• Diabetes Mellitus
• Hyperglycemia/Hypoglycemia
• Diabetes & Endocrinology Clinical Trials

• Diabetes Mellitus
• Endocrinology
• Diabetes & Metabolic Syndrome
• Hyperglycemia/Hypoglycemia
• Diabetes & Endocrinology Clinical Trials

A fixed-ratio combination of insulin degludec and liraglutide significantly improves glycemic control in patients with type 2 diabetes mellitus (T2DM) compared with either drug as monotherapy, with a low risk of hypoglycemia. Data from a Phase 3 randomized, 3-arm, open-label study were discussed by Stephen C. L. Gough, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.

The fixed-ratio combination is delivered in a once-daily single-injection device, consisting of insulin degludec 1 U and liraglutide 0.036 mg. It was compared with its individual components, liraglutide or insulin degludec alone, in a 26-week study of insulin-naïve patients with T2DM (n=1663) who were inadequately controlled on metformin plus/minus pioglitazone. Patients were randomized to the fixed-dose combination insulin degludec/liraglutide once daily (n=834), insulin degludec (n=414), or liraglutide 1.8 mg (n=415). The dosages of the fixed-dose combination and insulin degludec were titrated to achieve a mean fasting plasma glucose (FPG) of 72 to 90 mg/dL.

The primary endpoint was the change in HbA1C level over 26 weeks. HbA1C decreased by a mean of 1.91% (from 8.3% to 6.4%) in the patients randomized to fixed-dose insulin degludec/liraglutide, which was superior to liraglutide (1.28% reduction in HbA1C) and noninferior to insulin degludec (1.44% reduction in HbA1C).

Some 80.6% of patients treated with the fixed-dose combination reached the HbA1C goal of <7%, and 69.7% reached <6.5%, compared with 60.4% and 41.4%, respectively, with liraglutide alone, and 65.1% and 47.5%, respectively, with insulin degludec alone.

The fixed-dose insulin degludec/liraglutide combination also resulted in a mean weight reduction of 0.5 kg compared with a 2.2-kg increase with insulin degludec alone. The rate of confirmed hypoglycemia was 32% lower with fixed-dose insulin degludec/liraglutide than with insulin degludec. As expected, liraglutide was associated with less hypoglycemia and greater weight reduction than either basal insulin formulation.

At 26 weeks, change in FPG was similar for fixed-dose insulin degludec/liraglutide (5.6 mmol/L) and insulin degludec (5.8 mmol/L), compared with 7.3 mmol/L with liraglutide (p<0.0001 vs fixed-dose insulin degludec/liraglutide). An identical reduction in FPG level from baseline (65 mg/dL) in each insulin group occurred even though the final mean daily dose of insulin degludec in the group randomized to the fixed-dose combination was 15 U/day lower than in the group randomized to insulin degludec alone, said Prof. Gough.

Nine-point glucose profiles showed significantly lower mean prandial increments with fixed-dose insulin degludec/liraglutide and liraglutide compared with insulin degludec following all three main meals.

Gastrointestinal side effects with fixed-dose insulin degludec/liraglutide occurred less frequently than with liraglutide.

Fixed-dose insulin degludec/liraglutide combines the effects of insulin degludec and liraglutide in one injection, resulting in a substantial overall improvement in glycemic control with a low risk of hypoglycemia and weight gain, concluded Prof. Gough.

• © 2013 MD Conference Express®