A new drug to lower blood glucose and treat type 2 diabetes

Tradjenta™Last Monday, May 2, the FDA approved a new medication for type 2 diabetes. It’s pretty safe to argue that this is a common co-morbidity among patients in rehabilitation. And as far as medications that are important in physical therapy go, those that can change blood glucose (either raising or lowering it) are probably medications that physical therapists and other rehabilitation professionals should understand. The new drug, an inhibitor of dipeptidyl peptidase-4 (DPP-4), is linagliptin (Tradjenta™). It joins 2 other DPP-4 inhibitors available in the US, sitagliptin (Januvia™) and saxagliptin (Onglyza™) among a large number of treatment options for people with type 2 diabetes.

What is DPP-4 and why inhibit it, you might ask? This is an enzyme that breaks down incretin hormones, chemicals produced within the gastrointestinal tract in response to an ingested, carbohydrate-containing meal. There are several hormones that belong to this group, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). The most important action of these hormones, especially GLP-1, is to stimulate insulin release by the pancreas. The drug does this in a glucose-dependent manner, meaning that hypoglycemia is relatively uncommon. GLP-1 only stimulates the pancreas to produce insulin to the degree that glucose levels increase – more glucose, more stimulation of insulin secretion and vice versa. Other effects of the incretins include the suppression of glucagon secretion, gastric emptying, and appetite, and maybe even the stimulation of beta cell proliferation in the pancreas.1 The beta cells, remember, are responsible for producing insulin, so this is a good thing if it is happening. By inhibiting the action of the enzyme that breaks these incretin hormones down, there are more molecules of the hormones available for a longer period of time, increasing their effects. The bottom line is that these drugs lower blood glucose, whether you are looking at finger sticks or A1C. Linagliptin, like the other DPP-4 inhibitors, can be taken alone or in combination with other oral diabetes medications. It has not been studied in combination with insulin.2

In rehabilitation, the DPP-4 inhibitors do not create any major issues, and linagliptin seems to fall in line with the other members of the drug class. The most common adverse effects might be important to the patient, but don’t really factor into rehabilitation management – these include a stuffy or runny nose, or a sore throat. In rehabilitation, the major concern with drugs that are capable of lowering blood glucose is hypoglycemia. Because of the way these drugs work, there is not a significant risk of hypoglycemia associated  with linagliptin or any of the other DPP-4 inhibitors. The risk increases when a patient is also taking a sulfonylurea, but therapists should already be wary of hypoglycemia in individuals taking sulfonylureas. Pancreatitis has been noted to occur more often in patients being treated with linagliptin (as well as sitagliptin) than in those taking a placebo, but the absolute risk is very small. Any patient with signs or symptoms of acute pancreatitis – new onset of abdominal discomfort and tenderness, nausea and vomiting – should warrant the concern of the treating therapist, whether or not a medication is implicated in producing the problem.

These drugs have only been “in the wild” since October of 2006, when sitagliptin was approved by the FDA, so it remains to be seen what other concerns might arise with long-term use of these agents. DPP-4 is expressed in many other tissues in the body, and the long-term effects of inhibiting its action are unknown.3

Now you have one less question to ask when you see patients coming in to your clinics taking yet another drug you’ve never heard of. And remember, just because it’s new doesn’t mean it’s better than drugs that are already out there.

Back to text
1. Langley AK, Suffoletta TJ, Jennings HR. Dipeptidyl peptidase IV inhibitors and the incretin system in type 2 diabetes mellitus. Pharmacotherapy. 2007;27:1163-1180.
2. Boehringer Ingelheim Pharmaceuticals. Tradjenta™ prescribing information. Available at http://www.tradjenta.com. Accessed May 12, 2011.
3. Sitagliptin/metformin (Janumet) for type 2 diabetes. Med Lett Drugs Ther. 2007;49:45-47.

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These are 10 you should know

What medications are most commonly taken by patients in your practice? If you can’t name 5 of them, you might want to compile some data and figure out what’s in your top 10. Then, make sure clinicians in your practice are familiar with these drugs and the issues associated with their use. If you’d like a shortcut, the IMS Institute for Health Care informatics has published a document entitled The Use of Medicines in the United States: Review of 2010, available here for your perusal. IMS is a privately held, international pharmaceutical marketing research firm that was established in 1954 and is headquartered in Norwalk, CT. There are a couple of interesting facts to be found in their report, along with several Top 10 lists, one of which is the focus here.

