Lyxumia: once-daily injection for type II diabetes

Lyxumia (lixisenatide) is a once-daily parenteral hypoglycaemic for the management of uncontrolled type II diabetes in combination with oral hypoglycaemics and/or insulin.

Lyxumia (lixisenatide) should be injected subcutaneously into the thigh, abdomen or upper arm once daily within 60 minutes before breakfast or the evening meal
Lyxumia (lixisenatide) should be injected subcutaneously into the thigh, abdomen or upper arm once daily within 60 minutes before breakfast or the evening meal

PHARMACOLOGY

Lixisenatide is a selective glucagon-like peptide-1 (GLP-1) receptor agonist, which stimulates glucose-dependent insulin secretion from pancreatic beta cells.1

Lixisenatide also suppresses glucagon secretion and slows gastric emptying, reducing the rate at which meal-derived glucose appears in the circulation.1

CLINICAL STUDIES

Study programme

The safety and efficacy of once-daily subcutaneous lixisenatide in type II diabetes were evaluated in the GetGoal clinical trial programme (n=3,825), comprising 6 randomised double-blind, placebo-controlled studies, and 1 randomised open-label study using exenatide as an active control.1

Eligible patients had been diagnosed with type II diabetes at least 1 year before the screening visit and had an HbA1c of 7-10% (except in GetGoal-Duo 1, see below). The primary endpoint in all studies was mean change in HbA1c at week 24.1-8

Vs oral hypoglycaemics

Lixisenatide was investigated in combination with metformin (GetGoal-F1 and GetGoal-M), a sulfonylurea (GetGoal-S), pioglitazone (GetGoal-P) or a combination of these agents. Treatment with lixisenatide resulted in significant reductions in HbA1c, fasting plasma glucose and 2-hour post-prandial glucose after a test meal in all studies at week 24, compared with placebo. The HbA1c reduction was significant whether lixisenatide was administered in the morning or the evening.1-5 

Vs twice-daily exenatide

In GetGoal X (n=634), once-daily lixisenatide resulted in an HbA1c reduction of -0.79% at week 24 compared with -0.96% for twice-daily exenatide, with a mean treatment difference of 0.17% (95% CI, 0.033-0.297). This met the pre-specified non-inferiority margin (0.4%). A similar percentage of patients in the lixisenatide and exenatide groups achieved an HbA1c below 7%: 48.5% and 49.8%, respectively.6 

The incidence of symptomatic hypoglycaemia up to week 24 was significantly lower with lixisenatide than exenatide (2.5% vs 7.9%, p<0.05), as was the incidence of nausea (24.5% vs 35.1%, p<0.05).6

In combination with insulin

GetGoal-L (n=496) evaluated the efficacy of lixisenatide as add-on therapy to basal insulin, with or without metformin. Patients were randomised to receive lixisenatide 20 microgram daily (starting at 10 microgram daily for one week then 15 microgram for one week) or placebo. At week 24, lixisenatide was associated with significantly greater reductions than placebo in HbA1c (-0.74% vs -0.38%, p<0.001) and body weight (-1.8kg vs -0.5kg, p<0.0001).7

In the GetGoal-Duo 1 study (n=446), lixisenatide was studied as add-on therapy to insulin glargine with metformin, with or without a glitazone. Patients completed an initial 12-week run-in phase where morning administration of insulin glargine was started at 10 units and then titrated on a weekly basis to achieve a fasting glycaemic target of 4.4-5.6mmol/mol. Patients who achieved an HbA1c of 7-9% were then randomised to lixisenatide (titrated as in GetGoal-L) or placebo. At week 24, lixisenatide had reduced HbA1c  to a greater extent than placebo: -0.7% vs 0.4% (p<0.0001).8

Safety profile

The most frequently reported adverse reactions in studies were nausea, vomiting and diarrhoea, which were usually mild and transient.

Hypoglycaemia was reported very commonly when lixisenatide was used in combination with a sulfonylurea or basal insulin, and commonly when given in combination with metformin. Prescribers should consider reducing the dose of sulfonylurea or insulin when prescribing lixisenatide.1

Lixisenatide decreases the rate of gastric emptying, which may reduce the rate of absorption of orally administered drugs. Prescribers should use lixisenatide with caution in patients receiving drugs that require rapid gastrointestinal absorption or have a narrow therapeutic index.1

References:

  1. Lyxumia Summary of Product Characteristics, February 2013.
  2. Ahren B et al. Diabetes Care 2013 Mar 27 [Epub ahead of print].
  3. Bolli GB et al. Poster presented at 47th EASD Annual Meeting. Lisbon, Portugal. September 2011.
  4. Ratner RE et al. Poster presented at 47th EASD Annual Meeting. Lisbon, Portugal. September 2011.
  5. Pinget M et al. Poster presented at 72nd American Diabetes Association Annual Conference. Philadelphia, PA. June 2012. 
  6. Rosenstock J et al. Poster presented at 47th EASD Annual Meeting. Lisbon, Portugal. September 2011.
  7. Aronson R et al. Poster presented at 72nd American Diabetes Association Annual Conference. Philadelphia, PA. June 2012.
  8. Riddle MC et al. Diabetes Care 2013, accepted article; DOI: 10.2337/dc12-2462.

View Lyxumia drug record

Further information: Sanofi

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