What is the recommended treatment for a patient with type 2 diabetes (T2D) and significant insulin resistance, including the use of metformin and insulin, such as glargine (basal insulin) or detemir, to achieve optimal glycemic control?

Combining Insulin and Metformin for Type 2 Diabetes with High Glucose

Metformin should be continued when initiating basal insulin therapy in patients with type 2 diabetes, unless contraindicated, as this combination provides superior glycemic control with reduced insulin requirements and less weight gain compared to insulin alone. 1

Foundation Therapy: Metformin Must Continue

Continue metformin at maximum tolerated dose (up to 2000-2500 mg daily) when adding insulin therapy. 1 Metformin remains the cornerstone of type 2 diabetes treatment even during insulin intensification because it:

• Reduces hepatic glucose production, complementing insulin's peripheral effects 2
• Decreases total insulin requirements by approximately 20-30% 3, 4
• Prevents or minimizes weight gain associated with insulin therapy 3, 5
• Does not increase hypoglycemia risk when combined with basal insulin 1, 3

The only exceptions are standard metformin contraindications: significant renal impairment, acute illness with risk of lactic acidosis, or documented intolerance 1.

Initiating Basal Insulin with Metformin

Starting Dose Algorithm

For insulin-naive patients with type 2 diabetes on metformin, start basal insulin (glargine or detemir) at 10 units once daily OR 0.1-0.2 units/kg body weight. 1, 6, 7

For patients with severe hyperglycemia (HbA1c ≥9%, fasting glucose ≥300-350 mg/dL, or HbA1c 10-12% with symptoms), start with higher doses of 0.3-0.5 units/kg/day as total daily insulin, using a basal-bolus regimen from the outset. 1, 6

Titration Protocol

Increase basal insulin by 2-4 units every 3 days until fasting plasma glucose reaches 80-130 mg/dL: 1, 6

• If fasting glucose 140-179 mg/dL: increase by 2 units every 3 days
• If fasting glucose ≥180 mg/dL: increase by 4 units every 3 days
• If hypoglycemia occurs: reduce dose by 10-20% immediately 6

Daily fasting blood glucose monitoring is essential during titration. 1, 6

Choosing Between Glargine and Detemir

Both insulin glargine and detemir provide equivalent glycemic control when combined with metformin, with minor differences in dosing and side effects. 8, 4

• Glargine: Typically dosed once daily in the evening, requires lower total daily dose, associated with slightly more weight gain 8, 4
• Detemir: May require twice-daily dosing in 14-57% of patients, associated with less weight gain but higher total daily dose requirements 1, 8

The LANMET study demonstrated that glargine plus metformin achieved similar HbA1c reduction (7.14%) compared to NPH plus metformin (7.16%), but with significantly less symptomatic hypoglycemia during the first 12 weeks (4.1 vs 9.0 episodes/patient-year, p<0.05) and better pre-dinner glucose control. 4

Critical Threshold: When to Add Prandial Insulin

When basal insulin exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day, add prandial insulin rather than continuing to escalate basal insulin alone. 1, 6 This threshold prevents "overbasalization"—a dangerous pattern where excessive basal insulin masks inadequate mealtime coverage.

Clinical Signs of Overbasalization 6:

• Basal insulin dose >0.5 units/kg/day
• Bedtime-to-morning glucose differential ≥50 mg/dL
• Hypoglycemia episodes
• High glucose variability
• HbA1c remains above target despite controlled fasting glucose

Start prandial insulin with 4 units of rapid-acting insulin (lispro, aspart, or glulisine) before the largest meal, OR use 10% of the current basal dose. 1, 6 Titrate by 1-2 units every 3 days based on 2-hour postprandial glucose readings. 6

Managing Other Oral Agents

Discontinue sulfonylureas when advancing beyond basal-only insulin to prevent excessive hypoglycemia. 5 A 2010 study demonstrated that continuing secretagogues with basal insulin and metformin resulted in significantly more hypoglycemia and weight gain compared to stopping them, despite lower insulin doses (0.6 vs 0.8 units/kg/day). 5

Consider discontinuing other oral agents (DPP-4 inhibitors, sulfonylureas) when initiating basal insulin, but continue metformin. 1 Thiazolidinediones may be continued for their complementary insulin-sensitizing effects, though weight gain and heart failure risk must be considered. 2

Common Pitfalls to Avoid

• Never delay insulin initiation in patients not achieving glycemic goals with oral medications alone—this prolongs hyperglycemia exposure and increases complication risk 1
• Never discontinue metformin when starting insulin unless contraindicated—this leads to higher insulin requirements and more weight gain 1, 5
• Never continue escalating basal insulin beyond 0.5-1.0 units/kg/day without adding prandial coverage—this causes overbasalization with increased hypoglycemia and suboptimal control 1, 6
• Never rely on sliding scale insulin as monotherapy—scheduled basal-bolus regimens are superior for glycemic control and reducing complications 6

Administration Guidelines

• Administer basal insulin subcutaneously once daily at the same time each day (any time, but consistent) 7
• Rotate injection sites within the same region (abdomen, thigh, or deltoid) to prevent lipodystrophy 7
• Do not dilute, mix, or administer glargine intravenously or via insulin pump 7
• Provide patient education on injection technique, glucose monitoring, hypoglycemia recognition/treatment, and sick day management 1