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Module 9. Common Drugs that Affect Diabetes Control

Introduction

Even the most seasoned health care providers (HCPs) have found diabetes to be among the most challenging diseases to manage. The difficulties arise from the dynamic nature of this disease state, the lack of patient knowledge about the potential side effects of treatment, and the relatively common practice of nonadherence. Type 2 diabetes mellitus (T2DM), in particular, is progressive and, as the disease advances, patients are forced to evolve with it or risk long-term adverse patient outcomes. Even when the appropriate therapy is chosen, there is still the significant risk of medication side effects and interactions. Pharmacists are acutely attuned to the risks of medication use; but, with dozens of possible medications and even more supplements, sometimes choosing from this seemingly overwhelming sea of treatment options can be intimidating. The purpose of this module is to provide education to help you understand how multiple medications in patients with diabetes can affect blood glucose (BG) metabolism.

Prescription-drug use among adults has risen substantially in the United States (U.S.) since 1999. In a 2013 report, the most substantial increases in prescription-drug use were seen in patients 40 to 65 years of age and those aged 65 years and older.1 The most commonly prescribed medications, not surprisingly, were for hypertension, hyperlipidemia, diabetes, and depression. With so many new interventions and so many drugs coming off patent, polypharmacy (i.e., a patient on 5 or more clinically relevant agents) among those affected is now the new normal and it is part of the pharmacist’s role as a HCP to ensure that the combination of medications does not lead to negative outcomes.

There are multiple ways in which medications can impact diabetes control. Some medications may alter BG test results, creating false high or low blood-sugar readings. The detriment in this is obvious and could be quite serious. Other agents can cause substantial weight gain, leading to greater insulin resistance and subsequently higher BG levels. Drug interactions that might make the medications used for diabetes control more or less effective are also possible. The more medications a patient takes, the more likely he or she is to experience drug interactions that could cause harm. This point may seem intuitive, but it is something we should not forget or take lightly. One study by Nolan and O’Malley suggested that senior patients who were taking 10 or more medications had a 90%-plus probability of experiencing one or more drug interactions of clinical significance.2 This percentage may seem alarming, but it reinforces the concept that pharmacists must remain vigilant and well-educated while managing medication use, especially for frail and older adult patients. Pharmacists are the last line of defense between physicians trying to prescribe the right therapy and patients taking multiple agents that could interact and potentially cause them harm.

The Physiology of BG Metabolism

The first step toward a better understanding of diabetes and the medications that might affect control is to know the physiology of BG metabolism. This will allow for better recognition of the effects medications can have on BG control. Insulin is the main hormone involved in glucose regulation and homeostasis. It is released from the pancreatic beta cells in response to elevations in BG, thereby helping glucose become properly stored in the liver in the form of glycogen, which may be used when required. In addition, insulin allows the cells in the body to obtain energy by assisting carbohydrates and fats in becoming absorbed and used effectively. Insulin signals glucose-transport proteins to help distribute glucose throughout the body efficiently. These glucose-transport proteins are dependent on adequate potassium to do their job; so, if potassium is low, glucose metabolism may be affected. Increased body fat will also interfere with insulin action, causing resistance to the action of the hormone, making it more difficult to properly keep BG in balance. Glucagon is the opposing hormone to insulin and is also produced in the pancrase, thereby inducing gluconeogenesis and other mechanisms to raise BG in response to hypoglycemia.

It is not possible in the scope of this activity to cover every medication that may affect BG metabolism. This activity, though, will highlight some of the more common medications traditionally used in practice. Keep in mind that medications and/or factors that can alter BG metabolism and raise blood sugars may have the potential to affect patients with existing diabetes and may also create conditions that lead to new-onset diabetes in certain at-risk individuals.

Conditions That Affect Tests to Monitor Diabetes

The blood test for glycosylated hemoglobin (HbA1c) allows HCPs to have an indicator of glycemic control over a period of approximately 3 months and has become the standard-of-care measure for how well patients are controlling their diabetes. HbA1c is a stable glycoprotein formed when glucose binds to hemoglobin in the blood. The average life span of a red blood cell (RBC) is approximately 3 months, which is why HbA1c is a measure indicative of a 3-month period.3 This test is also used to help confirm a diagnosis of diabetes, as well as assess a patient with diabetes to determine therapy goals. The American Diabetes Association (ADA) has stated that an A1C level of 7 or lower is a basic target for adult patients with diabetes. Some major clinical trials, such as the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) determined that good diabetes control, as indicated by a lower HbA1c level, correlated with fewer complications in a patient with diabetes.4 Therefore, it is crucial that the HbA1c level drawn and measured is accurate. If this level is artificially higher or lower, it will inappropriately change therapy. The HbA1c level can be affected by any process that lowers the life span of RBCs or makes a higher percentage of young RBCs. Processes, such as acute blood loss or hemolysis, can dramatically alter the age range of circulating RBCs, which will cause an inaccurate HbA1c reading.5

