Insulin Strategies to Treat Type 2 Diabetes

Insulin is initiated as treatment of type 2 diabetes mellitus (T2DM) when lifestyle modifications and antiglycemic drugs fail to adequately reach treatment goals, when there are contraindications or intolerances to other diabetes treatments, when glucotoxicity is present, or to improve and preserve beta-cell function.¹ The progressive loss of beta-cell function in T2DM leads to the requirement for insulin therapy in the majority of patients.² Numerous strategies can be used when implementing insulin regimens; this may create a cumbersome clinical decision-making process for the health care provider.

Adding basal insulin is a simple approach to initiating insulin therapy in patients with T2DM, particularly as augmentation therapy. The starting dose of an intermediate- (neutral protamine Hagedorn, neutral protamine lispro) or long-acting insulin (detemir, glargine) is generally 10 units or 0.1 to 0.2 units/kg daily.^1,3 The dose can be increased by 1 to 2 units for every 20 mg/dL the fasting blood glucose is over 100 mg/dL. Ideally, titrations should occur once or twice weekly.^3,4 A dose reduction of 2 to 4 units is advisable if hypoglycemia occurs.^1,3 Clinical judgment should be exercised in determining which patients can be taught to self-titrate the insulin dose and which patients require practitioner-directed dose adjustments. Regardless, the clinician and the patient should have frequent contact until a stable dose is determined.

Fasting Always Comes First
Remember to “fix the fasting first.” Treating to get fasting blood glucose levels to goal will reduce the degree of postprandial hyperglycemia.⁵ If insulin detemir or an intermediate-acting insulin is used, a second injection may be added in the morning, titrated based on the pre-dinner blood glucose level.⁶ Prandial or bolus insulin should be considered when the HbA_1C level is above goal and fasting glucose control has been achieved, or when the daily basal insulin dose approaches 1 unit/kg.¹ A rapid-acting insulin analogue can be added before the largest meal of the day or before the meal noted to be responsible for the largest increase in blood glucose level. Bolus insulin can be initiated at 4 units and titrated by 2 units every 3 days until goal preprandial or postprandial glucose levels are reached. Adding a second or third bolus insulin injection before other meals may be warranted if the HbA_1C level continues to be elevated.⁷

Premixed insulins should be used with caution. These formulations offer less flexibility in the timing of insulin administration, diet, and lifestyle. Hypoglycemia and weight gain are more common with premixed insulin than with basal-bolus regimens.⁸ Titration becomes difficult, because any modification to the dose will change the amount of both basal and bolus insulin the patient receives.

Ideally, metformin is continued when insulin is initiated. Less weight gain and lower insulin doses are required with combination therapy. To reduce the risk of hypoglycemia, sulfonylureas should be discontinued when basal-bolus insulin regimens are used. Thiazolidinediones (TZDs) can increase weight gain and edema when used with insulin. Thus, discontinuing the TZD or reducing the dose should be considered.¹ Combination basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists appears to be a promising treatment strategy. The benefits observed with the combination include improved postprandial glucose control and weight loss without an increased risk of hypoglycemia.⁹

The initiation of insulin can be a daunting task for both the patient with T2DM and the clinician. It is prudent to use a simple strategy for insulin implementation, which in the majority of patients is a once-daily basal insulin regimen.

References

1. Inzucchi SE, Bergenstal RM, Buse JB, et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-1379.

2. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281:2005-2012.

3. Riddle MC, Rosenstock J, Gerich J; Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26:3080-3086.

4. Mooradian AD, Bernbaum M, Albert SG. Narrative review: a rational approach to starting insulin therapy. Ann Intern Med. 2006;145:125-134.

5. Carroll M, Izard A, Riboni K, et al. Fasting hyperglycemia predicts the magnitude of postprandial hyperglycemia: implications for diabetes therapy. Diabetes Care. 2002;25:1247-1248.

6. Rosenstock J, Davies M, Home PD, et al. A randomized, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia. 2008;51:408-416.

7. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes [published correction appears in Diabetes Care. 2006;29:2816-2818]. Diabetes Care. 2006;29:1963-1972.

8. Ampudia-Blasco FJ, Rossetti P, Ascaso JF. Basal plus basal-bolus approach in type 2 diabetes. Diabetes Technol Ther. 2011;13(suppl 1):S75-S83.

9. Perfetti R. Combining basal insulin analogs with glucagon-like peptide-1 mimetics. Diabetes Technol Ther. 2011;13:873-881.