Guess how many prescriptions were filled at retail pharmacies in 2010? A million? A billion? Try 3.99 billion. This is up 1.2% from 2009, and from 3.2 billion in 2001. Interestingly, the per capita volume is relatively unchanged in that time, so while there are more people who are filling prescriptions, there aren’t more prescriptions per person being filled. For accounting purposes, a prescription is a prescription, whether it is for a 30 day supply of a medication or a 90 day supply. So, the Top 10 Drugs of 2010 were:

10. hydrochlorothiazide (Hydrodiuril®, and an ingredient in Dyazide®, Zestoretic®, Lotensin HCT®, and others)

47.8 million prescriptions were written for this thiazide diuretic in 2010. According to the JNC VII guidelines, this drug is a starting point for the pharmacologic management of uncomplicated hypertension. If and when the next set of guidelines are released, it remains to be seen if this drug will still play as prominent a role in blood pressure management. Earlier this year, as reported by theheart.org (free registration required to view most content) as study was published in the Journal of the American College of Cardiology that questioned the efficacy of the thiazide diuretics, not in decreasing blood pressure, but in reducing heart attack, stroke, or death, which is the whole reason for reducing blood pressure in the first place. When your patients are taking this drug, you should know be taking blood pressure. This is especially important when a patient starts taking this drug or any other blood-pressure lowering medication, when the dose of the drug is changed, or when another drug is added or removed from the patient’s regimen. Over the long-term, hydrochlorothiazide can produce some not-so-nice changes in blood lipids and blood glucose, perhaps resulting in new conditions, like type 2 diabetes, that also require pharmacologic management.

9. metformin hydrochloride (Glucophage®)

48.3 million prescriptions were written for metformin in 2010. This agent is a very common starting point for the management of type 2 diabetes. As far as the risk-benefit discussion goes, this is a pretty good drug. It lowers blood glucose but doesn’t do much else. Gastrointestinal upset and discomfort are common when the drug is first started. Patients using metformin aren’t likely to experience hypoglycemia from the drug and , unlike most other medications used to treat type 2 diabetes, metformin doesn’t promote weight gain – it tends to be weight neutral or even promote some weight loss. This makes it a great first choice in overweight or obese people who need to start managing blood glucose regulation problems with a medication in addition to diet and exercise.

8. amoxicillin (many trade names)

52.3 million prescriptions

7. azithromycin (Zithromax®)

52.6 million prescriptions

That’s 105 million antibiotic prescriptions, but there’s not much for us to worry about with these 2 agents in relation to rehabilitation. Gastrointestinal upset and hypersensitivity are the 2 most common problems linked to antibiotic use. You should know your patient is being treated for an infection and if you notice any skin changes, or the appearance of a rash, it would be important to ask your patient about antibiotic use, as skin reactions can, albeit only rarely, become extremely serious.

6. omeprazole (Prilosec®)

While this drug is also available over-the-counter, it ranked sixth last year as providers wrote 53.4 million prescriptions for its use. Omeprazole is used most commonly in the management of gastro-esophageal reflux disease and peptic ulcer disease. It inhibits some of the liver enzymes that metabolize drugs and interacts with other medications that depend on these enzymes for their breakdown. Omeprazole may impact bone health when it’s taken at high doses over the long-term. Hip fracture is more common in individuals who take  a lot of omeprazole for a long time. “Long-term” in this case means for more than a year. “High doses” is a little less clear, and seems to have been measured as the number of times per day the drug is taken (once or twice) rather than the actual dose. Perhaps changing the pH of the GI tract has an effect on calcium absorption, the link between the drugs, bone health, and fracture is not crystal clear at this point. Additionally, this drug is used to prevent ulcers in patients who are in intensive care, but its use is associated with an increased incidence of pneumonia.

5. amlodipine besylate (Norvasc®)

A very common anti-hypertensive that is also used to treat ischemic symptoms of coronary artery disease, 57.2 million prescriptions were written for this drug last year. As with hydrochlorothiazide, monitor blood pressure. This will be most important soon after treatment with the drug has been started, and whenever another drug is added or taken away, even over-the-counter medicines. The peripheral vasodilation produced by amlodipine and other drugs like it often causes peripheral edema.