Iron deficiency anemia is seen in practice as the result of multiple factors, including small bleeds, such as those caused by ulcers for example, and sometimes even dietary deficits. This type of anemia can cause HbA1c levels to be falsely elevated.6 It is also important to note that diabetes is a major cause of end-stage renal disease, with anemia being common in this patient population because the kidneys control RBC production.

Hemolysis is a condition that reduces the RBC life span, which increases the proportion of younger, less mature RBCs.6 If that life span is reduced, the resultant A1C value can be falsely lowered. Drug-induced immune-mediated hemolysis is rare, but should not be overlooked. Common drugs, which range from antibiotics like penicillin to Parkinson’s disease treatments like methyldopa (Aldomet) and levodopa (Dopar), can cause this reaction. Even more common medications—ibuprofen (Motrin), diclofenac (Cambia, Cataflam, Solaraze, Voltaren, Zorvolex), and cephalosporins—have been implicated. Importantly, take a closer look at a patient profile if an individual experiences a sudden unexpected change in his or her HbA1c level. If this occurs, a practitioner has to be aware that hemolysis may be contributory, so further work-up should be done.7-9 Drugs that are commonly associated with bleeding include nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, meaning that patients on these medications who have changes in their bowel habits and HbA1c levels also warrant further evaluation.10

Second-Generation Antipsychotics

Medications alter more than just how we measure glycemic control. Certain drugs have been shown to dramatically affect glycemic control itself. A large population of patients with diabetes experience depression or other forms of mental illness. Overall, people with T2DM have a 2-fold higher incidence of depression than the general population, with 1 study finding occurrences in 24% of women and 13% of men.11,12 Depression is a major comorbid condition, so we should be aware of the potential side effects of agents commonly used to treat psychiatric illnesses.

The second-generation antipsychotic medications are notorious for negatively affecting blood sugars and this class of agents has even been implicated as a cause of new-onset diabetes for some patients. These drugs initially were touted as being better tolerated by patients because they were associated with fewer extrapyramidal adverse events. The lower risk for these negative side effects came with a cost, however. These medications are strongly associated with accelerated weight gain, insulin resistance, diabetes, dyslipidemia, and increased cardiovascular risk. These adverse effects can develop in as few as 6 months after the initiation of pharmacotherapy for those without preexisting diabetes.13 Second-generation antipsychotic medications may cause abnormal glucose metabolism that can lead to insulin resistance and T2DM; therefore, it is imperative that patients with severe mental illness who are placed on chronic antipsychotic medications, such as those listed in Table 1, be screened for diabetes.14 Pharmacists can assist with identifying individuals who may be appropriate for screening, thereby helping with an early diagnosis. A consensus statement has been developed by the ADA, in conjunction with other professional organizations, which provides recommendations for monitoring fasting BG levels for 12 weeks after starting therapy and annually, thereafter, for patients without preexisting diabetes.15 If blood sugars move out of acceptable ranges, it may be prudent to switch a patient to an antipsychotic, such as aripiprazole or ziprasidone, that is less likely to cause abnormalities in blood sugars.

Table 1
First-Generation Antipsychotics Second-Generation Antipsychotics
Chlorpromazine (Largactil, Thorazine) Aripiprazole (Abilify)
Trifluoperazine (Stelazine) Olanzapine (Lanzek, Ozace, Zypadhera, Zyprexa)
Perphenazine (Trilafon) Quetiapine (Seroquel)
Haloperidol (Haldol) Paliperidone (Invega)
Thioridazine (Mellaril) Ziprasidone (Geodon, Zeldox)
Fluphenazine (Modecate, Prolixin) Risperidone (Risperdal, Zepidone)
  Clozapine (Clozaril)

For those patients who have already been diagnosed with diabetes and who are being prescribed antipsychotic medications for the first time, it is important to discuss possible changes in diabetes control with them. The second-generation antipsychotic medications, as stated, are of particular concern. It is known that some antipsychotic agents cause weight gain, which, of course, affects insulin resistance.16 The increase in weight caused by antipsychotic medications is often unpredictable. Clozapine (Clozaril) and olanzapine (Lanzek, Ozace, Zypadhera, Zyprexa) cause the greatest rise in weight, while aripiprazole (Abilify) leads to less of a gain.17 There seem to be other mechanisms, besides weight gain, that are involved in the development of diabetes in patients using some antipsychotic medications, but these have not yet been fully elucidated. Table 2 shows the extent to which some of these medications can cause an increase in weight and possibly alter lipid metabolism as well.

