DPP-4 Inhibitors for Treatment of Diabetes

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


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. The diagram Action of DPP-4 inhibitors is now on Wikipedia.

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.

Two new medications increase GLP-1 levels by blocking the enzyme which inactivates GLP-1. The enzymes 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

References:
New Medications
Merck Wins U.S. Approval for a New Diabetes Drug. NYTimes.
Sitagliptin: First DPP-4 Inhibitor for Type 2 Diabetes. Resident and Staff Physician, 04/2007.
Merck Diabetes Drug Could Face Competition from Takeda. WSJ Health Blog, 01/2008.

Related:
Lilly, Amylin Disclose More Cases of Byetta-Related Pancreatitis. WSJ Health Blog, 08/2008.
FDA Issues Warning for Diabetes Drug Byetta about possible kidney problems, including renal failure http://bit.ly/1UOjwB

Updated: 11/03/2009

6 comments:

  1. $4.50 a pill to produce, and probably $14.50 a pill to sell.

    ReplyDelete
  2. Studies with Vildagliptin as well as sitagliptin were conducted both twicw a day and once a day. Sitagliptin received approval for a once a day indication having the same type of studies as vildagliptin, even though there are quite fewer vildagliptin studies out there. So what leads you to believe that vildagliptin will be twice a day and not once a day like sitagliptin? Are you aware that sitagliptin has a dosage warning with renal impared patients??? Your answer would be very interesting!

    ReplyDelete
  3. ***CORRECTION*** THERE ARE QUITE FEWER SITAGLIPTIN STUDIES OUT THERE VS/. VILDAGLIPTIN. VILDAGLIPTIN HAS MORE STUDIES TO BACK UP IT'S EFFICACY, SAFETY & TOLERABILITY!!!! SORRY FOR THE TYPO.

    ReplyDelete
  4. Beajerry,

    According to Merck, Januvia cost is about $ 4.50 a pill to sell, not to produce.


    Anonymous,

    According to NYTimes (see reference above):

    "Januvia may have an edge because it clearly works as a once-a-day pill, while Galvus was initially formulated to be taken twice daily. Novartis, the manufacturer of Galvus, now claims that its drug is effective when taken once daily, but doctors may be skeptical of that claim."

    Januvia dose is 100 mg po qd; in patients with renal impairment, the dose is 50 mg po qd.

    ReplyDelete
  5. The glucagon bandwagon is rolling ... Whatever happened to the insulin resistance bandwagon?

    ReplyDelete
  6. Let's not rush to jump to the bandwagon....remember wat happened to rosiglitazon? Have we not learnt ur lessons?

    ReplyDelete

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