MedWire News: Moderate doses of liraglutide combined with glimepiride provide better glycemic control along with a more favorable weight profile than rosiglitazone plus glimepiride or placebo, report investigators from the LEAD (Liraglutide Effect and Action in Diabetes) 3 study.
“Most drugs that target Type 2 diabetes also cause weight gain or hypoglycemia, or both, with the risk increasing with combination therapy,” explain Michel Marre (Groupe Hospitalier Bichat–Claude Bernard, Paris, France) and team.
However, glucagon-like peptide-1 (GLP-1)-based therapies such as liraglutide “stimulate insulin secretion and reduce glucagon secretion only during hyperglycemia.” GLP-1 also acts to reduce appetite and slow gastric emptying, they add.
In this study, 1041 adults with Type 2 diabetes, aged 56 years on average, were randomly assigned to take glimepiride 2–4 mg/day plus liraglutide 0.6, 1.2, or 1.8 mg/day, rosiglitazone 4 mg/day, or placebo for a period of 26 weeks.
Liraglutide 1.2 and 1.8 mg/day, rosiglitazone, and liraglutide 0.6 mg/day reduced patients’ glycated hemoglobin (HbA1c) levels by 1.1%, 0.4%, and 0.6%, respectively, compared with baseline, whereas a 0.2% increase in HbA1c was seen in the placebo group.
In a similar fashion, fasting plasma glucose decreased by 1.6 mmol/l and 1.0 mmol/l in the liraglutide 1.2 and 1.8 mg/day and rosiglitazone groups, respectively, and corresponding postprandial plasma glucose by 2.6 mmol/l versus 1.8 mmol/l. Fasting plasma glucose increased by 0.9 mmol/l and postprandial plasma glucose decreased by 0.4 mmol/l in the placebo group.
Of note, treatment with liraglutide 0.6 mg/day produced similar or lower reductions in plasma glucose than rosiglitazone.
Regarding body weight, individuals in the liraglutide 1.8 mg/day and placebo groups lost 0.2 and 0.1 kg, respectively, over the study period, whereas those in the liraglutide 1.2 mg/day group gained 0.3 kg and those in the rosiglitazone group gained 2.1 kg.
Adverse events were similar across all five study groups and were generally low at 3–5%. The most common side effects were gastrointestinal.
Marre et al conclude: “Liraglutide is an effective and well-tolerated once-daily human GLP-1 analogue that improves overall glycemic control and indices of pancreatic βcell function with minimal weight gain and risk of hypoglycemia when used in combination with a sulfonylurea for Type 2 diabetes.”
The results are published in the journal Diabetic Medicine.
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