Lower Severe Hypoglycemia Risk: Insulin Glargine Versus NPH Insulin in Type 2 Diabetes!

Volume 14: 25-30 January 2008 Number 1

Lower Severe Hypoglycemia Risk: Insulin Glargine Versus NPH Insulin in Type 2 Diabetes!

George Dailey, MD; and Poul Strange, MD

Hypoglycemia is a common consequence of achieving tight glycemic control for patients
with type 2 diabetes, with clinical effects ranging from occasional mild discomfort to incapacitation, coma, or in rare cases, death. Severe hypoglycemic events, particularly those resulting in emergency medical intervention or hospitalization, incur substantial medical costs for patients and the healthcare system. Although vigilance is needed for the possibility of severe events, hypoglycemia need not be a barrier to effective glycemic control in type 2 diabetes. Data from clinical trials and meta-analyses have demonstrated that the basal insulin analog insulin glargine results in a reduced rate of severe hypoglycemic events compared with conventional insulin therapy such as neutral protamine Hagedorn (NPH) insulin. Overall, use of insulin glargine compared with NPH insulin appears to reduce the risk of nocturnal and severe hypoglycemia by 40% to 60% and may result in cost savings. Analyses of hypoglycemia rates from “real-world” clinical practice databases and retrospective analyses of medical claims data also have revealed reduced rates with insulin glargine, consistent with the findings from clinical trials.

(Am J Manag Care. 2008;14:25-30)

Recommendations for Improving Adherence to Type 2 Diabetes Mellitus Therapy— Focus on Optimizing Insulin-Based Therapy

Understanding Type 2 Diabetes Mellitus and Associated Cardiovascular Disease: Linked by Insulin Resistance

The Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease: Understanding the Role of Insulin Resistance

Cost-Effectiveness of Insulin Analogs

Estimated Coronary Heart Disease Attributable to Insulin Resistance in Populations With and Without Type 2 Diabetes Mellitus

An abundance of data demonstrates that intensive glycemic control can preclude or delay chronic complications of diabetes.^1-6 Accordingly, intensive diabetes therapy that targets near-normal blood glucose levels is recommended by the American College of Endocrinology/American Association of Clinical Endocrinologists and the American Diabetes Association.^7,8 Iatrogenic hypoglycemia is an expected and common consequence of this approach to tight glycemic control.⁹

Because of the progressive decline in β-cell function in type 2 diabetes, for many patients insulin therapy will be essential to achieve and maintain glycemic control.^10,11 Although hypoglycemia during insulin therapy has been noted to be “less of a risk in type 2 diabetes compared with type 1 diabetes,” ⁷ it remains a common concern and can be a major barrier to both initiating and/or advancing insulin therapy.¹² Severe hypoglycemia is generally acknowledged to occur at about one tenth the rate of that in patients with type 1 diabetes who are treated to comparable glycosylated hemoglobin (A1C) levels with multiple daily insulin injections. Basal insulin glargine has demonstrated a lower risk of hypoglycemic events compared with neutral protamine Hagedorn (NPH) insulin in several clinical trials and thus is an important option for overcoming the barrier of hypoglycemia. This difference in hypoglycemic risk between insulin glargine and conventional insulin also has been examined in clinical practice database studies. Another basal insulin analog, insulin detemir, recently was introduced in the United States, although it has been marketed in Europe for more than 2 years. It also appears to have a significantly lower risk of causing hypoglycemia compared with NPH insulin in patients with type 2 diabetes.^13,14 At the time of this writing there were no published medical claims data or data from US clinical practice settings for insulin detemir; however, it will be important to examine these data as they become available.

We provide a brief overview of hypoglycemia in patients with insulintreated diabetes and focus on the incidence of hypoglycemia associated with insulin glargine in patients with type 2 diabetes in both research and practice settings. Data sources include randomized trials comparing insulin glargine to NPH insulin, clinical practice databases, and medical claims analyses.

OVERVIEW OF HYPOGLYCEMIA
Definitions and Incidence
Clinical hypoglycemia ranges from mild/moderate events that are easily recognized and reversed by the patient to severe, debilitating events that may require hospitalization. (For a review of hypoglycemia, see Hypoglycemia, Pathophysiology, Diagnosis, and Treatment.⁹) Nocturnal hypoglycemia is a common concern, with frequencies of >10% to ~50% reported in the literature (in patients with insulintreated diabetes^15-17). Severe (or “major”) events, although relatively uncommon, can cause sufficient patient impairment to necessitate intervention or support from another person.¹⁸ In the extreme, severe hypoglycemic events can lead to neurologic impairment and, in rare but serious cases, seizures, coma, and death.¹⁹

Comparisons of events across clinical trials can be a challenge because of differences in ascertainment, reporting measures, and methods. Severe hypoglycemia in insulin-treated patients with type 2 diabetes has been explored in both retrospective and prospective studies and has been reported most often as either an incidence rate or a percentage of patients experiencing 1 or more hypoglycemia events per year.²⁰ In general, the incidence of severe hypoglycemia was lower in prospective studies (0-20 episodes per 100 patient-years) than in retrospective studies (15-73 episodes per 100 patientyears). One of the largest ongoing prospective studies—the United Kingdom Prospective Diabetes Study—recently reported an annual rate of recurrent moderate or severe hypoglycemia of 3.8% to 5.5% in insulin-treated patients with type 2 diabetes.²¹ The differences in reported frequency of hypoglycemia between studies may be due to differences in clinical characteristics (eg, age), classification of “severe” episodes, risk-factor profiles, type of insulin regimen and intensity of treatment, duration of illness, and duration of insulin exposure.²⁰ In fact, during the first 2 years of insulin therapy, severe hypoglycemia rates are low (similar to rates in patients taking sulfonylureas), and hypoglycemic events are considerably less frequent than they are in patients with type 1 diabetes.¹¹ Furthermore, the rate of severe hypoglycemia in patients with type 2 diabetes has been estimated to be 10% of that in patients with type 1 diabetes, even with intensive insulin therapy.²²

Economic Burden
In addition to causing adverse symptoms and, in some cases, morbidity, hypoglycemia results in significant medical expenditures.^23-25 Moderate to severe hypoglycemia contributes to an increased use of healthcare services by insulintreated patients, including hospitalization, emergency room and office visits, and increased short-term disability leave.^23,24 Researchers who recently assessed the economic effects of hypoglycemia estimated a mean cost per episode of $1186 and annualized costs of $3241 per patient with a diagnosis of hypoglycemia.^23,24 Therapies that can provide effective glycemic control with less potential for hypoglycemia may be expected not only to improve medical outcomes, but also to help limit expenditures for healthcare.

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