine if additional intensification is needed. 3, 5

Expected Clinical Outcomes

Glycemic Control

• With appropriate basal insulin plus metformin therapy, expect an HbA1c reduction of 2–3% from baseline (from ~10% to 7–8%) within 3 months. 3, 5
• In the Canadian INSIGHT study, adding insulin glargine was 1.68 times more likely to achieve two consecutive HbA1c levels ≤6.5% compared to conventional therapy with oral agents alone. 7
• Fasting glucose should normalize to 80–130 mg/dL within 2–4 weeks of basal insulin titration. 3, 2

Weight and Hypoglycemia

• Expect modest weight gain of 1.9 kg with insulin glargine compared to oral agents alone, but this is mitigated by continuing metformin. 7, 4
• Hypoglycemia rates are not increased when basal insulin is properly titrated compared to oral agents alone. 7

When to Intensify Further

Adding a Third Agent

• If HbA1c remains >7% after 3 months of optimized metformin plus basal insulin, add a GLP-1 receptor agonist (e.g., semaglutide, liraglutide, dulaglutide) rather than further increasing insulin dose. 3, 5
• GLP-1 receptor agonists provide an additional 0.6–0.8% HbA1c reduction, promote weight loss of 2–5 kg, carry minimal hypoglycemia risk, and offer proven cardiovascular benefit. 3, 5

Adding Prandial Insulin

• If post-prandial glucose remains >180 mg/dL despite optimized basal insulin, add prandial rapid-acting insulin starting with 4 units before the largest meal (or 10% of the basal dose). 3, 2
• Titrate prandial insulin by 1–2 units every 3 days based on 2-hour post-prandial glucose readings. 3, 2

Critical Pitfalls to Avoid

• Do not delay insulin initiation while trialing additional oral agents alone—at HbA1c 10%, combination therapy with basal insulin is required to achieve control. 3, 5
• Do not discontinue metformin when insulin is added unless contraindicated; it remains foundational therapy throughout intensification. 1, 3, 5, 4
• Avoid therapeutic inertia: intensify therapy within 3 months if HbA1c remains above target, as delays increase complication risk. 3, 5
• Do not add sulfonylureas to the metformin plus insulin regimen; they markedly raise hypoglycemia risk and lack the cardiovascular benefits of GLP-1 receptor agonists or SGLT2 inhibitors. 5
• Do not continue escalating basal insulin beyond 0.5–1.0 units/kg/day without addressing post-prandial hyperglycemia or adding adjunctive therapy, as this leads to over-basalization with increased hypoglycemia risk. 3, 2