Do we inject insulin pre-meal and take metformin (biguanide) pre or post meal?

Insulin and Metformin Timing Relative to Meals

Insulin Administration Timing

Prandial insulin should be injected 0-15 minutes before meals to achieve optimal postprandial glucose control. 1, 2

Rapid-Acting Insulin Analogs (Lispro, Aspart, Glulisine)

• Administer rapid-acting insulin 0-15 minutes before meals to align insulin action with carbohydrate absorption 1, 2
• The rapid-acting analogs reach peak action within 30-90 minutes, requiring pre-meal administration to match meal-related glucose excursions 2
• Point-of-care glucose testing should be performed immediately before meals when using prandial insulin 1, 2

Special Circumstances for Post-Meal Insulin

• If oral intake is poor or uncertain, administer prandial insulin immediately after the patient eats, with the dose adjusted for the actual amount consumed 1
• This safer approach prevents hypoglycemia when meal consumption is unpredictable 1
• Research demonstrates that postprandial insulin administration can maintain glucose concentrations within treatment guidelines when doses are adjusted for actual meal size, though preprandial injection produces superior glucose profiles 3

Regular Human Insulin

• Regular insulin requires a longer injection-meal interval of approximately 30 minutes before meals due to its delayed onset of action 4, 5
• However, studies show minimal clinical advantage of a 30-minute interval versus 5 minutes in well-controlled patients on basal-bolus regimens 5

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Metformin Administration Timing

Metformin should be taken before meals, not with or after meals, to optimize glucose-lowering effects and GLP-1 stimulation. 1, 6

Optimal Timing Strategy

• Administer two-thirds of the total daily metformin dose immediately before the largest meal (typically dinner), and one-third before the morning meal 1
• Recent evidence demonstrates that metformin given 30-60 minutes before enteral glucose produces significantly greater glucose reduction compared to administration at mealtime 6
• Pre-meal metformin administration enhances GLP-1 secretion, which only occurs when metformin is given at least 30 minutes before glucose intake 6

Mechanism Supporting Pre-Meal Timing

• Metformin's glucose-lowering effect is mediated partly through gastrointestinal mechanisms, including delayed glucose absorption and enhanced GLP-1 secretion 6
• The GLP-1 response requires metformin to be present in the intestine before nutrient arrival 6
• Maximum insulin-sparing effects occur 2 hours after meals when metformin is properly timed 7

Practical Implementation

• For patients on twice-daily metformin: give the larger dose (approximately 67% of total daily dose) before the evening meal and the smaller dose (33%) before breakfast 1
• For patients on three-times-daily dosing: administer each dose 15-30 minutes before meals to maximize the glucose-lowering and GLP-1-enhancing effects 6

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Critical Safety Considerations

Insulin Pitfalls to Avoid

• Never administer rapid-acting insulin 30 minutes before meals like regular insulin, as this defeats the purpose of rapid-acting analogs and increases between-meal hypoglycemia risk 2
• Avoid intramuscular injection, which causes unpredictable absorption and frequent unexplained hypoglycemia 1
• Do not use sliding scale insulin as the sole treatment for hospitalized patients—use scheduled basal-bolus regimens instead 1

Metformin Pitfalls to Avoid

• Taking metformin with or after meals reduces its glucose-lowering efficacy and eliminates the GLP-1 stimulation benefit 6
• The common practice of taking metformin "with meals" to reduce gastrointestinal side effects may compromise glycemic control 6