Although the risk of developing diabetes is high for individuals on antipsychotic medications, there is not enough screening of these patients. In late 2003, the U.S. Food and Drug Administration (FDA) announced that it was requiring class warnings to be added to the labeling of atypical or second-generation antipsychotic drugs, describing increased risks of hyperglycemia and diabetes. In some cases, the hyperglycemia was profound and subsequently associated with ketoacidosis, hyperosmolar coma, or death.18 The results of a recent time-series analysis of over 100,000 Medicaid patients who are taking second-generation antipsychotic medications showed that, despite the warning announced by the FDA, most individuals do not typically receive baseline serum glucose and lipid testing.19 There has to be better screening, and that starts with educating both HCPs and patients. Keep in mind that these drugs have helped thousands of people to overcome severe mental illness, so careful attention to the benefit-versus-risk profile is a must for patients on these medications. There are no absolutes in medicine, so all warnings and precautions have to be heeded.

Table 2
Chol = cholesterol; HDL = high-density lipoprotein; LDL= low-density lipoprotein

Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302(16):1765-1773.

Lipid-Lowering Agents

Another class of medications that has been shown to interfere with diabetes control is that of the lipid-lowering drugs—specifically niacin (Niacor, Niaspan) or nicotinic acid, which has been commonly used in the management of hyperlipidemia and focuses directly on triglycerides. Diabetes and the metabolic syndrome are associated with elevated lipid profiles, so many of your patients with diabetes may use some form of either prescription or over-the-counter niacin. In several studies, though, niacin has been reported to worsen diabetes control.20

One 16-week study that can be referenced concerning the effects of niacin at different doses on BG control involved 148 patients with diabetes and evaluated such control as one of the endpoints. The higher doses of niacin – 1000 to 1500 mg daily – resulted in an average HbA1c increase of 0.3%. A recent meta-analysis of niacin users that looked at cardiac risk and diabetes risk endpoints showed niacin therapy to be associated with a moderately increased risk of developing the disease regardless of background statin.20 These results indicate we also have to be more diligent at screening patients on niacin for new-onset diabetes, though no official recommendations have been published yet.

Niacin is not the only lipid-lowering agent that interferes with glycemic control. Statins, which are the most commonly prescribed medication for high cholesterol, have also been implicated in altering glucose metabolism. In 2012, the FDA released changes in statin safety labels to include those agents that have been found to increase HbA1c and fasting serum glucose levels. Numerous studies that were done to ascertain a reduction in cardiac risk factors also found that statins have diabetogenic potential and the effect varies with the dosage and type used.21 The exact mechanisms have not yet been fully fleshed out, but some have proposed that statins downregulate glucose transporters. Statins have also been shown to worsen diabetes control in patients with preexisting disease, but these effects appear to be minimal, with solid evidence not yet available.

Immunosuppressants: Corticosteroids and Transplant-Related Regimens

Perhaps the most notorious offending drug class of medications for altering glucose metabolism in patients with diabetes and prediabetes are corticosteroids, which come in the form of oral and inhaled medications as well as injectables in the hospital setting. Oral and intravenous corticosteroids in some circumstances are unavoidable; they are excellent medications for treating inflammatory or autoimmune conditions, such as chronic obstructive pulmonary disease exacerbations, asthma, vasculitis, or even severe osteoarthritis. With that said, it is even more of a necessity to understand the effect these drugs have on diabetes control and to counsel patients accordingly.

