PHOENIX – Patients who had higher rates of confirmed hypoglycemia also had greater daily variations in fasting blood glucose, regardless of diabetes type or insulin drug, according to a meta-analysis of seven trials on two long-acting basal insulin drugs.
"The data clearly show that the variation in plasma glucose is associated with hypoglycemia," said Dr. Bruce W. Bode, who presented the study at the annual meeting of the American Association of Clinical Endocrinologists.
Previous studies have shown that patients whose fasting blood glucose changes daily, due to pharmacokinetics and pharmacodynamics of basal insulin, have a difficult time adjusting their insulin dose. This, in turn, can put them at an increased risk of a hypoglycemic event. "We also need to look at what patients do and what they eat. We should look at what causes hypoglycemia in them," said Dr. Bode, a diabetes specialist at Atlanta Diabetes Associates.
The study analyzed data from seven open-label, randomized, treat-to-target published phase IIIa trials, which had compared once-daily insulin degludec (Novo Nordisk) and insulin glargine (Sanofi-Aventis).
Two trials included individuals with type 1 diabetes and five trials included those with type 2 diabetes. The trials had a 26- or 52-week duration. Daily within-subject variability (coefficient variance [CV%]) in self-measured prebreakfast plasma glucose was determined from three consecutive daily measurements made in the final week of each trial. The analysis did not compare degludec with glargine.
The CV% was compared between individuals with the highest rate of confirmed hypoglycemic events (top 25%) and those outside of this range (bottom 75%), using a linear mixed model.
Results showed that, in individuals with type 1 diabetes, the CV% ratio (top 25%/bottom 75%) was 1.33 for degludec and 1.25 for glargine, Dr. Bode said.
In insulin-experienced patients with type 2 diabetes receiving basal insulin plus oral antidiabetic therapy, the ratio was 1.33 for degludec and 1.46 for glargine, he said.
For insulin-naive patients with type 2 diabetes in whom basal insulin plus oral antidiabetic therapy was initiated in the trials, the ratios were 1.33 for degludec and 1.49 for glargine. Patients with type 2 diabetes on basal-bolus therapy had identical ratios of 1.65.
In the pooled data from type 2 diabetes trials, the ratio was 1.50 for degludec and 1.46 for glargine.
With both insulins, estimated day-to-day variability in prebreakfast plasma glucose was significantly higher for patients with the highest rates of confirmed hypoglycemia than for those with lower rates, regardless of diabetes type, type 2 diabetes treatment history, or insulin type (P less than .05), Dr. Bode reported.
Dr. Alan Garber, the outgoing AACE president and session moderator, said that "it will be interesting to go back and analyze the data to see what patient characteristics, irrespective of the type of insulin, predict great risk of variability."
Dr. Bode has been a speaker, consultant, and advisory board member for, and has received research funding from several companies, including Novo Nordisk, SanofiAventis, Eli Lily, and Medtronic. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.
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