San Diego, CA—Insulin degludec, an investigational ultra-long-acting insulin, achieved comparable lowering of plasma glucose compared with long-acting insulin glargine, according to 2 phase 3, 52-week, “treat-to-target” clinical trials: one in type 2 diabetes and one in type 1 diabetes. In the study of type 2 diabetes, less hypoglycemia and nocturnal hypoglycemia were observed with degludec; in the study of type 1 diabetes, overall hypoglycemia was the same in both arms, but the incidence of nocturnal hypoglycemia was reduced by insulin degludec to a similar extent as in the type 2 diabetes trial.
“The finding of less hypoglycemia and less nocturnal hypoglycemia was not a fluke result. It showed up in a meta-analysis of 7 phase 3 registration trials for degludec, with a consistent favoring for degludec versus glargine of a 25% relative risk reduction in nocturnal hypoglycemia,” said Alan Garber, MD, PhD, Professor, Baylor College of Medicine, Houston, TX, who presented results of the type 2 diabetes trial at the 2011 Scientific Sessions of the American Diabetes Association. “These studies suggest that insulin degludec potentially offers substantial benefits for patients and the management of their diabetes.”
Type 2 Diabetes Trial
The researchers randomized 1006 patients with type 2 diabetes previously treated with insulin and oral drugs in a 3:1 ratio to either insulin degludec plus insulin aspart (IAsp) plus or minus metformin plus or minus pioglitazone versus insulin glargine and IAsp plus or minus metformin plus or minus pioglitazone. Insulin degludec was given with the evening meal, whereas insulin glargine was given any time of day, but at a consistent time of day for each patient. Treatment was for 52 weeks, and about 83% of patients completed 1 year of treatment.
The trial was designed as a noninferiority comparison of insulin degludec versus insulin glargine, and met its primary end point. Similar control of plasma glucose was achieved in both arms, and no difference between arms was observed for total, daily, and basal-bolus dose of insulin. Severe and confirmed minor hypoglycemia were grouped together. An 18% relative risk reduction in hypoglycemia was observed with insulin degludec versus insulin glargine (11.6 vs 13.6 episodes per patient-year, respectively; P = .036), and the difference between arms was evident at 12 weeks. Insulin degludec reduced the incidence of nocturnal hypoglycemia by 25% (4.4 vs 5.9 episodes per patient-year, respectively; P = .040) versus insulin glargine. The difference in nocturnal hypoglycemia was apparent at 1 month and continued throughout the trial.
“More than 80% of patients had 1 or more episodes of confirmed hypoglycemia; nocturnal hypoglycemia was less common, around 40%,” Dr Garber said.
Quality of life favored insulin degludec, and adverse events were similar in the 2 arms.
Type 1 Diabetes Trial
In this trial, 516 patients with type 1 diabetes were randomized to either insulin degludec (at alternating morning and evening doses) plus IAsp versus insulin glargine (given any time of day but at the same time for each patient) plus IAsp in a 3:1 ratio: 472 patients for insulin degludec and 154 for insulin glargine.
Hemoglobin (Hb)A1c was reduced by approximately 0.4% in both arms, to a final HbA1c of 7.3%, meeting the noninferiority end point. Both arms had similar rates of overall confirmed hypoglycemia; however, those receiving insulin degludec had a 25% relative risk reduction of nocturnal confirmed hypoglycemia versus insulin glargine (P = .021). The mean total daily doses of insulin at 1 year were 9% higher for the insulin glargine group, with a 50:50 split of basal-bolus doses of both groups.
In both trials, weight gain was similar in both treatment arms. In the type 2 trial, many patients were receiving pioglitazone, which is known to increase weight.
In both the type 1 and type 2 diabetes trials, the most common adverse events occurring in more than 5% of patients were influenza, nasopharyngitis, upper respiratory tract infection, arthralgia, back pain, pain in extremity, headaches, diarrhea, peripheral edema, wrong drug administered, cough, and hypertension; these events were similarly distributed in both treatment arms.