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Liraglutide improves insulin secretion in long-standing, poorly controlled type 2 diabetes
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Adults with long-standing type 2 diabetes requiring high-dose insulin therapy saw improved insulin secretion and reduced liver and subcutaneous fat when randomly assigned liraglutide for 6 months, study findings show.
“We found that adding liraglutide to high-dose insulin therapy in [patients with obesity] with longstanding and uncontrolled type 2 diabetes improves glycemia primarily through improvement in insulin secretion and not through suppression of glucagon secretion,” Anna Vanderheiden, MD, a research fellow at the University of Texas Southwestern Medical Center in Dallas, and colleagues wrote. “Furthermore, we did not observe significant changes in insulin sensitivity in this cohort despite significant reductions in [subcutaneous adipose tissue] and liver fat content.”
Researchers analyzed data from 71 adults with long-standing type 2 diabetes (mean of 17 years) requiring high-dose insulin therapy (> 1.5 units/kg per day; mean 2.2 units/kg daily). Researchers randomly assigned participants to received 1.8 mg liraglutide daily (n = 35) or matching placebo (n = 36) for 6 months and then measured changes in insulin and glucagon secretion using a 4-hour, mixed meal challenge. Participants underwent MRI to estimate subcutaneous and visceral fat in the abdomen and ectopic fat in the liver and pancreas. All background medications remained stable during the study period.
Participants in the liraglutide group saw significantly improved HbA1c over 6 months vs. those assigned placebo, with a between-group difference of –0.9% (95% CI, –1.5 to –0.4), as well as a greater reduction in BMI (P = .01) and weight (P = .02).
Researchers found a significant improvement in insulin secretion in the liraglutide group following the meal challenge, as measured by area under the curve (AUC) of C-peptide (P = .002) and the AUC ratio of C-peptide to glucose (P = .003).
There were no significant between-group differences in insulin sensitivity as measured by the Matsuda Index; glucagon secretion also did not change significantly between groups.
Liver fat and subcutaneous fat decreased in the liraglutide group vs. placebo (P = .0006 and P = .01, respectively); however, there were no significant between-group differences for visceral and pancreatic fat. – by Regina Schaffer
Disclosure: The study was supported by an investigator-initiated trial grant from Novo Nordisk. One study author reports receiving consulting and research grants from Astra Zeneca, GI Dynamics, Janssen, Novo Nordisk and Pfizer/Merck; another study author is employed by Phillips Medical Systems.
“Adding liraglutide to high-dose insulin therapy ... improves glycemia primarily through improvement in insulin secretion and not through suppression of glucagon secretion.”
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