Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin‐pump‐treated patients with type 1 diabetes: The Lira Pump trial—a randomized, double‐blinded, placebo‐controlled trial

Abstract

Aim To investigate the efficacy of adding the glucagon‐like peptide‐1 receptor agonist liraglutide to continuous subcutaneous insulin infusion (CSII) in overweight or obese persons with type 1 diabetes and non‐optimal glycaemic control. Materials and methods A 26‐week, randomized, double‐blind, placebo‐controlled trial including 44 overweight or obese adults with type 1 diabetes randomized 1:1 to liraglutide 1.8 mg once daily (QD) or placebo added to CSII treatment. The primary endpoint was change in haemoglobin A1c (HbA1c). Secondary endpoints included change in insulin dose, CSII settings, glycaemic variability, body weight and patient‐reported outcome measures. Finally, adverse effects including hypoglycaemic events were registered. Results HbA1c was reduced by 5 mmol/mol (0.5%) from a baseline of 66 mmol/mol (8.2%) in patients treated with liraglutide compared with a non‐significant change of +2.3 mmol/mol (0.2%) from a baseline of 66 mmol/mol (8.1%) in patients treated with placebo (between‐group difference 7 mmol/mol [0.7%], P < 0.001). Liraglutide reduced total insulin dose by 8 units/day or 16% of total insulin dose (P = 0.008). Mean body weight was reduced by 6.3 kg (P < 0.001) compared with placebo. Concomitantly, time spent in glycaemic target range 4–10 mmol/L (71–180 mg/dL) increased while the risk of hypoglycaemia did not differ between groups at the end of treatment. Conclusion Liraglutide treatment reduced HbA1c, total daily insulin dose and body weight without increasing the risk of hypoglycaemia in CSII‐treated patients with type 1 diabetes and insufficient glycaemic control. Liraglutide may be considered a potential add‐on therapy to insulin in this subgroup of patients.

Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the ADJUNCT ONE and ADJUNCT TWO randomized controlled trials

“…Moreover, despite the finding that the incidence of hyperglycaemia with ketosis observed in both trials was numerically higher with liraglutide than with placebo, the risk of DKA was very low with all doses of liraglutide As delineated above, it should be noted that several smaller trials have added to the evidence of the effects of liraglutide in people with type 1 diabetes. [11][12][13][14][15][16][17][18][19] The investigations have unanimously found no major safety concerns, including no increased risk of hypoglycaemia, and a meta-analysis has reported a lower risk of hypoglycaemia with liraglutide than with placebo. 11 Furthermore, no evidence has been reported to indicate increased risks of ketosis-accompanied hyperglycaemia or DKA with liraglutide, corroborating the results from the ADJUNCT trials.…”

GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art

“…in addition to intensified insulin regimens, however, did not demonstrate convincing benefits (e.g., with respect to optimized glycemic control or the frequency of hypoglycemic episodes) or described potential adverse outcomes such as a higher risk of ketoacidosis. Only body weight and insulin doses were consistently reduced [ [194] , [195] , [196] , [197] ]. However, these results do not rule out benefits for specific subgroups (e.g., obese patients with type 1 diabetes or subjects at high risk of cardiovascular complications) or with dosage recommendations that may differ from those used to treat type 2 diabetes.…”

Strategically Playing with Fire: SGLT Inhibitors as Possible Adjunct to Closed-Loop Insulin Therapy

“…29 Glucagon-like Peptitde-1 (GLP1)-receptor agonists have demonstrated conflicting outcomes in benefits as adjunct to T1D care, both with and without HCL. 24-27,30-33 The effect of dipeptitdyl peptidase-4 inhibitors is not as significant compared to other adjunctive agents in T1D, 34 with one inpatient study demonstrating reduced post-prandial glycemia with sitagliptin using HCL. 27 While pramlintide has been studied as an injectable pharmacotherapy adjunct to routine insulin therapy or integrated into HCL, 19,24,25 and has shown benefits, 22,24 its clinical application is limited by the lack of an existing co-formulation with insulin and the need for separate injections or infusion systems.…”