Treatment of Type 2 Using Insulin

Summary

A major component of the overall glycemic burden to which patients are exposed reflects the delay in adjusting therapy to meet the increasing requirement for intervention over time—the average patient accumulates up to 10 years of glycemic burden (HbA_1c of more than 7%) before insulin is commenced. An urgent change in the approach to glucose-lowering treatment is clearly required. Because of the overwhelming evidence in support of glycemic control and an awareness of the long-term consequences of hyperglycemia, in particular the onset and progression of vascular (micro- and macrovascular) complications, insulin therapy is increasingly seen as a key intervention in type 2 diabetes mellitus (T2DM).

Although the rationale is strong and the evidence clearly justifies the early use of insulin, issues of implementation and overcoming barriers to utilise/introduce insulin remain critical. The recent comparative data between the third National Health and Nutrition Examination Survey (NHANES III) (1988–1994) and the latest NHANES (1999–2000) strongly support this view. The report reveals certain changes in the pattern of insulin use in the USA, with a fall in the use of insulin monotherapy (24 to 16%) and an increase of insulin plus oral agents (3 to 11%) (Koro CE et al. Diabetes Care 27: 17–20, 2004), but the total usage of insulin remained relatively unchanged. Of note, these data do not however reflect the emerging paradigm of early insulin replacement when combination oral agents fail to maintain blood glucose within defined glycemic targets that has gained force over the last 5 years.

Of momentum central concern for physicians and persons with T2DM is the requirements relating to subcutaneous insulin injection. Historically, insulin therapy was viewed as reflecting the final stage of the disease, with all the negative connotations associated with this clinical situation/scenario and that, with insulin, increased side effects could be expected. The patient’s concern is the introduction of often compounded by the physician’s reluctance to initiating insulin therapy and thereby, very often, sub-optimal glycemic control persists as the way forward. What is frequently lacking in these cases is a clear educational message to patients of the benefits of insulin. Looking to the ongoing outcome trials, if these studies provide convincing evidence in terms of cardiovascular event reductions, the task of persuading physicians and patients of the need for early insulin replacement as an expected strategy to achieve near-normoglycemic control will be made a lot easier. Furthermore, it may be demonstrated in these trials that the early introduction of near physiologic insulin replacement within a “window of opportunity” is critical for retaining β-cell function, which will in turn facilitate long-term maintenance of glycemic control. Whilst this remains to be proven, patient education remains a key in advancing the message of insulin benefit.

Major advances in insulin therapy include changes in the different formulations of insulin available and in how insulin can be delivered. The advent of long-acting insulin analogues for early basal replacement and rapid-acting insulin analogue or inhaled insulin for progressive prandial replacement can have a major impact as the necessary tools for health care providers to empower patients to take charge of their own diabetes control along with self blood glucose monitoring. Inhaled insulin may offer the best opportunity yet to advance insulin treatment in T2DM by removing the need for injections in the initial stage of the disease.

Basal insulin provision is intended to inhibit hepatic glucose production in an attempt to normalize fasting blood glucose. When normalization is achieved, but the HbA_1c remains above the defined HbA1c target of 7%, attention should then be focused on assessing and correcting the postprandial glucose excursions. This approach is very simple to understand by health care providers, to “fix fasting first,” and then an escalation of therapy to include prandial insulin as required when the HbA_1c exceeds 7%, only when basal insulin therapy has already been optimized whilst avoiding hypoglycaemia. In those patients with well controlled fasting glucose <100 mg/dL, it is the postprandial glucose excursions that are the predominant factor in the glycemic burden, (Monnier et al. 2003, 2007) and proper intervention with prandial insulin can further improve glycemic control. Alternatively, patients who have maximized oral agent therapy and the HbA_1c marginally exceeds 7%, perhaps in the 7–8% range, may find the option of starting first with inhaled insulin very attractive especially if the long-term safety data are convincing and glycemic targets can be sustained overtime with inhaled insulin. Basal insulin replacement will then be eventually added if the HbA_1c remains >7%, especially if the FPG is >100 mg/dL.

The current treatment debate in T2DM is not about insulin, but when and how to introduce simple insulin regimens, dictated by clear algorithms and driven by blood glucose monitoring to achieve long-term near-normoglycemia with minimal effort, and initiated and managed by the particular in partnership with the diabetes care team. Clearly, patients should not be left with excess glycemic burden for extended periods and an aggressive strategy to maintain glycemic control with early insulin introduction to ensure target levels of glycemia will bring well being to the patient and counter the dreaded long-term complications of diabetes.