A Randomized Controlled, Treat-to-Target Study Evaluating the Efficacy and Safety of Insulin Glargine 300 U/mL (Gla-300) Administered Using Either Device-Supported or Routine Titration in People With Type 2 Diabetes

Abstract

Background: The efficacy/safety of device-supported versus routine titration with Gla-300 in type 2 diabetes (T2DM) was evaluated.

Method: AUTOMATIX was a 16-week, randomized, open-label, parallel-group, multicenter, noninferiority trial in insulin-treated or insulin-naïve people with T2DM. The fasting self-monitored plasma glucose (FSMPG) target was 90-130 mg/dL (5.0-7.2 mmol/L). Primary endpoint: proportion of participants achieving target FSMPG at week 16 without severe hypoglycemia. Secondary endpoints included: proportion reaching FSMPG target without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia; time to first achieve FSMPG target; mean FSMPG and HbA1c change (baseline to week 16). Safety endpoints included hypoglycemia and adverse events. Patient-reported outcomes (PROs) were also assessed.

Results: Participants were randomized to device-supported (n = 75) or routine titration (n = 76); 17 participants in the device-supported group discontinued device use. Noninferiority was achieved for the primary endpoint (device-supported: 45.9%, routine: 36.8%; weighted difference: 9.04 [95% CI: -6.75, 24.83]), but not superiority (P = .262). The proportion reaching FSMPG target range without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia was 34.3% vs 14.5%, respectively. The time at which 50% of the participants achieved the FSMPG target was less in the device-supported than routine titration arm (10 vs 13 weeks). Least squares mean HbA1c reduction, safety profiles, and PROs were similar in both arms. Mean "ease of use" score for the device, assessed by healthcare professionals and participants on a scale of 1-7, was ≥6.

Conclusions: Device-supported self-titration had a good safety/efficacy profile, and was noninferior to routine titration and well accepted by diabetes specialists and patients.

Keywords: basal insulin; blood glucose meter; hypoglycemia; titration.

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: MD—Advisory board: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Sanofi, Servier; Consultant: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi; Speaker’s bureau: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Takeda, Tanabe; Research support: Boehringer Ingelheim, Janssen, Novo Nordisk. SB—Advisory panel: Sanofi, Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Merck, Johnson & Johnson; Research support: Novo Nordisk, Merck. GC—Advisory panel: Eli Lilly; Board member: Sanofi, Eli Lilly, Novo Nordisk, Boehringer Ingelheim; Consultant: AstraZeneca. FF—Employee: Sanofi; Stock/shareholder: Sanofi. HG—Employee: Sanofi; Stock/shareholder: Sanofi. MW—Employee: Sanofi; Stock/shareholder: Sanofi. CH—No conflicts of interest to declare. GV—Advisory panel: Sanofi; Consultant: Meteda. SE—Board member: Senseonics; Speaker’s bureau and advisory panel: AstraZeneca, Dexcom, Eli Lilly, MannKind, Merck, Novo Nordisk, Sanofi.

Figures

Figure 1.

Estimated percentage of participants achieving target FSMPG without hypoglycemia during the 16-week on-treatment period (modified intent-to-treat population). aEstimated proportion of participants was obtained using a multiple imputation method to address missing values in the mITT population. bEstimated weighted difference of proportions obtained by combining the difference in percentage, weighted by the randomization stratum of previous use of insulin (insulin naïve, insulin pretreated), between titration groups of all different imputed data sets.

Figure 2.

Mean change in FSMPG over the 16-week on treatment period (modified intent-to-treat population).

Figure 3.

Incidence (%) of participants experiencing ≥1 hypoglycemic event during the on-treatment period (safety population).