Liraglutide as initial pharmacological therapy for type 2 diabetes mellitus

New treatments for type 2 diabetes mellitus are needed to retain insulin—glucose coupling and lower the risk of weight gain and hypoglycemia.

What is Liraglutide?

Liraglutide, which if approved, will be marketed under the brand-name "Victoza", is a long-acting glucagon-like peptide-1 (GLP-1) analog that is being developed by Novo Nordisk for the treatment of type 2 diabetes. Liraglutide has a half-life after subcutaneous injection of 11–15 hours, making it suitable for once-daily dosing (in contrast to Byetta's twice daily).


Liraglutide. Image source: Wikipedia, public domain.


Figure 1. Action of DPP-4 inhibitors. Note that DPP-4 normally inactivates GLP-1. DPP-4 inhibitors block DPP-4 which in turn leaves GLP-1 active.
Click to enlarge the figure. Created with Gliffy.

What is Glucagon-like peptide-1 (GLP-1)?

Glucagon-like peptide-1 (GLP-1) is a GI peptide that stimulates insulin secretion (similar to sulfonylureas). GLP-1 also inhibits glucagon release, gastric emptying and food absorption. GLP-1 and another similar peptide are called incretins. As noted above, incretins have a dual action which leads to lowering blood glucose:

1. Stimulate insulin release

2. Inhibit glucagon release

Exenatide (Byetta) is a GLP-1 receptor agonist approved for adjunctive therapy for patients with DM 2 who are not well controlled on oral agents. It is available only as injections and has to be administered twice daily.

DPP-4 inhibitors or gliptins

Two new medications increase GLP-1 levels by blocking the enzyme which inactivates GLP-1. The enzyme is called DPP-4 (dipeptidyl peptidase-4) and the new medications are called DPP-4 inhibitors or gliptins.

They act similarly to Byetta (see figure above) but have the big advantage to be available in oral form (pills). These 2 new medications for treatment of DM2 are:

- Sitagliptin (Januvia) is taken once a day and it costs about $ 4.50 per pill

- Vildagliptin (Galvus) is waiting for FDA approval but it is already speculated to be at a competitive disadvantage to Januvia because it has to be taken twice a day

New Liraglutide Study

In a double-blind, double-dummy, active-control, parallel-group study, 746 patients with early type 2 diabetes were randomly assigned to once daily liraglutide or glimepiride 8 mg for 1 year.

HbA1c decreased by 0·51% with glimepiride, compared with 0·84% with liraglutide 1·2 mg and 1·14% with liraglutide 1·8 mg. Six patients in the liraglutide groups discontinued treatment because of vomiting.

The authors conclude that liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and leads to greater reductions in HbA1c, weight, hypoglycaemia, and blood pressure than does glimepiride.

References:
Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. The Lancet, Volume 373, Issue 9662, Pages 473 - 481, 7 February 2009.
Liraglutide, from Wikipedia, the free encyclopedia.
DPP-4 Inhibitors for Treatment of Diabetes

2 comments:

  1. No clinical endpoints tested (stroke, infarction, renal failure...).
    A study of <400 patients for one year doesn not give enough enformation on drug safety esp. rare events.

    ReplyDelete
  2. Martin,

    I don't think the study focused on reduction of stroke, infarction, renal failure - in any case, a duration of 52 weeks would be too short to assess for those. Usually, it takes 5-10 years to assess for those complications prospectively.

    Regarding your second point - 400 patients is a large study. Most of the rare events you mentioned show in post-market analysis.

    I hope this helps.

    ReplyDelete

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