Taking the stress out of insulin initiation in type 2 diabetes mellitus

Case

Tom is a 72-year-old man who has type 2 DM, hypertension, hyperlipidemia, and stable angina. He has had type 2 DM for about 14 years; until recently, his blood glucose (BG) levels were well controlled with combinations of oral hypoglycemic agents (OHAs), diet, and regular exercise. Over the past year his glycosylated hemoglobin A_1c (HbA_1c) levels have climbed; last month they were measured at 9.2%. This translates to an estimated average glucose (eAG) level of 12.1 mmol/L.4 Recent self-monitored BG readings include the following: fasting 8.9 to 11.2 mmol/L; before lunch 7.8 to 9.2 mmol/L; 1 hour after lunch 10.9 to 13.4 mmol/L; before supper 9.9 to 10 mmol/L.

Current diabetes medications include 1000 mg of metformin twice daily, 30 mg of pioglitazone daily, and 60 mg of gliclazide daily. He is taking optimal therapy for cardiovascular protection, including blood pressure control and statin therapy, which have proven outcome benefits.

In the clinic, you review Tom’s recent HbA_1c and BG values; he informs you that he is following the diet guidelines recommended by the dietitian 6 months ago and is exercising for 30 to 60 minutes most days. A recent 2-kg weight loss confirms Tom’s lifestyle management progress. Tom asks you, “What else can I do to improve my blood sugars?”

While it is tempting to avoid the “inconvenience” of initiating insulin therapy at this clinic visit, it might be the preferred option for pursuing glycemic control. Tom is already taking adequate doses of 3 classes of OHAs.5 Further dose increases are unlikely to result in substantial reduction in glucose levels and might increase his risk of side effects. Sitagliptin could be considered, given its postprandial effect and minimal weight gain; however, it lacks outcome evidence and long-term safety data and reduces HbA_1c by only about 0.7%.6 There is no evidence supporting its role as an add-on therapy to 3 other classes of OHAs.

Type 2 diabetes is characterized by insulin resistance and progressive decline in pancreatic β-cell function and endogenous insulin production.1 Physicians and patients need to acknowledge the progressive nature of type 2 DM and make appropriate advances in diabetic therapy (diet and lifestyle → OHAs → insulin). Because he has had type 2 DM for 14 years, Tom’s pancreas might not be able to produce adequate amounts of insulin even with additional OHA therapy. Thus insulin is an appropriate step-up therapy.

Successful initiation of insulin might be facilitated by the following considerations7,8:

• Explain the rationale for starting insulin, emphasizing the progressive nature of type 2 DM and not blaming the patient. A demonstration of how insulin injections can be easily administered with a pen device allays many fears and misconceptions that people have about insulin, needles, and syringes (Box 19).

• To avoid large drops in BG levels and ensure patient adherence, start with a low dose of basal insulin (eg, intermediate-acting insulin) at 5 to 10 units or 0.1 to 0.2 units/kg total body weight at bedtime. Give the patient written instructions on titrating the dose (eg, increase by 2 units every 3 days until fasting glucose < 7 mmol/L).1 Avoid dosage increases if the patient experiences nocturnal hypoglycemia or 2 or more episodes of BG levels below 4 mmol/L.

• Contact the patient’s pharmacist or diabetes educator and ask him or her to provide instruction on use of the insulin delivery device and dosage adjustment if you are not able to do this in your practice.

• Metformin therapy should generally be continued when initiating insulin if it is not contraindicated (eg, in acute heart failure). Metformin has outcome evidence for reduced mortality, results in less weight gain from insulin, and might decrease the required insulin dose.10,11 Thus metformin can be continued even with multiple daily insulin injection regimens. Caution and dose reduction are required in patients with moderate renal impairment (creatinine clearance 30 to 60 mL/min).1,2

• Sulfonylureas (eg, gliclazide) might contribute to glycemic control when once-daily basal insulin is used, but should usually be discontinued if mealtime short-acting or rapid insulin is added. Thiazolidinediones (eg, pioglitazone, rosiglitazone) are not approved for use with insulin and are usually discontinued owing to the increased risks of edema, heart failure, and weight gain.12,13

• Hypoglycemia is rare in patients with type 2 DM taking combinations of metformin and basal intermediate- or long-acting insulin. However, all patients using insulin should learn the risks, symptoms, and treatment of hypoglycemia.1,7

• Self-monitoring of BG needs to be individualized.1,7 Type 2 DM patients taking insulin will need to monitor BG more frequently. Preprandial and postprandial BG levels are required to decide if and when to start mealtime insulin therapy.

• Individualize treatment goals balancing uncertain benefits with potential risks and difficulties of tighter glucose control.1,14

Most patients with type 2 DM have few problems with insulin therapy when it is started once daily in addition to metformin. Once comfortable with basal insulin therapy, they are more willing to accept the introduction of bolus (short-acting or rapid) insulin (Table 18) before meals for better postprandial glycemic control.1,2

There is some debate about the role of long-acting insulin analogues (LAIAs) in the initiation of basal insulin therapy in patients with type 2 DM. While some authors suggest a prominent role, recent systematic reviews have found that LAIAs offer little advantage over neutral protamine Hagedorn (NPH) for initial therapy.15–18 The primary advantage of LAIAs is the potential for less nocturnal hypoglycemia in some patients; HbA_1c and weight end points are similar to those seen with intermediate-acting insulin15,16 and outcome evidence is lacking. Newer LAIAs cost more than twice as much as intermediate-acting insulin (Table 18). Further advantages and disadvantages of the different types of insulin are outlined in Table 2.15–22