Hypoglycemia Risk Related to Double Dose Is Markedly Reduced with Basal Insulin Peglispro Versus Insulin Glargine in Patients with Type 2 Diabetes Mellitus in a Randomized Trial: IMAGINE 8.
BACKGROUND
Basal insulin peglispro (BIL) has a peripheral-to-hepatic distribution of action that resembles endogenous insulin and a prolonged duration of action with a flat pharmacokinetic/pharmacodynamic profile at steady state, characteristics that tend to reduce hypoglycemia risk compared to insulin glargine (GL). The primary objective was to demonstrate that clinically significant hypoglycemia (blood glucose ≤54 mg/dL [3.0 mmol/L] or symptoms of severe hypoglycemia) occurred less frequently within 84 h after a double dose (DD) of BIL than a DD of GL.


METHODS
This was a randomized, double-blind, two-period crossover study in patients with type 2 diabetes (T2D) previously treated with insulin (N = 68). For the first 3 weeks of each of the two crossover periods, patients received an individualized dose of BIL or GL once nightly (stable dose for 2 weeks/period). Then, during a 7-day inpatient stay with frequent blood glucose monitoring and standardized meals, one DD of study insulin was given. Glucose was infused if blood glucose was ≤54 mg/dL (3.0 mmol/L) or for symptoms of severe hypoglycemia.


RESULTS
Within 84 h after the DD, a significantly smaller proportion of patients experienced clinically significant hypoglycemia with BIL compared to GL (BIL, 6.6%; GL, 35.5%; odds ratio for BIL/GL 0.13 [95% confidence interval 0.04-0.39]; P < 0.001). Adverse event profiles were similar for the two insulins. Serum alanine aminotransferase and triglyceride levels were significantly higher with BIL versus GL.


CONCLUSIONS
BIL has a markedly lower risk of hypoglycemia than GL when replicating a double-dose error in patients with T2D.
['Harris|Cynthia|C|', 'Forst|Thomas|T|', 'Heise|Tim|T|', 'Plum-Mörschel|Leona|L|', 'Watkins|Elaine|E|', 'Zhang|Qianyi|Q|', 'Fan|Ludi|L|', 'Garhyan|Parag|P|', 'Porksen|Niels|N|']
D000293:Adolescent D000328:Adult D000368:Aged D001786:Blood Glucose D018592:Cross-Over Studies D003924:Diabetes Mellitus, Type 2 D004305:Dose-Response Relationship, Drug D004311:Double-Blind Method D005260:Female D006801:Humans D007003:Hypoglycemia D007004:Hypoglycemic Agents D000069036:Insulin Glargine D061268:Insulin Lispro D008297:Male D008875:Middle Aged D011092:Polyethylene Glycols D012306:Risk D016896:Treatment Outcome D055815:Young Adult
Hypoglycemia Type 2 diabetes Basal insulin peglispro (BIL) Fasting blood glucose Insulin therapy.