4. levothyroxine sodium (Synthroid®)

70.5 million prescriptions were written for this synthetic version of thyroxine, also known as T4. There are problems with having too little thyroid hormone and too much thyroid hormone. The object of replacement is to normalize levels of T4 in individuals with hypothyroidism. One would assume that if this normal level is maintained, there would not be issues associated with the use of levothyroxine. Of course, this assumption appears to be wrong. A study published in the British Medical Journal last week suggests that people requiring prolonged thyroid replacement are at increased risk for fracture. This will be the topic for a post in the near future. Taking too much levothyroxine produces symptoms of hyperthyroidism, including nervousness and irritability, tachycardia, hypertension, palpitations, weight loss, intolerance to heat, myalgia, weakness, and fatigue.

3. We’re in the top three now and coming in at number 3 with 87.4 million prescriptions in 2010 – lisinopril (Prinivil®)

Yet another blood-pressure lowerer, so once again, keep tabs on your patient’s blood pressure when this drug is added, the dose is changed, etc. The ACE inhibitors as a group very commonly produce a dry cough, once upon a time known among cardiologists as the “Vasotec tickle”. The cough isn’t an indication of any particular pulmonary pathology, but it may become bothersome enough to warrant a change in medication. The newer cousins of the ACE inhibitors, the angiotensin receptor blockers, or ARBs, don’t have this issue with cough and seem to be just as effective in most situations where ACE inhibitors would be used. The ARBs are quite a bit more expensive than their older cousins.

2. simvastatin (Zocor®)

As its name will tell you, this is one of seven statins currently available in the United States. Lots of people take it, to the tune of 94.1 million prescriptions last year. These drugs are really good at lowering low-density lipoprotein levels in the blood. Usually abbreviated LDL, this is also referred to as “bad cholesterol”, so it should make sense that a drug that lowers LDL would be widely used. High LDL levels are linked pretty strongly to bad sorts of cardiovascular disease outcomes – heart attack, stroke, and being dead. The major issue related to these medications that is important to physical therapists is their effect on muscle. The mechanism has yet to be clarified, but the statins are not good for muscle, especially exercising muscle. How often is this a problem? We don’t really know. But if only 1% of statin users are affected, this is still a lot of patients. It’s important enough that 2 papers have been published in Physical Therapy in the last few years.[1,2] Bottom line: with unexplained weakness, myalgia, or other impairments in muscle performance in a patient taking a statin, have a conversation with the patient, and then the patient’s physician about addressing the issue.

And the Number 1 Medication of 2010, with 37 million more prescriptions than the runner up, prescribed 131.2 million times, is…

hydrocodone/acetaminophen (Vicodin®)

There’s been a fair amount of attention in the medical media lately given to both opioids (hydrocodone) and acetaminophen (acetaminophen). Certainly there is the potential for misuse, abuse, and addiction with opioid pain relievers and this is a real problem for prescribers of these medications. Overall safety is a problem for opioid users. Acetaminophen, the active ingredient in Tylenol, is a common pain reliever found in many prescription and over-the-counter medications. Taking too much of it happens to be one of the most common causes of liver failure in the United States. From a rehabilitation point of view, opioids contribute to fall risk, especially in older adults. Acetaminophen is an important example of the significance of other-the-counter medications, and the importance of health care providers having an awareness of all of the medications a patient is taking, not just the prescription drugs. Many of these could contain acetaminophen, and, without the patient being aware, could result in the unintentional over-consumption of the drug. Know what your patients are taking, and find out what they know about what they are taking.

There you have it, the Top 10 Drugs for 2010. There’s a good chance many of your patients are using these medications. Drugs do things to your patients – even in rehabilitation, you should understand what those things are and how they might impact your patient, your practice, and your clinical decision making.

Back to text
1. Tomlinson SS, Mangione KK. Potential adverse effects of statins on muscle. Phys Ther. 2005;85:459-465.
2. Di Stasi SL, MacLeod TD, Winters JD, Binder-Macleod SA. Effects of statins on skeletal muscle: a perspective for physical therapists. Phys Ther. 2010;90:1530-1542.

