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 AE 2.6 vs 8.8 AE 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 AE 2.3 vs 8.7 AE 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 AE 2.6 vs 9.2 AE 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 AE 3.3 vs 3.1 AE 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.The association between hyperglycaemia and poor clinical outcomes in patients with and without diabetes is well established. 1-5 Extensive data from observational and prospective randomized controlled trials in hospitalized patients have resulted in a strong association between hyperglycaemia and poor clinical outcomes, such as increased mortality, morbidity, length of hospital stay (LOS), infections and overall complications. 1,4,6-8 Most clinical trials in critically ill and in noncritically ill medicine and surgery patients with hyperglycaemia and diabetes have reported that improved glycaemic control reduces LOS, risk of multi-organ failure and systemic infections, 9-12 as well as short-and long-term mortality, 6,11 although the largest trial in critically ill patients showed increased mortality with intensive glucose control. 12 Current clinical guidelines from professional societies recommend basal-bolus insulin regimens as the standard of care for hospitalized patients with type 2 diabetes (T2D). 13,14 Our group has shown that a basal-bolus insulin regimen resulted in improved glycaemic co...

Sitagliptin for the prevention and treatment of perioperative hyperglycaemia in patients with type 2 diabetes undergoing cardiac surgery: A randomized controlled trial

“…In addition to iatrogenic hypoglycaemia, the significant workload associated with continuous insulin infusion and multiple daily insulin injections has led to an increased use of non‐insulin agents to manage patients with diabetes in hospital 27 . As an alternative to intensified insulin regimens, our group and others have reported on the use of DPP‐4 inhibitors for the management of inpatients with diabetes 15,16,27,28 . Recent RCTs have reported that treatment with DPP‐4 inhibitors alone or in combination with basal insulin in general surgery patients results in improved glycaemic control with a lower risk of hypoglycaemia compared with a basal bolus insulin regimen 15,16,28 .…”

15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2021

“…The safety and efficacy of noninsulin glucose-lowering therapies in the hospital setting is an area of active research (57,58). Several recent randomized trials have demonstrated the potential effectiveness of glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors in specific groups of hospitalized patients (59)(60)(61)(62). However, an FDA bulletin states that providers should consider discontinuing saxagliptin and alogliptin in people who develop heart failure (63).…”

Inpatient Hyperglycemia Management and COVID-19

“…There are limited data available about the efficacy and safety of non-insulin agents in hospitalized patients, almost restricted to dipeptidyl peptidase 4 (DPP4) inhibitors [40][41][42][43][44]. These agents in combination with basal insulin may represent an alternative in patients with COVID-19 and mild to moderate hyperglycemia [33].…”