Feasibility of a New Approach to Initiate Insulin in Type 2 Diabetes

Abstract

Background: Treatment inertia and prescription complexity are among reasons that people with type 2 diabetes (T2D) do not reach glycemic targets. This study investigated feasibility of a new approach to basal insulin initiation, where the dose needed to reach a glycemic target is estimated from two weeks of insulin and continuous glucose monitoring (CGM) data.

Methods: This was an exploratory single arm study with a maximum length of 84 days. Eight insulin naïve people with T2D, planning to initiate basal insulin, wore a CGM throughout the study period. A predetermined regime was followed for the first two weeks after which the end dose was estimated. The clinician decided whether to follow this advice and continued the titration until target was reached using a twice weekly stepwise titration algorithm. The primary outcome was the comparison between the estimated and the actual end doses.

Results: Median age of participants was 57 years (range: 50-77 years), duration of diabetes was 16 years (range: 5-29 years), and Bodi Mass Index (BMI) was 30.2 kg/m2 (range: 22.0-36.0 kg/m2). The median study end dose was 37 U (range: 20-123 U). The estimated end dose was smaller than or equal to the study end dose in all cases, with median error of 26.7% (range: 0.0%-75.8% underestimation). No self-monitoring of blood glucose values were below 70 mg/dL and no severe hypoglycemia occurred.

Conclusion: While accuracy may be improved, it was found safe to predict the study end dose of insulin degludec from two weeks of data.

Keywords: basal insulin; continuous glucose monitoring; degludec; dose response model; insulin initiation; type 2 diabetes.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.B.A., H.B., and M.L.J. are full- or part-time employees of Novo Nordisk A/S. K.N. serves as advisor to Sanofi, Medtronic, Abbott, and Novo Nordisk; owns shares in Novo Nordisk; has received research grants from Novo Nordisk and Roche Diabetes Care; and has received fees for speaking from Medtronic, Roche Diabetes Care, Rubin Medical, Sanofi, Novo Nordisk, Zealand Pharma, and Bayer. S.S. has served on advisory boards for Roche Diabetes Care and Medtronic.

Figures

Figure 1.

Overview of the study procedure. A predetermined regime was followed for the first two weeks. The dose prediction software suggested 75% of the estimated end dose. The clinician determined whether to follow this advice and continued the titration until target was reached. Titration continued twice weekly using a stepwise titration algorithm (−4 to +8 U steps) with target range of 72-108 mg/dL until the study end dose was achieved or until day 84.

Figure 2.

A concept illustration of the linear dose response model. The model assumed linear response of fasting glucose (x markers) to basal insulin. This model was used to estimate the end dose.

Figure 3.

Lowest daily average one-hour continuous glucose monitoring interval. The algorithm located the lowest average one hour of continuous glucose monitoring data of each day. This glucose level was used to determine the dose response to the basal insulin.

Figure 4.

A visualization of the primary outcome. Comparison of the estimated end dose to reach 6.0 mmol/L based on insulin data, and continuous glucose monitoring or SMBG data after two weeks, compared to the study end dose for the eight participants.

Figure 5.

Time in hypoglycemia (below 70 mg/dL), hyperglycemia (above 180 mg/dL), and normoglycemia (between 70 and 180 mg/dL) during the first and last four days of the study for the eight participants, as measured by percentage of continuous glucose monitoring data points in each range.