New Drugs for Diabetes Treatment

Category: Diabetes by Jonah-Lynne Padigus, PharmD - January 21, 2014 | Views: 16526 | Likes: 3 | Comment: 0

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New diabetes drugs

Diabetes Mellitus Facts and Statistics

Diabetes is a health condition in which the body is unable to properly use glucose (sugar) for energy resulting in high levels of blood glucose (hyperglycemia). There are two types of diabetes. In Type 1 diabetes, the pancreas can no longer produce insulin and thus glucose is unable to enter the cells for use as energy. In Type 2 diabetes, either the pancreas does not produce an adequate amount of insulin or the body cannot respond properly to insulin. Type 2 diabetes is the most common form. Individuals with hyperglycemia usually experience signs and symptoms of frequent urination (polyuria), excessive thirst (polydipsia), and excessive hunger (polyphagia).

  • 25.8 million children and adults in the United States, 8.3% of the population, have diabetes.
  • 7.0 million Americans have undiagnosed diabetes.
  • 1.9 million Americans aged 20 years or older are diagnosed with diabetes every year (5,205/day).
  • 26.9% of the elderly (aged 65 or older) have diabetes.
  • 15,600 individuals younger than 20 years are diagnosed with type 1 diabetes and 3,600 are diagnosed with type 2 diabetes each year.
  • The U.S. economic cost of diagnosed diabetes is $245 billion annually.
  • Heart disease death rates and the risk of stroke are 2 to 4 times greater among adults with diabetes.
  • Diabetes kills more Americans each year compared to breast cancer and AIDS combined.

Newest Medications for Treatment of Type 2 Diabetes

Dipeptidyl Peptidase 4 (DPP-4) Inhibitors

Although DPP-4 inhibitors have been available for almost 8 years they are newer than sulfonylureas and metformin. The first DPP-4 inhibitor, sitagliptin (Januvia), was FDA approved in 2006 for use with diet and exercise and was later approved in 2007 for its use in combination with metformin or thiazolidinediones. The second DPP-4 inhibitor, saxagliptin (Onglyza), was approved in 2009 for monotherapy and in combination with metformin, sulfonylurea, or thiazolidinediones. The next DPP-4 inhibitor, linagliptin (Tradjenta), was approved in 2011 for both monotherapy and combination therapy with metformin, sulfonylureas, or pioglitazone. The latest DPP-4 inhibitor, alogliptin (Nesina), was FDA approved in 2013 as monotherapy or in combination with metformin, sulfonylureas, thiazolidinediones, and insulin.

DPP-4 inhibitors increase the amount of two proteins (incretin hormones) found in the body, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Incretin hormones tell the body to release insulin and lower blood glucose. GLP-1 also decreases the production of glucose and slows down the absorption of glucose.

Incretin hormones are removed from the body by an enzyme called dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors block this enzyme resulting in GLP-1 and GIP to stay in the body longer and therefore decrease blood glucose levels.

Efficacy of DPP-4 Inhibitors

  • The effectiveness of DPP-4 inhibitors used as monotherapy or in combination with other oral antidiabetic drugs is shown in multiple clinical trials lasting from 12-52 weeks.
    • Average decrease in HbA1c from baseline ranges between 0.5 to 1.9%
    • Average decrease in fasting plasma glucose (FPG) from baseline is 9 to 46 mg/dL
  • A head-to-head trial of saxagliptin 5 mg or sitagliptin 100 mg with metformin therapy demonstrated non-inferiority (one drug was not inferior to the other).

Side Effects of DPP-4 inhibitors

  • Upper respiratory tract infection and common cold symptoms (runny nose, sore throat, or nasal congestion)
  • Headache
  • Pancreatitis (inflammation of the pancreas)
  • Abdominal pain, nausea, diarrhea (sitagliptin)
  • Urinary tract infection (saxagliptin)
  • Hypoglycemia (low levels of blood glucose; more common with alogliptin)

Additional Facts

  • DPP-4 inhibitors are taken orally with or without food and have once a day dosing.
  • They are safer than sulfonylureas when comparing the rate of hypoglycemic episodes.
  • They do not affect weight.
  • In patients with impaired renal function, linagliptin is the only DPP-4 inhibitor that does not require a dose adjustment.

List of DPP-4 Inhibitors and their Average Wholesale Price (AWP) per Pill 

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Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists

The first GLP-1 receptor agonist, exenatide (Byetta) was FDA approved in 2005. The latest GLP-1 receptor agonist, liraglutide (Victoza), was approved in 2010. The extended-release formulation of exenatide, Bydureon, was FDA approved in 2012. All three medications are used as monotherapy with diet and exercise or in combination with metformin, sulfonylureas, or thiazolidinediones.

GLP-1 receptor agonists activate the GLP-1 receptor which leads to insulin production and release when blood glucose levels are high. They also stop the liver from making too much glucose, reduce appetite, and slow down how much food and glucose leave the stomach and get absorbed into the blood, preventing hyperglycemia after meals.
 

