Liraglutide-Induced Weight Loss May be Affected by Autonomic Regulation in Type 1 Diabetes

The role of the autonomic nervous system in the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 1 diabetes is unknown. We assessed the association between autonomic function and weight loss induced by the GLP-1 RA liraglutide.Methods: Lira-1 was a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of 1.8 mg liraglutide once-daily for 24 weeks in overweight patients with type 1 diabetes. Autonomic function was assessed by heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio), to the Valsalva maneuver and resting heart rate variability (HRV) indices. Associations between baseline the cardiovascular autonomic neuropathy (CAN) diagnosis (> 1 pathological non-resting test) and levels of test outcomes on liraglutide-induced weight loss was assessed by linear regression models.Results: Ninety-nine patients with mean age 48 (SD 12) years, HbA1c 70 (IQR 66;75) mmol/mol and BMI of 30 (SD 3) kg/m2 were assigned to liraglutide (N = 50) or placebo (N = 49). The CAN diagnosis was not associated with weight loss. A 50% higher baseline level of the 30/15 ratio was associated with a larger weight reduction by liraglutide of −2.65 kg during the trial (95% CI: −4.60; −0.69; P = 0.009). Similar significant associations were found for several HRV indices.Conclusions: The overall CAN diagnosis was not associated with liraglutide-induced weight loss in overweight patients with type 1 diabetes. Assessed separately, better outcomes for several CAN measures were associated with higher weight loss, indicating that autonomic involvement in liraglutide-induced weight loss may exist

Liraglutide for treating type 1 diabetes

<p><b>Introduction</b>: Many persons with type 1 diabetes do not achieve glycemic targets, why new treatments, complementary to insulin, are of interest. Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist could be a potential pharmacological supplement to insulin. This review discusses the mechanism of actions, efficacy and safety of liraglutide as add-on to insulin in persons with type 1 diabetes.</p> <p><b>Areas covered</b>: Physiological and clinical data on liraglutide in type 1 diabetes were reviewed. We searched the Cochrane library, MEDLINE and EMBASE, with the final search performed February 16, 2016.</p> <p><b>Expert opinion</b>: Liraglutide as adjunct to insulin treatment reduced body weight and daily dose of insulin compared with insulin alone. The effect on HbA1c was inconsistent with mostly uncontrolled, small-scale studies reporting improvements in glycemic control. In placebo-controlled studies there was no clinically relevant effect on HbA1c. Adverse events were mostly transient gastrointestinal side effects, primarily nausea. Based on the available data, liraglutide cannot be recommended as add-on therapy to insulin in persons with type 1 diabetes with the aim to improve glycemic control. Ongoing trials in newly diagnosed patients with type 1 diabetes and in insulin pump-treated patients will help define the future role of liraglutide therapy in type 1 diabetes.</p