The mechanisms for the influence of corticosteroids on glucose regulation are complex and multifactorial. Glucocorticoids promote gluconeogenesis in liver and decrease glucose uptake and utilization by antagonizing the insulin response in skeletal muscle and fat tissue. Glucocorticoids also regulate glycogen metabolism in the liver by increasing glycogen storage. In skeletal muscle, glucocorticoids permit the breakdown of glycogen, thereby resulting in higher circulating levels of glucose. Even more importantly, glucocorticoids directly modulate the function of pancreatic alpha and beta cells that normally regulate the secretion of glucagon and insulin.22 During a normal stress response, the body has to have excess glucose immediately. But when this pathway is artificially stimulated, it can lead to cataclysmic effects on glycemic control, commonly making glucose levels uncontrollable in a patient with diabetes within hours of starting on an oral corticosteroid. It is incumbent on the pharmacist to advise patients with diabetes that their blood sugar control will probably change, so a plan should be in place to modify insulin dosing or medication, if necessary, after collaborating with their primary care practitioner.

There have been myriad studies illustrating the correlation between hyperglycemia and corticosteroid use. In 1 such study of patients with rheumatoid arthritis, nearly 9% developed diabetes within the 2 years after starting glucocorticoid therapy, which was significantly higher than the control group not on corticosteroid therapy.23 Another study showed that in patients without diabetes but with primary renal disease treated with prednisolone, 42% were found to have 2-hour post-lunch plasma glucose concentrations higher than 200 mg/dL, although they had normal fasting glucose levels prior to starting the corticosteroid. In a case-controlled study, the odds ratio of starting an oral hypoglycemic agent or insulin was 1.77 for those receiving a hydrocortisone-equivalent dose of 1 to 39 mg/day, 3.02 for 40 to 79 mg/day, 5.82 for 80 to 119 mg/day, and 10.34 for 120 mg/day or more.24,25 For people who will require chronic immune suppression with corticosteroids after transplantation, there are published guidelines on managing glucocorticoid-related diabetes. Guidelines suggest checking the fasting plasma glucose level once a week for the first 4 weeks after transplantation, then at 3 months, then at 6 months, and then once a year thereafter.26 Diabetes is the leading cause of end-stage renal disease (ESRD) in the U.S., accounting for more than 44% of all patients with ESRD. Transplantation is recommended, if possible, over dialysis because of improved morbidity and mortality.27

It is also important to note that new-onset diabetes after transplantation, often referred to in the literature as the acronym NODAT, is a serious complication. Once again it is evident that certain medications have the ability to either potentially worsen diabetes control or actually cause new-onset diabetes in patients. It appears that immunosuppressant therapy in addition to oral corticosteroids may act as triggers in developing diabetes in certain at-risk individuals, where risk factors such as age, family history, and certain antibody titers are measured.28 Different drugs were studied and compared for their ability to potentially contribute to new-onset diabetes for patients who have had a transplant. Though all antirejection agents can have an effect on BG metabolism, some may affect BG more than others. For example, cyclosporine was less diabetogenic than tacrolimus. Transplant patients are on complex drug regimens and must be monitored frequently for disease progression and signs of rejection.

Antihypertensive Medications

Approximately one-third of all adults in the U.S. have hypertension, and that number continues to grow with our aging population. The number of adults with high blood pressure (BP) grew from about 59 million to more than 70 million over the past decade. More important to this discussion is that from 2009 to 2012, of those 18 years of age or older with diagnosed diabetes, 71% had BP higher than or equal to 140/90 mm Hg.29 With so many patients with diabetes being treated for hypertension, it is quite common to see a prescription for a thiazide diuretic on a patient profile.

Thiazide diuretics have been implicated in causing hyperglycemia in patients with diabetes and also contributing to new-onset diabetes in some individuals. The exact mechanism of how thiazide diuretics cause alterations in BG metabolism is poorly understood and the science behind alterations in transporters is beyond the scope of this module. Some theories that have been postulated include worsening of insulin resistance, decreasing insulin release, lowering serum potassium, and activating the renin angiotensin-aldosterone system.30 Hydrochlorothiazide has been implicated as a cause of new-onset diabetes in as few as 9 to 18 weeks after initiation of therapy. Keeping patients on a lower dose of hydrochlorothiazide (12.5 to 25 mg) may help ameliorate the chances of blood sugar issues in patients with or without preexisting diabetes. HCPs may also opt to choose a different class of medication or a potassium-sparing diuretic if diabetes and hyperglycemia are concerns.31,32

Beta-blockers are another class of antihypertensive agents that, like thiazide diuretics, have been found to raise the risk of developing diabetes and possibly affect blood sugar control in patients with diabetes. As pharmacists, we have always been taught that beta-blockers can mask the signs of hypoglycemia by slowing the heart rate and blunting sympathetic response to low blood sugar. The main mechanism for increasing insulin resistance is vasoconstriction of small blood vessels in muscle tissue, which impairs glucose transport across the vascular membrane.33 New-onset diabetes is also increased in those on beta-blockers by more than 30% for yet-to-be-clarified reasons. While beta-blockers have a profoundly positive effect on reducing cardiac morbidity and mortality, we cannot forget the consequences of these medications on glycemic control and act accordingly.34

