Participants and Baseline Characteristics
A total of 126 individuals were screened and 120 were included in phase I (Fig. 1). At week 12, 110 study subjects had achieved FBG ≤6.5 mmol/L, of whom 66 did not achieve HbA1c ≤7% and were therefore included in phase II. Of the 66 patients included in phase II, three withdrew due to either patient dissatisfaction with treatment outcome (n = 1), accidental injury (n = 1), or personal reasons (n = 1).
At baseline, the mean age of the study subjects was 59.3 (8.7) years, 53.3% were female, and the mean duration of T2DM was 6.6 (2.4) years. The mean dose of basal insulin was 0.22 IU/kg/day, and 98.3%, 56.7%, and 74.2% of subjects were receiving concomitant α-glucosidase inhibitors, metformin, and insulin secretagogues, respectively (Table 1). At baseline, mean levels of HbA1c, FBG, and PBG were 8.83%, 9.28, and 14.47 mmol/L, respectively.
Basal Insulin Optimization from Baseline to Week 12
After 12 weeks of basal insulin optimization, the mean basal insulin dose had significantly increased from 0.22 IU/kg/day at baseline to 0.36 IU/kg/day (p < 0.001) (Table 1). Between baseline and week 12, a significant decrease in mean HbA1c (−1.43%), FBG (−3.04 mmol/L), and PBG (−3.58 mmol/L) was observed (all p < 0.001) (Fig. 2a and b). However, the mean weight and BMI of the study subjects did not change significantly during the 12-week basal insulin optimization phase (Fig. 2c). Hypoglycemia was experienced by three patients during the basal insulin optimization phase (Table 1). The pattern of use of concomitant OADs did not change between baseline and week 12.
Basal Plus Prandial Insulin Treatment from Week 12 to Week 36
For study subjects who achieved FBG ≤6.5 mmol/L but did not reach HbA1c ≤7% after 12 weeks of basal insulin optimization, the addition of prandial insulin led to a significant reduction in HbA1c of 0.89%, with a mean HbA1c of 7.17% at week 36 (p < 0.001) (Table 2) (Fig. 3a). Furthermore, the mean FBG did not change, and PBG decreased significantly, by 3.03 mmol/L (p < 0.001), following 24 weeks of basal-plus therapy (Fig. 3b). The mean total dose of insulin at week 36 was 0.5 IU/kg/day. After initiating prandial insulin treatment, 83.1% of the patients receiving insulin secretagogues ceased using these drugs, and the mean number of OADs used also decreased from 2.71 to 2.12. The proportion of patients completing the 24 weeks of basal- plus treatment was 95.5% (63/66).
Three patients had symptomatic hypoglycemia events during the 24 weeks of basal-plus treatment. There was no significant difference in the incidence of hypoglycemia before and after treatment (1.7% vs. 2.5% χ
2 = 0.21; p = 1.000) (Table 2). No severe hypoglycemia or other severe adverse events were identified during this phase of the study. After 24 weeks of prandial insulin, the mean weight of patients increased slightly without reaching statistical significance versus week 12 (73.2 vs. 73.3 kg; p = 0.379) (Table 2) (Fig. 3c).
Baseline Characteristics of Patients Who Achieved HbA1c ≤7% Versus Those Who Did Not
The proportion of patients who completed 24 weeks of basal-plus therapy and achieved HbA1c ≤7% was 65.1% (41/63) (Table 3). Mean baseline HbA1c level, FBG level, and PBG level were significantly higher among the study subjects who did not achieve HbA1c ≤7% than among those who did achieve this target (differences: 0.94%, 1.08, and 2.48 mmol/L, respectively; all p values <0.05) (Table 3). No significant difference in baseline age, disease course, duration of insulin use, baseline insulin dose, weight, height, BMI, or use of OADs was observed between patients who achieved HbA1c ≤7% and those who did not.
Multiple Linear Regression of Factors Associated with HbA1c at Week 36
In a stepwise multiple linear regression, baseline HbA1c (B = 0.18, p = 0.022), PBG (B = 0.15, p < 0.001), and FBG (B = 0.08, p = 0.027) were significantly associated with HbA1c at the end of phase II (Table 4).