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New options for diabetes.

Diabetes is a chronic progressive disease that, if not tightly controlled, can progress to significant morbidity and mortality. As a result, it is necessary to treat diabetes early and effectively in order to halt or slow the progression as much as possible.

There are several things to take into consideration when treating diabetes: efficacy, cost, effect on weight and patient preference. Also important is awareness of the complications associated with each medication and the percentage reduction in hemoglobin Ale needed. Several new products with unique mechanisms of action are now available. In combination with diet and exercise, these products may be the key to lowering the patient's Ale to goal. In particular, two new classes of medications--sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists--have shown promising results.

Sodium-glucose cotransporter 2 inhibitors (SGLT2) work by blocking the sodium-glucose cotransporter 2, which is responsible for reabsorbing the glucose filtered by the kidney. These agents are also thought to have a small effect on SGLT1, one of the transporters responsible for absorption of intestinal glucose. If the glucose is not reabsorbed, it will be eliminated; therefore, the reduction of absorbed glucose will result in a lower rise in post prandial glucose and insulin release. A bonus effect is that SGLT2s regulate glucose with indifference to insulin production and excretion. SGLT2 inhibitors are oral medications indicated for treating type 2 diabetes. But studies are examining these medications for possible use in treating type I diabetes as well.

Though this medication class is generally considered well tolerated, some adverse reactions should be noted. During clinical trials, genital mycotic and urinary tract infections were common and more likely in females. Patients should receive regular blood work to observe for changes in renal function and electrolyte status. These medications should be discontinued if the threshold for eGFR has been reached. Volume depletion also is possible, and patients (especially if taking a diuretic) should be counseled on its symptoms, such as orthostatic hypotension, syncope and dehydration.

Volume reduction is one of the postulated mechanisms of blood pressure reduction, whereas weight loss is associated with a reduction in body fat mass. If the patient is currently taking an insulin secretagogue or insulin when an SGLT2 is added, consider lowering the dose of the insulin secretagogue or insulin to avoid hypoglycemia. Doses can be increased as needed once the SGLT2 is on board.

The Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial is a landmark trial that showed superiority in cardiovascular outcomes with an SGLT2. More trials are in progress.

Glucagon-like peptide-1 receptor agonists bind and activate the GLP-1 receptor, which increases glucose-dependent insulin secretion from pancreatic beta cells. These products are regulated by elevated blood glucose levels and "turn off" when then the glucose levels begin to fall. This class of medication also regulates glucagon secretion. All but one of these products have a structural modification to prevent the degradation by dipeptidyl peptidase-4, which prolongs their half-life, resulting in mostly once daily or weekly administration. GLP-1 receptor agonists are indicated for the treatment of type 2 diabetes, but there are ongoing clinical trials for use in type 1 diabetes. Though this class is also considered to be generally well tolerated, some adverse reactions warrant counseling.

Before patients start these products, ask them about any family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, both of which are contraindications for use. There have been postmarketing reports of acute pancreatitis. Counsel patients on signs and symptoms of pancreatitis, such as severe abdominal pain which may radiate to the back (possibly with vomiting), and to seek medical care immediately if such symptoms occur.

Regular lab work is indicated at baseline and throughout the course of therapy in order to rule out renal or liver impairment or failure, possible thyroid carcinoma and electrolyte changes due to dehydration. Cautious use of these products with medications that may alter the patient's glycemic state (e.g., sulfonylureas, insulin) or hydration status (e.g., non-steroidal anti-inflammatory drugs, ACE inhibitors).

Immunogenicity occurred during clinical trials, which did not necessarily affect glycemic control in every patient but may be why certain patients are not obtaining their glycemic target. An increase in heart rate and/or atrial fibrillation or flutter also occurred, and an increase in international normalized ratio (INR) may occur with exenatide.

Different types of insulin were not studied with each of the GLP-1 receptor agonists, so the use of various insulin products cannot be recommended. Injection sites should be rotated, and insulin (if used) should be injected in a different area.

Positive side effects include weight loss and decreased appetite, possibly due to increased satiety. Encourage the reading of the patient information and understanding of the handling, preparation, storage and injection of the various products.

These products offer a promising alternative mechanism of action for diabetes treatment and may be considered as an add-on therapy or if secondary failure occurs with other products. The long-term safety of these products and any reduction in diabetes-related complications, remains to be determined.

Tara Muzyk, Pharm. D., is a clinical pharmacy writer based in Lebanon, Pa. She has extensive experience as a clinical pharmacist and has served as an associate professor of pharmacy at the University of Southern Nevada College of Pharmacy and as education director for the VA Southern Nevada Healthcare System.
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Title Annotation:Focus
Author:Muzyk, Tara
Publication:Chain Drug Review
Date:Mar 14, 2016
Words:889
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