HIV Medications

Protease inhibitors (PIs) are a mainstay of HIV therapy and this category of medications has been shown to cause hyperglycemia in patients with and without diabetes. PIs acutely and reversibly inhibit the insulin-responsive glucose transporter Glut 4, in turn leading to peripheral insulin resistance and impaired glucose tolerance.35 Animal models have also shown direct pancreatic beta-cell dysfunction.36

Antibiotics

Those with diabetes are more prone to infections than those without the disease. Persistent hyperglycemia creates an environment ripe for bacteria to grow and a suppressed immune system in these patients significantly heightens the risk of serious infection for those with diabetes over the general population.37 Therefore, antibiotics are often a staple of therapy for most people with diabetes at some time in their lives. Thus, it is crucial to realize that certain antibiotics may cause serious BG fluctuations in this group of patients.

There is also an elevated risk of BG fluctuations in patients with diabetes who take fluoroquinolones, as shown by a study that involved over 78,000 people with diabetes in Taiwan. The study looked at these patients’ use of the following 3 classes of antibiotics: fluoroquinolones, macrolides, and cephalosporins. An endpoint was any emergency-department list or hospitalization for severe blood sugar swings within 1 month (30 days) after starting the antibiotics.38 The study’s results showed that those patients on fluoroquinolones were more likely to experience severe blood sugar swings than those who took other classes of antibiotics. The odds of severe hypoglycemia and hyperglycemia were significantly greater with (levofloxacin (Levaquin), but not ciprofloxacin (Cipro, Cipro XR, Proquin XR), than with azithromycin (Zithromax, Zmax). Moxifloxacin (Avelox, Vigamox) was implicated as causing the highest risk for hypoglycemia.39

To learn how the fluoroquinolone class causes these metabolic derangements, the studies referenced above point toward the important role of the adenosine triphosphate (ATP)-sensitive K+ channels in the pancreatic beta cell and the importance of anti-insulin hormones. In any event, this study shows that caution should be exercised when patients with diabetes are started on any fluoroquinolone.

In addition, a recent study done at the University of Texas linked metronidazole (Flagyl, Metrogel, Noritate), fluconazole (Diflucan), and sulfamethoxazole-trimethoprim (Zotrim) to episodes of hypoglycemia in patients with diabetes who were taking oral antihyperglycemic agents, such as glipizide (Glucotrol, Glucotrol XR) and glyburide (DiaBeta, Micronase). In conclusion, more frequent monitoring of blood sugars is recommended if a patient taking a sulfonylurea is also prescribed an antibiotic associated with hypoglycemia.40

Diabetes is a complex disease that requires a great deal of thought when evaluating blood sugars. If a patient with diabetes has an illness, his or her blood sugar will likely rise in response to the stress on the body. Once an antibiotic is given, it is possible that blood sugars will normalize because the patient is “getting better.” The above antibiotics may be useful for treating patients with diabetes and are certainly not contraindicated, but caution is advised in making sure blood sugar fluctuations are not extreme.

Other Common Drugs: Alcohol and Caffeine

The most commonly abused psychotropic drugs in the U.S. are actually caffeine and alcohol. The U.S. Department of Health and Human Services recommends a maximum of 1 drink per day for women and 2 drinks daily for men. A single drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of spirits. Excess alcohol consumption is dangerous enough for the general population, but adding diabetes to the equation makes the situation even more treacherous.41

While drinks do carry carbohydrate value, which can contribute to overall blood sugar control, one of the biggest issues with drinking and diabetes is the potential for hypoglycemia, where blood sugar drops too low. This risk can carry over for 8 to 10 hours after you drink alcohol. For most people, this risk for hypoglycemia happens at night, when the patient is most vulnerable. Alcohol becomes metabolized in the body in a manner that makes it especially dangerous for a patient with diabetes. When alcohol is ingested, most of the metabolic capacity of the liver is involved, so even if hypoglycemia is treated with complex carbohydrates, the effect may not manifest for hours. Also, glucagon will not work as effectively after alcohol consumption, thereby leading to an impaired sympathetic response to low blood sugar. To add to the confusion, alcohol’s neurologic effects may be confused with signs of hypoglycemia.42

