In type 2 diabetes treated with high-dose insulin, liraglutide reduced HbA1c

For type 2 diabetes patients taking at least 1.5 U/kg of insulin per day, adding liraglutide reduced HbA1c and weight compared to placebo, according to a recent study. The randomized controlled trial of 71 patients found that mean HbA1c decreased from 9.0% to 7.9% in the liraglutide group while remaining unchanged at 8.9% in the placebo group. The hypoglycemia rate was higher in the first month after initiation of liraglutide, but the overall hypoglycemia rate over the 6-month follow-up was similar between groups.

The study was published in the July JAMA Internal Medicine. The following commentary by Krista Gonzales, MD, ACP Member, and Gunjan Y. Gandhi, MD, MSc, was published in the ACP Journal Club section of the Oct. 18 Annals of Internal Medicine.

Patients with diabetes receiving intensive insulin therapy with various combinations of basal and prandial insulin can be caught in a vicious but common cycle, whereby insulin requirements increase over time, and this in turn contributes to weight gain and hypoglycemia and further increases in insulin dosing. At this stage, clinicians observe a practical limit to the efficacy of insulin titration alone on glucose-lowering and often add or continue metformin to reduce insulin resistance; use concentrated insulin, such as U-500 insulin; or consider weight loss surgery if patients meet criteria.

Injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide, are a relatively new addition to our treatment armamentarium. These drugs improve postmeal glucose control and insulin sensitivity and contribute to weight loss. Treatment with basal insulin plus GLP-1 RAs is well-established in diabetes guidelines and may be as effective as adding prandial insulin therapy. When GLP-1 RAs are started, a preemptive reduction in insulin dosage by 25% to 30% in patients with HbA1c <9% may reduce the risk for hypoglycemia.

The trial by Vanderheiden and colleagues supports previous findings of reduced insulin requirements and improved glucose control and weight loss in patients who required high doses of insulin and received liraglutide. Weight loss, although modest for some patients, is an important outcome and may increase patient satisfaction.

GLP-1 RAs should not be used in patients with a history of pancreatitis, gastroparesis, personal or family history of medullary thyroid cancer, or multiple endocrine neoplasia type 2. Gastrointestinal side effects, additional burden of injections, risk for hypoglycemia, and high cost may be barriers to use.

The US Food and Drug Administration may soon approve combination basal insulin with a GLP-1 RA, and this may simplify therapy for patients with severe insulin resistance. Future research should assess the effects of GLP-1 RAs combined with multiple daily insulin regimens over longer periods to determine cardiovascular safety and if they improve patient-important outcomes.