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Your patients might not know what you think they do about their medications

There’s an interesting and informative medical blog out there called Clinical Cases and Images: Casesblog that I follow in my RSS reader and it recently pointed me to a paper published in the Archives of Internal Medicine in 2006.[1] The authors of the study combined information from surveys of patients and physicians with the coding of transcribed audiotapes of office visits with a variety of physicians – family physicians, cardiologists, and internists, in order to quantify the quality and types of information patients typically receive about newly prescribed medications.

I think most physical therapists assume that patients understand something about each of the medications they take. Or at the very least, that the patients were informed about the medications when the drugs were prescribed. This study questions that assumption.

What would you want your patients to know about their medications? The medication name? Check (duh). The reason the patient should take the drug? Check. How long the patient should use the drug? Yep. The adverse effects of the drug? Check. The number of tablets to be taken and the frequency or timing of taking them? Check, double check (duh again).  These are exactly the questions the investigators tracked during 860 office visits of 909 patients. New medicines were prescribed during 185 of these visits and the audiotapes and surveys of the patients and physicians involved in the visits served as the data used in the analysis.

What did they find? They found that our assumption that patients have been told about their medications by the physicians prescribing them is a dangerous one:

  • 13% of the time, physicians didn’t provide their patients with a justification for taking the medication
  • 66% of the time, patients weren’t told if or when medications could be stopped
  • 45% of the time, patients weren’t told how many tablets to take or sprays to use
  • 42% of the time, patients weren’t told how often to take a new medication
  • 65% of the time, patients weren’t told about adverse effects they might expect

All in all, physicians failed to communicate almost 40% of the expected information about new medicines to patients. If the recommended drug was available over-the-counter, patients were only provided with 50% of the information they’d need to use the drug correctly and understand why they needed to take it.

Certainly, patients get information about their medications from sources other than the prescribing provider. Pharmacists and drug packaging probably supply some of that knowledge. But it is clear to see that all sorts of problems might arise if patients don’t understand why and how they should take their medications. Get that medication history from your patient, but make no assumptions that it makes sense,  and no assumptions that your patient is taking those medications as they were prescribed. If it doesn’t make sense to you, ask.

Back to text 1. Tarn DM et al. Physician communication when prescribing new medications. Arch Int Med. 2006;166:1855-1862.

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…pssssssst… your patients are on drugs.

These are your patients:

Bustling by eskimo_jo

These are your patients on drugs:

Bustling by eskimo_jo

They look the same, don’t they? That’s because nearly all of your patients – young or old, athletes or critically ill – use some substance that changes their physiology. That substance may have been prescribed by another health care professional, but it might have been purchased over-the-counter, or it might be a relatively loosely regulated nutritional supplement. In any case, physiology changes in response to the presence of these molecules in the body. I’m sure most of you wouldn’t question the need for PTs to understand the implications of diabetes, multiple sclerosis, or asthma on patient/client management. Your examination of the patient, your choice of interventions, your evaluation of the patient’s response – any or all of these might be affected by a disease process. Well, it turns out that your management might be affected in the same way by drugs that patients are taking. Because they change physiology. Just like pathology.

I’m not implying that PTs should understand everything about every drug. We don’t prescribe, after all, at least not the vast majority of us. But I do believe there is some important overlap between pharmacology and function, and that is what I intend to write about here. My goals are to catch your interest, make you think about your practice and your clinical decision-making, generate some discussion, and to help you make the best decisions that you can for your patients.

I do not intend to drift off into a drug-bashing frenzy and certainly am not looking to “physician-bash”. There are many valuable medications that keep our patients alive and improve their function. But when it comes to drugs, we take the good with the bad, and need to be aware of what “the bad” might be. And physicians and other prescribers, along with PTs, are human and make mistakes. How we respond when we think a mistake has been made is the key. As another set of eyes and ears, we can listen to our patients and use our observation skills as advocates for patient safety when it comes to medications. So, I’ll try to keep you up to date as best I can when and where pharmacology intersects with function.

Check back in soon.

Photo by eskimo_jo, available under a Creative Commons Attribution-NonCommercial-NoDerivs license.

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