Liraglutide

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Analogue of GLP-1 effective in type 2 diabetes with superior properties to glimepiride[1][2] and superior glycaemic control to sitagliptin[3]. More importantly it has potential in managing obesity as short term therapy up to 20 weeks is associated with better weight loss than orlistat and the drug profile is consistent with a favourable effect on pre-diabetes and hypertension[4]. Long term studies are awaited (there is a possible risk of endocrine malignancy) and in this indication it has important clinical potential[5].

Contents

Indications

  • Type 2 diabetes mellitus in combination therapy starting at 0.6 mg/day subcutaneously and titrating slowly to 1.8 mg/day. However as of 2010 there is little if any evidence of increased benefit over 1.2mg/day.
  • Obesity

Place in therapy

A comparative study against exenatide found it had better and more predictable glycaemic control. Although it was better tolerated in terms of side effects, there was a trend towards hospital admission events not obviously associated with therapy being more than with exenatide [6][7]. Its place in therapy is likely to be dictated by marketing decisions of respective manufacturers with health economic considerations being presently hard to evaluate as the data is from relatively short term followup. The use in obesity has shown good tolerability at up to 3mg/day and proportional dose related clinical effectiveness.

Contra-indications

Cautions

Do not give iv or im.

Side-effects

Adverse event frequency at 4% is very comparable to other treatments[7].

Interactions

  • Sulphonylurea dose may need reduction to prevent hypoglycaemia

Pharmacology

  • Half life about 13 hours
  • 97% structural homolog to human GLP-1
  • Produced by recombinant DNA technology in Saccharomyces cerevisiae culture

References

  1. Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2008 Sep 24.(Epub ahead of print) (Link to article – subscription may be required.)
  2. Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, Düring M, Matthews DR. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes care. 2009 Jan; 32(1):84-90.(Link to article – subscription may be required.)
  3. Blonde L, Montanya E. Comparison of liraglutide versus other incretin-related anti-hyperglycaemic agents. Diabetes, obesity & metabolism. 2012 Apr; 14 Suppl 2:20-32.(Link to article – subscription may be required.)
  4. Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009 Oct 22.(Epub ahead of print) (Link to article – subscription may be required.)
  5. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. The New England journal of medicine. 2015 Jul 2; 373(1):11-22.(Link to article – subscription may be required.)
  6. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009 Jul 4; 374(9683):39-47.(Link to article – subscription may be required.)
  7. a b Buse JB, Falahati A. Adverse events in diabetes drug trial — Authors' reply. Lancet 2009;374(9696):1144-45
  8. Jensen TM, Saha K, Steinberg WM. Is There a Link Between Liraglutide and Pancreatitis? A Post Hoc Review of Pooled and Patient-Level Data From Completed Liraglutide Type 2 Diabetes Clinical Trials Diabetes Care published ahead of print December 12, 2014, doi:10.2337/dc13-1210