MD Conference Express EASD 2012 - (Page 16)
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c l i n i c A l
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H i g H l i g H T s
Mean ± standard deviation (SD) baseline characteristics were similar in the linagliptin versus placebo groups: age, 59.7±9.9 versus 60.4±10.0 years; BMI, 30.8±5.4 versus 31.2±4.9 kg/m2; HbA1C, 8.3%±0.9% in both groups; and basal insulin dose, 41.5±31.9 versus 40.1±27.3 IU/day. Mean exposure to study medication was comparable in both groups: 435 days for linagliptin versus 422 days for placebo. Overall safety and tolerability of linagliptin was similar to placebo. The proportion of patients with ≥1 adverse event (AE) was slightly lower with linagliptin (78.4%) compared with placebo (81.4%); most AEs were of mild or moderate intensity. Despite better glycemic control with linagliptin, the incidence of hypoglycemia was similar in both groups (linagliptin 31.4%; placebo 32.9%), and the number of severe hypoglycemic events was low (linagliptin 1.7%; placebo 1.1%; Table 1). Mean ± SD change in body weight was minimal and comparable between the treatment groups (linagliptin –0.30±3.70 kg; placebo –0.04±3.10 kg). Table 1. Incidence of Hypoglycemia in Linagliptin and Placebo Groups.
Week 24
Linagliptin 5 mg QD Placebo
This trial demonstrated that linagliptin as add-on therapy to basal insulin significantly improved glycemic control after 24 weeks and did so independently of renal function and type of basal insulin. It was not associated with an increased risk of hypoglycemia or weight gain. Adding a DPP-4 inhibitor instead of a sulfonylurea to further improve glucose control might avoid hypoglycemia and weight gain.
12-Week Treatment with LY2409021 Significantly Lowers HbA1C and Is Well Tolerated in Patients with Type 2 Diabetes Mellitus
Written by Maria Vinall
End of Treatment
Linagliptin 5 mg QD Placebo
The glucagon receptor antagonist LY2409021 (LY) substantially lowers HbA1C without severe hypoglycemia or weight gain in type 2 diabetes mellitus (T2DM) patients. In a double-blind, randomized, placebo-controlled, Phase 2 study presented by Christof M. Kazda, MD, Eli Lilly and Company, Suresnes, France, researchers examined the margin between LY efficacy and safety by comparing mean changes in HbA1C and liver aminotransferases at 3 dose levels. T2DM pathophysiology is characterized by greater postprandial glucose release, impaired insulin secretion, and abnormal glucagon plasma levels [Woerle HJ et al. Am J Physiol Endocrinol Metab 2006]. LY is a potent, selective glucagon receptor antagonist that inhibits hepatic glucose output and has significant glucose-lowering effects [Kelly RP et al. ADA 2011 Abstract 1004-P; Tham LS et al. ADA 2011 Abstract 416-PP]. In a Phase 1 study [NCT01606397], LY improved glycemic parameters and showed reversible dose-dependent increases in serum aminotransferase levels. The incidence of hypoglycemia was infrequent and was considered to be of mild to moderate intensity [Kelly RP et al. ADA 2011 Abstract 305-OR]. The primary endpoint of the current Phase 2a study [NCT00871572] was mean change in HbA1C and liver aminotransferases. Secondary objectives included the evaluation of LY effects on blood glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and blood lipids, as well as safety and tolerability. Patients aged 18 to 70 years with T2DM (HbA1C 6.5% to 10%) and a body mass index of 25 to 40 kg/m2 who were
Number of patientsa Hypoglycema (%)
Any confirmed symptomatic
1 hypoglycemia with plasma
631 22.0
630 23.2
631 31.4
630 32.9
17.0
18.7
23.9
25.1
glucose ≤3.9 mmol/L (70 mg/dL) Any confirmed symptomatic
2 hypoglycemia with plasma
8.6
8.7
14.3
14.1
glucose ≤3 mmol/L (54 mg/dL) Any severe hypoglycemic episode
3
0.3
0.6
1.7
1.1
a Treated set: all patients who were treated with at least one dose of the study medication. 1 Accompanied by typical symptoms of hypoglycemia. 2 Accompanied by typical symptoms of hypoglycemia, but no need for external assistance. 3 Requiring the assistance of another person to actively administer carbohydrate, glucagon, or other actions.
The placebo-adjusted mean ± standard error (SE) change in HbA1C from baseline to Week 52 was –0.53%±0.05% (p<0.0001). This was accompanied by a mean ± SE change in basal insulin dose up to Week 52 of +2.6±0.8 IU/day for linagliptin versus +4.2±0.8 IU/day for placebo (p<0.003).
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November 2012
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Table of Contents for the Digital Edition of MD Conference Express EASD 2012
MD Conference Express EASD 2012
Contents
Understanding Incretin Hormone Action and the Treatment of Diabetes
New ADA/EASD Guidelines Focus on Patient-Centered Care
ORIGIN Trial: Insulin Glargine and n-3 Fatty Acids Fail to Reduce CV Events in Diabetic Patients
Exenatide Once Weekly Sustained Improvement in Glycemic Control with Weight Loss Through 4 Years
DiaPep277® Shows Promise as a Therapeutic Strategy for T1DM
Linagliptin Proves Safe and Effective as Add-on Therapy to Basal Insulin
12-Week Treatment with LY2409021 Significantly Lowers HbA1C and Is Well Tolerated in Patients with T2DM
Insulin Degludec Is Superior to Sitagliptin in Improving Glycemic Control in Uncontrolled Patients with Type 2 Diabetes on Oral Agents
Dapagliflozin Does Not Impact Renal Function in Patients with T2DM
Population-Based Screening for T2DM:The ADDITION-Cambridge Trial
The Challenges of Pharmaceutical Management of Painful Diabetic Peripheral Neuropathy
Enterovirus Infection
Novel Oral Agents
GLP-1
Genetics
Renal Denervation
Hypertension and Renal Function Are Risk Factors for CAD in T1DM
MD Conference Express EASD 2012
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