Hypoglycemia with New Generation Basal Analog Insulins: A Descriptive Critical Review

Mazen Alsahli James R Thrasher

doi:10.4172/2155-6156.1000576

Abstract

Optimizing the treatment of people with diabetes relies on balancing the benefits of glycemic control with the risk of hypoglycemia. Although insulin is essential for treating patients with type 1 diabetes mellitus (T1DM), patient and physician concerns regarding an increased risk of hypoglycemia can lead to delays in initiating insulin treatment in patients with type 2 diabetes mellitus (T2DM). This clinical inertia contributes to reduced glycemic control and poorer outcomes for patients. Advances in insulin agents have reduced the risk of hypoglycemia. In particular, the introduction of insulin glargine, the first basal analog insulin with a 24-hour glucose-lowering profile with no pronounced peak, represented a significant step towards achieving this goal. To further improve patient management, a number of insulin formulations and molecules are in development and are designed to have pharmacokinetic/pharmacodynamic (PK/PD) profiles allowing closer mimicking of normal physiologic insulin release. Here we review these new agents, and discuss their hypoglycemic risk as reported in clinical trials. In addition, the difficulties in making comparative evaluations from studies with different patient populations and definitions of hypoglycemia are discussed. Solutions to improve future clinical trials are suggested. In general, the improved PK/PD profiles of new generation insulins appear to result in better clinical outcomes in terms of hypoglycemia. What is needed are head-to-head trials using standardized methods and criteria to allow clinicians to compare hypoglycemia rates between insulins, and help them to discuss appropriate choices of therapy with their patients.

Highlights

Insulin treatment is essential for individuals with type 1 diabetes mellitus (T1DM)
We review the new generation of basal analog insulins in terms of their effect on hypoglycemia rates in clinical trials
The BEGIN Basal-Bolus trial was a 52-week, parallel-group, openlabel trial of patients treated with Insulin degludec (IDeg) or glargine 100 units/ml (Gla-100) QD plus mealtime insulin aspart, in which basal analog insulins were titrated with an aim of achieving blood glucose ~70-90 mg/dl (3.9-5.0 mmol/l) [47]

Summary

Introduction

Insulin treatment is essential for individuals with type 1 diabetes mellitus (T1DM). As a result of progressive beta-cell deterioration in type 2 diabetes mellitus (T2DM), most patients with T2DM eventually require insulin to achieve and maintain optimal glycemic targets. We review the new generation of basal analog insulins in terms of their effect on hypoglycemia rates in clinical trials. In a recent PK/PD study in patients with T2DM, the new insulin glargine LY2963016 was shown to have a similar profile to Gla-100, with a duration of action of approximately 24 hours [35]. The clinical use of Gla-100 is associated with a lower risk of hypoglycemia than NPH insulin; this is a result of its longer, more constant PK/PD profile and a reduction in the variability of glucose-lowering effects [19,20]. Data from clinical trials suggest that the newer generation of basal analog insulins, with their extended, smoother PK/PD profiles, may result in improved rates of hypoglycemia compared with currently available insulins. - Confirmed hypoglycemia (PG ≤70 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe*

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Conflicts of Interest