Treat-to-target insulin titration algorithms when initiating long or intermediate acting insulin in type 2 diabetes

Abstract

Background: Until recently, titration of insulin in type 2 diabetes clinical trials was typically left up to the investigator's discretion with a simple statement of the target ranges for glucose. In type 2 diabetes trials the average glycemic control achieved was usually less than desirable. Since then a number of trials have been conducted and reported utilizing various algorithms under various conditions. The objective of this article is to provide a review of the evidence to date.

Methods: In addition to studies already identified through work in the area, the literature was searched using PubMed with the search words "insulin and titration" and subsequently "insulin and algorithm" from which studies starting insulin therapy using insulin titration algorithms in type 2 diabetes were selected.

Results: The different algorithms and achieved results for glycemic control and hypoglycemia, as well as factors appearing to impact the results, are reviewed.

Conclusion: The recent introduction of rigorously implemented insulin titration algorithms when adding on basal insulin to oral drugs in inadequately treated type 2 diabetes patients has led to better average glycemic control with little risk of severe hypoglycemia, as long as the morning fasting plasma glucose target is not lower than 100 mg/dl. Insulin titration algorithms have undergone and continue evolution in the direction of increased patient control.

Keywords: FPG; NPH; algorithm; basal; detemir; fasting glucose; glargine; insulin; severe hypoglycemia; titration.

Figure 1.

Insulin titration steps given average self-monitored morning FPGs in key studies. The left were designed for weekly titration minimally in the beginning of the studies, the next group for titration every 2 to 3 days, and the final on the right for daily titration. The studies are displayed from left to right roughly in the temporal sequence of trial implementation consistent with the algorithm evolution with the one notable exception of the AT.LANTUS trial patient algorithm that is placed further to the right with the every 2–3 days.

Figure 2.

Insulin dose (a), FPG (b), and HbA1c (c) achieved as a function of morning FPG target. Squares: studies with a target range, but no specific prescribed insulin dose adjustments. X: studies with insulin dose algorithms, but left to the investigator's discretion to follow. Triangles: studies with insulin dose algorithms and centralized oversight over adherence. Diamonds: studies with insulin dose algorithms adjusted by the patient, but under tight clinic supervision. Circles: studies with insulin dose algorithms adjusted by the patient with minimal clinic supervision.