Glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in patients with type 2 diabetes undergoing non-cardiac surgery: A multicentre randomized clinical trial

Abstract

Aims: The use of incretin-based therapy, rather than or complementary to, insulin therapy is an active area of research in hospitalized patients with type 2 diabetes (T2D). We determined the glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in hospitalized surgical patients with T2D.

Materials and methods: This prospective open-label multicentre study randomized T2D patients undergoing non-cardiac surgery with admission blood glucose (BG) of 7.8 to 22.2 mmol/L who were under treatment with diet, oral agents or total insulin dose (TDD) ≤ 0.5 units/kg/day to either linagliptin (n = 128) daily or basal-bolus (n = 122) with glargine once daily and rapid-acting insulin before meals. Both groups received supplemental insulin for BG > 7.8 mmol/L. The primary endpoint was difference in mean daily BG between groups.

Results: Mean daily BG was higher in the linagliptin group compared to the basal-bolus group (9.5 ± 2.6 vs 8.8 ± 2.3 mmol/L/dL, P = 0.03) with a mean daily BG difference of 0.6 mmol/L (95% confidence interval 0.04, 1.2). In patients with randomization BG < 11.1 mmol/L (63% of cohort), mean daily BG was similar in the linagliptin and basal-bolus groups (8.9 ± 2.3 vs 8.7 ± 2.3 mmol/L, P = 0.43); however, patients with BG ≥ 11.1 mmol/L who were treated with linagliptin had higher BG compared to the basal-bolus group (10.9 ± 2.6 vs 9.2 ± 2.2 mmol/L, P < 0.001). Linagliptin resulted in fewer hypoglycaemic events (1.6% vs 11%, P = 0.001; 86% relative risk reduction), with similar supplemental insulin and fewer daily insulin injections (2.0 ± 3.3 vs 3.1 ± 3.3, P < 0.001) compared to the basal-bolus group.

Conclusions: For patients with T2D undergoing non-cardiac surgery who presented with mild to moderate hyperglycaemia (BG < 11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy, resulting in similar glucose control with lower hypoglycaemia.

Keywords: DPP-IV inhibitor; glycaemic control; incretin therapy; randomised trial.

Figure 1:

Study Flow for the Randomized Controlled Study Comparing Linagliptin and Basal Bolus Insulin Regimen in Patients with Type 2 Diabetes undergoing non-cardiac surgery.

Figure 2:

Mean Daily BG Levels During Study Period in the Linagliptin and the Basal Bolus Insulin Regimens. Linagliptin (open bars) treatment was inferior to basal-bolus insulin (closed bars) treatment. Mean daily BGs were higher in the linagliptin group compared to basal-bolus group, p=0.03. After stratifying by randomization BG, there was no difference in mean daily glucose levels between the linagliptin and basal groups with randomization BG < 11.1 mmol/L. In patients with randomization BG ≥ 11.1 mmol/L, linagliptin group had higher mean daily glucose levels compared to basal bolus group, p<0.001. Data are expressed as mean ± SEM. Abbreviations: BG, Blood Glucose

Figure 3:

Mean BG Levels During Days on Study between Linagliptin and Basal Bolus Insulin Regimens. There were no differences in glucose levels on most days during the study between the linagliptin (open squares) and the basal bolus insulin regimen (closed circles) except on Day 3 of the study (p=0.03). Data are expressed as mean ± SEM. Abbreviations: BG, Blood Glucose