PHOENIX – Patients with type 1 diabetes who received high doses of once-daily insulin degludec had fewer episodes of nocturnal hypoglycemia compared with those who received a similar dose of insulin glargine, a meta-analysis of two randomized trials has shown.
"The issue is of particular concern in patients with high BMIs," said Dr. Helena Rodbard, who presented the unpublished study at the annual meeting of the American Association of Clinical Endocrinologists.
Dr. Helena W. Rodbard
Insulin degludec is a new basal insulin with an ultralong and stable glucose-lowering effect. A previous prospective meta-analysis of phase IIIa trials comparing insulin degludec with insulin glargine showed that patients with type 1 diabetes who were on degludec had a statistically significant, 17% lower rate of nocturnal hypoglycemia across the entire treatment period and a 25% lower rate during the maintenance period (16 weeks onward), compared with those who took glargine (Diabetes Obes. Metab. 2013;15:175-84).
In their post-hoc meta-analysis, Dr. Rodbard and her colleagues compared the hypoglycemia rates for a subset of type 1 diabetes patients who required high doses of either degludec or glargine in two published trials (Lancet 2012;379:1489-97; J. Clin. Endocrinol. Metab. 2013;98:1154-62).
Nearly 25% of the patients – 235 out of a total of 950 patients in the two trials – received an end-of-trial basal insulin dose of more than 0.45 U/kg and were included in the meta-analysis.
The results showed that compared with glargine, degludec was associated with significantly lower rates of nocturnal confirmed hypoglycemia, by 36% in the full trial period (risk ratio [RR], 0.64) and by 44% in the maintenance period (RR, 0.56).
"Since patients taking higher doses of basal insulin have a longer duration of action than that seen in patients taking small doses of basal insulin, it is apparent that duration of action does not explain the benefit observed with insulin degludec," said Dr. Alan J. Garber, professor of medicine, biochemistry and molecular biology, and molecular and cellular biology at Baylor College of Medicine, Houston, and the immediate past president of the AACE. "Instead, the other dose-related characteristic of basal insulin, namely the [maximum serum concentration] of insulin, seems to explain this finding. Thus, if one basal insulin has a greater peak effect than another, it will have a greater hypoglycemic potential at higher as compared to lower doses. That is what we saw here and therefore explains the finding, owing most likely to the more definable peak of glargine compared to degludec." Dr. Garber was not involved in the study.
Dr. Alan J. Garber
Meanwhile, the mean end-of-trial basal insulin dose was similar for degludec (0.63 U/kg) and glargine (0.65 U/kg). Patients also had similar mean end-of-trial hemoglobin A1c values with degludec and glargine, at 7.41% and 7.55%, respectively.
The mean end-of-trial fasting plasma glucose levels were comparable between degludec (133 mg/dL) and glargine (136 mg/dL), at 133 mg/dL and 136 mg/dL. Also, rates of overall confirmed hypoglycemia (plasma glucose less than 56 mg/dL) did not differ significantly between the two insulins in either the full trial period or the maintenance period.
"These findings are consistent with results for the overall study population, confirming that [insulin degludec] is a well tolerated and effective basal insulin choice for patients with [type 1 diabetes] across the spectrum of insulin requirements," said Dr. Rodbard.
Dr. Rodbard is an adviser and speaker for, and has receiving research support from, several companies including AstraZeneca, Blondel, Eli Lily, Merck, Novo Nordisk, and Sanofi. Dr. Garber is a consultant/advisory board member, and/or is on the speakers bureaus, for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.
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