Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo‐controlled trial

Abstract

AimTo confirm the superiority, compared with placebo, of adding liraglutide to pre‐existing basal insulin analogue ± metformin in adults with inadequately controlled type 2 diabetes [glycated haemoglobin (HbA1c) 7.0–10.0% (53–86 mmol/mol)].MethodsIn this 26‐week, double‐blind, parallel‐group study, conducted in clinics or hospitals, 451 subjects were randomized 1 : 1 to once‐daily liraglutide 1.8 mg (dose escalated from 0.6 and 1.2 mg/day, respectively, for 1 week each; n = 226) or placebo (n = 225) added to their pre‐existing basal insulin analogue (≥20 U/day) ± metformin (≥1500 mg/day). After randomization, insulin adjustments above the pre‐study dose were not allowed. The primary endpoint was HbA1c change.ResultsAfter 26 weeks, HbA1c decreased more with liraglutide [−1.3% (−14.2 mmol/mol)] than with placebo [−0.1% (−1.2 mmol/mol); p < 0.0001]. More subjects on liraglutide reached HbA1c targets: <7.0% (59% vs 14%; p < 0.0001) and ≤6.5% (43% vs 4%; p < 0.0001) using slightly less insulin (35.8 IU vs 40.1 IU). Greater decreases from baseline (estimated treatment differences vs placebo; p < 0.0001) occurred in fasting plasma glucose (−1.3 mmol/l), seven‐point glucose profiles (−1.6 mmol/l), body weight (−3.1 kg) and systolic blood pressure (−5.0 mmHg). Transient gastrointestinal adverse events (nausea: 22.2% vs 3.1%) and minor hypoglycaemia (18.2% vs 12.4%) were more frequent with liraglutide than placebo, and pulse increased (4.5 beats/min) compared with placebo. No severe hypoglycaemia or pancreatitis occurred.ConclusionsAdding liraglutide to a basal insulin analogue ± metformin significantly improved glycaemic control, body weight and systolic blood pressure compared with placebo. Typical gastrointestinal symptoms and minor hypoglycaemia were more frequent with liraglutide.

Beneficial Effects of Incretin-Based Therapy on Glycemic Control, Adipokines, Insulin Sensitivity Parameters and Weight Loss in Overweight or Obese Patients With Newly Diagnosed Type 2 Diabetes: A Prospective Study

“…Our study supports previous data on liraglutide improvements in glucose control and weight reduction. HbA1c improvement was directly related to basal HbA1c in concordance with previous studies [9][10][11]. As indicated in our study, greater proportion of patients treated with liraglutide reached the target level of HbA1c < 7% than the other two agents, without accompanying an increased risk of hypoglycemia.…”

“…Many studies indicated that both GLP-1RA and DPP4i have the priority over metformin and sulfonylurea in reducing plasma glucose and body weight, and increasing insulin sensitivity. However, these studies seldom select the newly diagnosed diabetic patients as subjects, and rarely evaluate the adipokines profile [8][9][10][11]. To our knowledge, no studies have addressed the effect of liraglutide and sitagliptin treatment on plasma glycemic control, weight loss and circulating adipokines in newly diagnosed diabetic patients in daily clinical practice.…”

Effects of Combination Therapy with Liraglutide and Insulin Glargine as the Initial Treatment for Hyperglycemic Patients with Type 2 Diabetes: An Observational Study

“…It has already been reported that better glucose-lowering effects can be obtained by additional administration of liraglutide in patients with type 2 diabetes on insulin therapy without developing hypoglycemia or weight gain, and that insulin requirements can be reduced [6][7][8][9][10]. It is very interesting that simultaneous and combined use of liraglutide and insulin glargine as the initial treatment in patients with type 2 diabetes under hyperglycemic or so-called glucotoxic conditions resulted in similar effects to those reported previously.…”

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

“…The rate of confirmed hypoglycaemia was significantly ( P < 0.0001) lower with liraglutide than with insulin aspart, while gastrointestinal AEs occurred more frequently with liraglutide. Another 26‐week study that compared liraglutide with placebo, both added to basal insulin with or without metformin, found that both HbA 1c and body weight decreased significantly ( P < 0.0001) more with liraglutide than with placebo 42. Gastrointestinal AEs were more common with liraglutide relative to placebo, as was confirmed hypoglycaemia ( P = 0.04).…”