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Getting Past the Sticker Shock of Drugs

R. Keith Campbell, RPh, CDE and Danial Baker, PharmD

Even though drug companies spend close to a billion dollars to bring a newproduct to market and maintain an exclusive right to it for less than 10years, on average, the general impression among consumers is that medicationsare overpriced rip-offs. Yet outpatient drug costs account for only 10 centsof each health caredollar.¹ Many peoplewho need medications do not acknowledge that buying a drug can help one feelbetter, stay out of the hospital, get cured, prevent complications, be able towork, and perhaps even save money over the long run.

Diabetes treatment options have grown more than threefold since 1995, fromtwo to seven classes of drugs that make it possible to nearly normalize bloodglucose. But our health care system—which is acutecare–oriented—is reluctant to spend a little more to treat thepatient, instead paying enormous amounts of money for hospitalization forcoronary bypass surgeries, kidney transplants, and amputations.

Let's hope that patients will be able to use some of the following new,more precise products being developed to normalize blood glucose, lipids,inflammatory factors, and blood pressure. This should reduce the risk ofcardiovascular death and chronic diabetes complications. Even if theshort-term costs of care increase, long-term costs could be reducedsubstantially.

RECENT DEVELOPMENTS

Within the past 2 years, two drugs have been approved for treating painfulperipheral neuropathy—duloxetine (Cymbalta, Lilly) and pregabalin(Lyrica, Pfizer) (DOC News, March 2005). Incretins, a completely newclass of medications—including exenatide (Byetta, Amylin/Lilly), thefirst to be approved by the Food and Drug Administration (FDA)—recentlybecame available to help type 2 patients lose weight, reduce glycatedhemoglobin (A1C) levels, and improve postprandial blood glucose levels(DOC News, July 2005). The Guardian RT, a continuous blood glucosemonitor, is available now from Medtronic MiniMed, and others will be availablesoon—the FreeStyle Navigator from Abbott and DexCom (DOC News,March 2006). In addition, the FDA approved pulmonary insulin early this year(Exubera, Pfizer) (DOC News, March 2006), and new easier-to-useinsulin pumps are indevelopment.

ON THE HORIZON

Following are some of the promising new drugs being evaluated by the FDAthat, if approved, could provide additional hope to patients and their healthcare providers.

• Rimonabant (Acomplia, Sanofi-Aventis) offers great potential to helppatients lose weight and has been shown to reduce insulin resistance andassist patients to stop smoking (DOC News, September 2005). It is acannabinoid receptor–blocker, and an FDA advisory panel has recommendedits approval as a weight-loss agent.
  
• Mecasermin (Increlex, Tercica) is a replacement therapy for treatinginsulin-like growth factor-1 deficiency and is in phase II trials to treatpatients with type 2 diabetes associated with severe insulin resistance. It isinjected twice a day and has been shown to reduce insulin requirements inthese patients by56%.²
  

Pulmonary Insulins

• Exubera received FDA approval last winter (DOC News, March 2006).Several other inhaled insulins are in clinical trials.
  
• Technosphere, developed by Mannkind Corp., is delivered by a smallproprietary device called the MedTone inhaler. It has a rapid onset and shortduration that facilitates as much as 50% absorption of the insulin in thelungs.³
  
• Alkermes is working with Eli Lilly to bring to market a small device thatadministers pulmonary insulin.
  

Oral Insulin
• Oral-lyn, manufactured by Generex, is sprayed into the mouth with adevice called a RapidMist. The insulin is absorbed by the buccal mucosa. It isapproved in Ecuador.

Oral Incretins
Several companies are in late stages of developing a new class of drugcalled dipeptidyl peptidase-IV (DPP-IV) inhibitors to help maintain theactivity of glucagon-like peptide-1 and produce effects on blood glucosesimilar to those of exenatide. Drugs include:

• Sitagliptin (Januvia, Merck)—Merck expects FDA action on its new drugapplication by this fall.
  
• Vildagliptin (Galvus, Novartis)—Novartis has submitted a new drugapplication.
  

COMPLICATION-FIGHTING COMPOUNDS

Following are new drugs being designed to combat the cripplingcomplications of diabetes. None is yet approved specifically for diabetestreatment.

• Ruboxistaurin (Arxxant, Lilly) is an exciting drug in phase III clinicaltrials. It is an inhibitor of protein kinase C-beta, allowing it to block oneof the pathways by which sustained excess glucose causes microvascularcomplications. If approved, it will be used to prevent or treat retinopathyand possibly nephropathy and neuropathy.
  