Caffeine is certainly a staple of many people’s morning ritual. Consumption of this stimulant is known to raise blood pressure (BP), but caffeine has also been shown to potentially raise BG. Paradoxically, caffeine has also been lauded as possibly helping to prevent T2DM. There is really not enough evidence to show clear results either way because studies did not take into account other factors, such as how long a person has been consuming coffee or what types of coffee are consumed. A small study that was published in Diabetes Care in 2007 looked at the effects of black coffee on blood sugar levels. Higher glucose levels were found in those study participants given caffeine versus those given placebo.43 A proposed mechanism of caffeine thought to cause a rise blood sugars may involve the stimulant causing the release of epinephrine, which can increase BG through hormonal regulation. Interestingly enough, caffeine was theorized to help prevent the development of T2DM. Results at this point are inconclusive, so we should continue to preach moderation with this commonly used agent.

Conclusions

Patients with diabetes often have other comorbidities that must be treated as well. This often leads to polypharmacy, which has been defined as 1 patient on 5 or more clinically relevant prescription medications. Our senior population is growing, currently comprising some 14% of the U.S. population and making up approximately 34% of prescription-drug users.

With the expanding role of the pharmacist in the new health care landscape, it is incumbent on the pharmacist to identify potential adverse drug reactions (ADRs) and to report them when necessary. ADRs are the 4th leading cause of hospital admissions, which is significant because many of the ADRs are preventable. With medication therapy management (MTM) at the forefront of pharmacy practice, pharmacists can make a huge impact on the nation’s health. Regular documentation and identifying potential drug therapy issues will surely become the new business model.

The complexity of drug regimens in the patient with diabetes creates an increasing challenge for the pharmacist who is completing a Comprehensive Medication Review and identifying the person’s risks and benefits of medication therapy. Also, because of the increasing older adult population, medications that are appropriate for a given senior patient may be incorrectly dosed for that patient. In a study conducted at a Veterans Affairs Medical Center in Michigan, patients with diabetes were found to have experienced potentially dangerous hypoglycemia because their medications were potentially dosed too high.44

Senior citizens often require lower dosing of agents because they typically have lower body mass indexes and, therefore, metabolize drugs differently than younger patients. Lower dosing of medications in this ever-growing older patient population is often warranted.

As we have seen throughout this module, medications that cause alterations in BG are often implicated in new-onset diabetes, especially in those patients at high risk for developing the disease. It is important to know the symptoms of diabetes, which include polydipsia, polyuria, polyphagia, and sudden weight loss or frequent urinary tract infections. Armed with the proper information, we can all make interventions to potentially save lives.

Counseling Tips for Common Drugs that Affect Diabetes Control
Category Potential Counseling Tips
Testing
  • The blood test for glycosylated hemoglobin (HbA1c or A1C) is a measure of glycemic control over 3 months.
  • An A1C level of 7 or lower is a basic target for adult patients with diabetes.4
Conditions that can alter A1C readings
  • The HbA1c level can be affected by any process that lowers the life span of red blood cells (RBC) or makes a higher percentage of young RBCs. These conditions include Iron deficiency anemia among others.6
Medications that impact glycemic control
  • Certain drugs have been shown to impact glycemic control.
  • Medications that can negatively impact blood sugars include:  second-generation antipsychotic medications can negatively impact blood sugars, niacin, statins, transplant medications, certain blood pressure medications (e.g., thiazides and Beta-blockers), certain medications for HIV (human immunodeficiency virus), caffeine and alcohol. 

Update on Niacin Use

In 2016, the Food and Drug Administration (FDA) withdrew approval of the indications related to the coadministration of niacin extended-release (ER) tablets with a statin.1 This decision was based on results from two large clinical event trials, Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) and Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), which concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone.2 The ADA states that “Combination therapy (statin/niacin) has not been shown to provide additional cardiovascular benefit above statin therapy alone, may increase the risk of stroke with additional side effects, and is generally not recommended”.3

References:
1. https://www.federalregister.gov/documents/2016/04/18/2016-08887/abbvie-inc-et-al-withdrawal-of-approval-of-indications-related-to-the-coadministration-with-statins;
2. Superko HR, Zhao XQ, Hodis HN, Guyton JR. Niacin and heart disease prevention: Engraving its tombstone is a mistake. J Clin Lipidol. 2017;11(6):1309-1317;
3. American Diabetes Association. 9. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl. 1):S86–S104.

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