Liraglutide’s Effect on HbA1c in Type 1 Diabetes

Addition of the glucagon-like peptide (GLP)-1 receptor agonist liraglutide to insulin therapy did not have any significant effect on HbA1c levels in a group of patients with poorly controlled type 1 diabetes, according to the results of a study published recently in Diabetes Care. However, the drug did significantly reduce body weight and insulin requirements, researchers found.

“The current study was inspired by previous clinical and physiological studies suggesting that GLP-1 and GLP-1 receptor agonists decrease postprandial glucose and glucagon levels, slow the gastric emptying rate, and decrease meal-related insulin requirements in patients with type 1 diabetes, regardless of residual b-cell function,” wrote researcher Christian S. Frandsen, from the Department of Endocrinology, Hvidovre Hospital, University of Copenhagen. “Contrary to our hypothesis, the present results indicate that concomitant treatment with liraglutide 1.2 mg once daily and insulin does not improve HbA1c levels during 12 weeks of follow-up more than insulin treatment alone.”

The randomized, placebo controlled, double-blind study including 40 patients who were randomly assigned to 12 weeks of treatment with once-daily liraglutide 1.2 mg or placebo in addition to their usual insulin regimens. All patients in the study were aged 18 to 70, had a BMI between 18 and 28, HbA1c of 8% or greater, and no residual beta-cell function.

The study’s primary endpoint was change in HbA1c. Both groups of patients had baseline HbA1c levels of about 9%. No significant difference in HbA1c occurred from baseline to week 12 between the liraglutide and placebo groups (-0.6 vs. -0.5; P=0.62).

The researchers did observe significant changes in body weight for those patients assigned liraglutide. Patients assigned the drug had a mean change in body weight of -3.13 kg compared with +1.12 kg for placebo (P<0.0001).

“Importantly, our patients were normal weight, and even patients with lower starting BMIs lost weight, suggesting that this mechanism to some extent is independent of the starting weight,” the researchers wrote. “This implies that caution should be paid to the patient’s baseline weight if initiation of GLP-1 treatment is considered.”

The mean bolus insulin dose also decreased in patients assigned liraglutide compared with placebo (4.0 IU vs. 0.0 IU; P=0.02).

The study showed that liraglutide was associated with a significant increase in heart rate (P=0.04) and more frequent gastrointestinal adverse effects. In addition, patients assigned liraglutide had a placebo-adjusted decrease in mean systolic blood pressure of about 3 mmHg.

“The clinical significance of these cardiovascular effects is unknown; consequently, it is currently an area of active research in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER), Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL; ClinicalTrials.gov Identifier: NCT01144338), Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA; ClinicalTrials.gov Identifier: NCT01147250), and Researching Cardiovascular Events With a Weekly Incretin in Diabetes trials,” the researchers wrote.

No difference in hypoglycemia was observed between the two study groups.

Reference: Frandsen CS, et al. Twelve-week treatment with liraglutide as add-on to insulin in normal-weight patients with poorly controlled type 1 diabetes: a randomized, placebo-controlled, double-blinded parallel study. Diabetes Care. 2015 Oct 20 [Epub ahead of print].