• Benfotiamine, available from some micronutrient companies, is a derivativeof thiamine, or vitamin B-1. It has been shown to be a transketolase activatorthat blocks the hexosamine pathway, which is involved in the development ofmicrovascularcomplications.⁴
  
• Copper-zinc superoxide dismutase is a catalytic antioxidant that alsointerrupts one of the pathways that causes microvascularcomplications.⁴
  
• Botulinum toxin A (Botox, Allergan), when administered with a 200 Uintrapylorin injection, has helped several patients with severe diabeticgastroparesis.⁵Gastric emptying time and other symptoms were significantly improved.
  
• Hyaluronidase (Vitrase, ISTA) slows the progression of diabetic retinopathyand can liquefy existing blood clots when injected into the vitreoushumor.⁶
  
• Pegaptanib (Macugen, Pfizer) inhibits vascular endothelial growth factorwhen injected into the vitreous humor. If approved, it will be used to treatdiabetic macular edema and diabeticretinopathy.⁷
  
• The O₂Misly system developed by IYIA Technologies has shownpromising results in treating diabetic foot ulcers. It uses hyperbaric oxygenand an antimicrobial mist to cut ulcer healing time inhalf.⁸
  
• Ertapenem sodium (Invanz, Merck) is a once-daily injectable antibiotic fortreating moderate to severely complicated foot infections in diabetes patientswithout osteomyelitis.
  
• Lamotrigine (Lamictal, GlaxoSmithKline) is an anticonvulsant agent in phaseIII studies to determine its utility in treating patients with painfuldiabetic neuropathies.
  

PREVENTION PIPELINE

Aaron I. Vinik, MD, PhD, of the Strelitz Diabetes Institutes at EasternVirginia Medical School in Norfolk, spearheaded the discovery of the geneINGAP, a protein responsible for regenerating islet cells. An isolated INGAPpeptide can help control the production of insulin. In animal models it hasbeen shown to produce new beta-cells faster than existing beta-cells aredestroyed.⁹

Many agents and technologies are being researched and clinically tested toimprove outcomes for diabetes patients and reduce cardiovascular risk, butwill we be able to afford these new products? And will they help us deliversubstantially better care?

Footnotes

R. Keith Campbell, RPh, CDE, and Danial Baker, PharmD, are professors ofpharmacotherapy at Washington State University College of Pharmacy in Pullmanand Spokane, respectively.

Note of disclosure: Dr. Campbell has been a speaker for Eli Lilly,Sanofi-Aventis, and Novo Nordisk.

References

1. California HealthCare Foundation: Snapshot: Health care costs 101,2006. Available online atwww.chcf.org/documents/insurance/HealthCareCosts06.pdf.Accessed April 12, 2006.

2. Mohamed-Ali V, Pinkney J: Therapeutic potential of insulin-likegrowth factor-1 in patients with diabetes mellitus. TreatEndocrinol 1:399–410, 2002.

3. Pfutzner A, Forst T: Pulmonary insulin delivery by means of theTechnosphere drug carrier mechanism. Expert Opin DrugDeliv 2:1097–1106, 2005.

4. Brownlee M: The pathobiology of diabetic complications: A unifyingmechanism. Diabetes 54:1615–1625, 2005.[Free Full Text]

5. Lacy BE, Crowell MD, Schettler-Duncan A, et al.: The treatment ofdiabetic gastroparesis with botulinum toxin injection of the pylorus.Diabetes Care 27:2341–2347, 2004.[Abstract/Free Full Text]

6. Hyaluronidase (Vitrase)—ISTA: Hyaluronidase—ISTApharmaceuticals. Drugs R D 4:194–197, 2003.[Medline]

7. Adamis AP, Altaweel M, Bressler NM, et al.: Changes in retinalneovascularization after pegaptanib (Macugen) therapy in diabetic individuals.Ophthalmology 113:23–28, 2006.[Medline]

8. Wolf CJ, Wilson L: O₂Misly wound treatment system whenadded to the standard of care in non-healing foot ulcers. Available online athttp://www.iyiatechnologies.com/Misly.htm.Accessed March 31, 2006.

9. Rosenberg L, Lipsett M, Yoon JW, et al.: A pentadecapeptidefragment of islet neogenesis-associated protein increases beta-cell mass andreverses diabetes in C57BL/6J mice. Ann Surg 240: 875–884, 2004.[Medline]

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This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Campbell, R. K. Articles by Baker, D. Search for Related Content PubMed Articles by Campbell, R. K. Articles by Baker, D. Social Bookmarking                What's this?