Strategies for initiating insulin in type 2 diabetes

Clinical question

What is the optimal regimen for initiating insulin in type 2 diabetes (T2D)?

Evidence

Four reasonably sized randomized controlled trials address initiating insulin in T2D with poor glucose control.

• The 4-T study¹ followed 708 patients for 3 years, comparing long-acting basal insulin once daily, biphasic mixed insulin twice daily, and prandial insulin with meals.¹

  • -Levels of glycated hemoglobin A_1c (HbA_1c) were not significantly different among the 3 groups.

    • —Significantly more patients in the basal and prandial groups attained HbA_1c levels ≤ 7.0% (63% and 67%, respectively, vs 49% biphasic; P < .001).

  • -Those taking basal insulin had significantly (P < .05) ...

    • —less weight gain (3.6 kg) than patients using prandial (6.4 kg) or biphasic insulin (5.7 kg),

    • —fewer confirmed symptomatic hypoglycemic events per year (1.7 basal vs 3.0 biphasic vs 5.7 prandial), and

    • —higher total doses of insulin than biphasic patients.

  • -More patients using basal insulin (82%) also required a second type of insulin (vs 74% prandial, 68% biphasic).

• The 3 other studies^2–4 followed 160 to 418 patients (total 811) for 6 months to 1 year and compared basal with prandial,² basal with biphasic,³ and biphasic with prandial⁴ insulin.

  • -Levels of HbA_1c were generally similar, except biphasic insulin improved HbA_1c 0.5% more than basal insulin in 1 study and got more people to HbA_1c levels ≤ 7.0%.³

  • -Basal insulin had significantly less hypoglycemia than prandial (P < .001)² or biphasic (P < .05)³ insulin and less weight gain than biphasic (P < .01)³ insulin.

Context

• The 4-T study¹ is given priority because it is the largest and longest and compares the 3 options. Fortunately, the remaining studies^2–4 generally support those findings.

• INSIGHT⁵ found initiating basal insulin in poorly controlled T2D resulted in significantly lower HbA_1c levels than continued oral hypoglycemic agents did (P = .005).

  • -Mean HbA_1c levels and rates of hypoglycemia were not different between patients of FPs and diabetes experts.⁶

• Specialists are 5 times more likely to initiate insulin.⁷

Bottom line

In T2D poorly controlled with oral agents, initiating basal insulin results in similar HbA_1c reductions compared with prandial or biphasic insulin and might cause less weight gain and hypoglycemia. Family physicians who start insulin are as effective as specialists.

Implementation

While newer insulin products have theoretical advantages, a meta-analysis found that compared with neutral protamine Hagedorn (NPH), longer-acting insulin offers little or no benefit but costs much more.⁸ Advantages from reductions in hypoglycemia are at high risk of bias.⁹ To initiate basal insulin, prescribe NPH, 10 units daily at bedtime, increasing by 1 unit each night until fasting blood glucose is 4 to 7 mmol/L, remembering to educate the patient about hypoglycemia.¹⁰ A printable document available online simplifies the process of prescribing insulin¹¹: www.ocfp.on.ca/local/files/InsulinPrescription_Rev1.pdf.