Also Read: Bydureon Versus Victoza Efficacy, Safety, Weight Loss 
 

Efficacy of GLP-1 Agonists

  • Clinical trial results have shown that exenatide combined with other oral antidiabetic drugs effectively reduces HbA1c by 0.4 to 1.5% in patients with type 2 diabetes inadequately controlled on metformin with or without a sulfonylurea.
  • The Liraglutide Effect and Action in Diabetes (LEAD) trials have shown that liraglutide effectively improves blood glucose control (up to a 1.5% decrease in HbA1c) in individuals with type 2 diabetes, when used as monotherapy or in combination with other oral antidiabetic drugs.
  • A head-to-head 26-week trial of once-daily liraglutide compared with twice-daily exenatide showed that liraglutide significantly reduced HbA1c by 21.12% compared to 20.79% with exenatide.
  • A head-to-head 26-week trial of once weekly Bydureon versus once daily liraglutide indicated that liraglutide provided a greater change in HbA1c (-1.48% compared to -1.28% with Bydureon).

Side Effects of GLP-1 Receptor Agonists

  • Gastrointestinal symptoms (nausea, vomiting, constipation, diarrhea)
  • Kidney failure and pancreatitis (exenatide)
  • Thyroid tumors (liraglutide)

Additional Facts

  • Exenatide is injected under the skin twice a day or once weekly (Bydureon) within 60 minutes prior to meals.
  • Liraglutide is injected under the skin once daily at any time of the day.
  • When GLP-1 receptor agonists are used in combination with a sulfonylurea, the risk of hypoglycemia increases.
  • Clinical trial data for GLP-1 receptor agonists have shown a weight loss of 2.3 to 2.8 kg when used as monotherapy and a range of 2.6 to 2.9 kg when used in combination with metformin.
  • Clinical results have demonstrated liraglutide’s potential as a weight loss drug for non-diabetic, obese patients.
    • After 1 year, liraglutide subjects lost 5.8 kg compared to 3.8 kg in the placebo group. The liraglutide group maintained a 2-year weight loss of 7.8 kg. 

List of GLP-1 Agonists and their Average Wholesale Price (AWP)

Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors

The first SGLT2 inhibitor, canagliflozin (Invokana), was FDA approved in 2013 and the second drug in this class, dapagliflozin (Farxiga), was approved in 2014. Both medications are used as monotherapy with diet and exercise or in combination with metformin and sulfonylureas.

SGLT2 inhibitors decrease blood sugar by blocking the kidney from reabsorbing it and removing excess sugar through the urine. They do this by blocking the sodium-glucose co-transporter-2 (SGLT2) in the kidney that is responsible for reabsorbing sugar back into the body.

Efficacy of SGLT2 Inhibitors

  • The effectiveness of SGLT2 inhibitors used as monotherapy or in combination with other oral antidiabetic drugs is shown in multiple clinical trials lasting from 26-52 weeks.
    • Average decrease in HbA1c levels from baseline by 0.70 to 2.10%
    • Average decrease in fasting plasma glucose (FPG) from baseline by 21.2 to 61.0 mg/dL

Side Effects of SGLT2 Inhibitors

  • Fungal infections especially in women
  • Urinary tract infections
  • Common cold symptoms such as runny nose, sore throat, or nasal congestion
  • Increased urination
  • Hyperkalemia (high levels of potassium, more common with canagliflozin)
  • Bladder cancer (dapagliflozin)

Additional Facts

  • Canagliflozin is taken orally once daily before the first meal of the day. 
  • Dapagliflozin is taken orally once daily in the morning, with or without food.
  • Dapagliflozin has no known drug interactions.
  • Clinical trial data for SGLT2 inhibitors have shown a weight reduction range of 2.2 to 3.9 kg when used as monotherapy and a range of 2.6 to 4.2 kg when used in combination with metformin.

List and Average Wholesale Price (AWP) of SGLT2 Inhibitors

Conclusion

Metformin remains the cornerstone of most type 2 diabetes treatment regimens. Many patients may require combination therapy in order to achieve glycemic goals. These latest drug classes are beneficial in patients not receiving adequate blood glucose control from other drug classes. They also offer additional benefits such as better tolerability, weight loss, and a greater efficacy when combined with other antidiabetic medications such as metformin. Although some drugs in these classes may be expensive, the price should be weighed against the benefit in decreasing the burden of the disease.

References

American Diabetes Association Data and Statistics about Diabetes

Astrup et al. (2012). Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. International Journal of Obesity. 36: 843-854.

Dicker, D. (2011). DPP-4 inhibitors. Diabetes Care. 34(2): 276-278.

Farxiga Prescribing Information (Package Insert, Label)

Garber, A.J. (2011). Long-acting glucagon-like peptide 1 receptor agonists. Diabetes Care. 34(2): 279-284.

Invokana Prescribing Information (Package Insert, Label)

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The material on this site is for information only and is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider.
 

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