Polypharmacy as a Risk Factor in the Treatment of Type 2 Diabetes

Austin, Roger P.

doi:10.2337/diaspect.19.1.13

Cited by 57 publications

(60 citation statements)

References 17 publications

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“…[11] However, reduction in number of drug might cause under treatment, specially in T2DM patients with dyslipidemia, resulting in serious consequences. [10] Thus, pharmacist may have significant role on optimization of the drug and dosage regimen for maximum benefit of patient.…”

Section: Discussionmentioning

confidence: 99%

Adverse Effects of Oral Hypoglycemic Agents and Adherence to them among Patients with Type 2 Diabetes Mellitus in Nepal

Shrestha

Prajapati

et al. 2017

J Lumbini Med Coll

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ABSTRACT:Introduction: Oral hypoglycemic agents (OHAs) are the most common drugs used in Type 2 Diabetes Mellitus. There are various established adverse effects related to their use including hypoglycemia, weight gain, gastrointestinal disturbance, lactic acidosis, and fluid retention. However, the pattern of adverse effects related to OHAs in Nepalese patients still needs to be explored. Our study aims to determine the pattern of adverse effects resulting from the use of OHAs among Type 2 Diabetes mellitus patients and their adherence to the medication. Methods: All diabetic patients who met the inclusion criteria were enrolled in the study. After informed consent, patients were interviewed and evaluated as per the designed proforma. They were mainly studied for common drug used, adverse effects of the drugs, occurrence of hypoglycemia, and adherence to treatment. Results: The study comprised of 183 patients with mean age of 58.73 years (SD = 12.95). Fifty-six (30.6%) patients said that they developed adverse effects of drugs but only 21 (11.5%) of them reported to their treating physician. Most common adverse effect were related to central nervous system such as tingling sensation of hands and feet, dizziness, drowsiness, etc. Though 91 (49.7%) patients had developed symptoms suggestive of hypoglycemia, only 31 (16.9%) knew that it was due to hypoglycemia. Majority of the patients (n = 143, 78.1%) administered the drugs as prescribed by the physician. Among the defaulters, the most important reasons for failure to properly administer the drugs was forgetfulness in 82.5% (n = 33, N = 40) of cases. Among the study variables family history of chronic illness (p = 0.046) and information about adverse effects from physician (p = 0.001) had a significant relationship with incidence of adverse effects. Whereas none of them had a significant relationship with adherence to hypoglycemic medication. Conclusion: The incidence of adverse effects was high with hypoglycemia occurring in 49.7% of the cases, though only one-third of them recognized it to be due to hypoglycemia, in the patients with Type 2 Diabetes Mellitus. Family history of chronic illness and information about adverse effects from the physician had significant relationship with the incidence of adverse effects of hypoglycemic treatment.

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Section: Discussionmentioning

confidence: 99%

Adverse Effects of Oral Hypoglycemic Agents and Adherence to them among Patients with Type 2 Diabetes Mellitus in Nepal

Shrestha

Prajapati

et al. 2017

J Lumbini Med Coll

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“…However, polypharmacy in these treatment regimens has been cited as a potential additional risk factor (2), with many patients on 4 or more concomitant medications. A more effective strategy would be to use a single agent that possesses combined benefits from simultaneous inhibition or stimulation of several related targets, without the risks associated with combination therapy.…”

mentioning

confidence: 99%

Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent

Artis¹,

Lin²,

Zhang³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

135

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In a search for more effective anti-diabetic treatment, we used a process coupling low-affinity biochemical screening with highthroughput co-crystallography in the design of a series of compounds that selectively modulate the activities of all three peroxisome proliferator-activated receptors (PPARs), PPAR␣, PPAR␥, and PPAR␦. Transcriptional transactivation assays were used to select compounds from this chemical series with a bias toward partial agonism toward PPAR␥, to circumvent the clinically observed side effects of full PPAR␥ agonists. Co-crystallographic characterization of the lead molecule, indeglitazar, in complex with each of the 3 PPARs revealed the structural basis for its PPAR pan-activity and its partial agonistic response toward PPAR␥. Compared with full PPAR␥-agonists, indeglitazar is less potent in promoting adipocyte differentiation and only partially effective in stimulating adiponectin gene expression. Evaluation of the compound in vivo confirmed the reduced adiponectin response in animal models of obesity and diabetes while revealing strong beneficial effects on glucose, triglycerides, cholesterol, body weight, and other metabolic parameters. Indeglitazar has now progressed to Phase II clinical evaluations for Type 2 diabetes mellitus (T2DM).adiponectin ͉ diabetes ͉ partial agonist ͉ PPAR pan-agonist ͉ Scaffold-based drug discovery T herapeutic approaches to Type 2 diabetes mellitus (T2DM), which currently affects Ϸ6% of adults in the United States (US Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA; 2005), are generally polypharmaceutical in nature, targeting effects on insulin sensitivity and elements of the coincident dyslipidemia and cardiovascular diseases (1). However, polypharmacy in these treatment regimens has been cited as a potential additional risk factor (2), with many patients on 4 or more concomitant medications. A more effective strategy would be to use a single agent that possesses combined benefits from simultaneous inhibition or stimulation of several related targets, without the risks associated with combination therapy. However, optimizing activities against several targets is a complex design problem that necessitates judicious choice of targets and requires new ways in which therapeutic agents are generated.Two classes of marketed therapeutics, the fibrates (as lipidlowering agents) and the glitazones (as insulin-sensitizing drugs) target related receptors known as PPAR␣ and PPAR␥, respectively, whereas a third member of the subfamily, PPAR␦, has been the target of intense preclinical interest as an avenue for treatment of dyslipidemia (3). A pan-agonist, capable of stimulating the 3 peroxisome proliferator-activated receptors (PPARs) as a group, would be expected to be particularly useful in the treatment of T2DM from the standpoints of both efficacy and reduction in the additional risk factors associated with polypharmacy. Despite the close structural relationship between these 3 receptors, the search for compounds whi...

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“…These findings are on par with other studies which show that medication classes most commonly associated in polypharmacy are those for the cardiovascular system and alimentary tract (Aparasu et al, 2005;Hovstadius & Petersson, 2012;Hovstadius & Petersson, 2013), and diabetes Austin, 2006). These finding are not surprising as therapy with multiple drugs has become the standard medication therapy of care for chronic diseases such as diabetes (Ismail-Beigi, 2012) and hypertension (NHFA, 2010).…”

Section: Polypharmacy and Gendersupporting

confidence: 69%

“…Diabetes has been found to be associated with polypharmacy in all adult age groups, while hypertension is associated with polypharmacy in people aged 30-49 and 50-64 years (Moen et al, 2009). Insomnia has also been found to be associated with polypharmacy (Bin, Marshall & Glozier, 2012;Austin, 2006). Finally, as discussed in the previous chapter, at a policy level the PBS medication subsidy provided to patients in an effort to improve access to essential medicines may also be inadvertently promoting polypharmacy.…”

Section: Multiple Medication Usementioning

confidence: 92%

Patterns of medication use in Queensland Australia and the impact of a large copayment increase: an exploratory study

Balram¹

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Polypharmacy as a Risk Factor in the Treatment of Type 2 Diabetes

Cited by 57 publications

References 17 publications

Adverse Effects of Oral Hypoglycemic Agents and Adherence to them among Patients with Type 2 Diabetes Mellitus in Nepal

Adverse Effects of Oral Hypoglycemic Agents and Adherence to them among Patients with Type 2 Diabetes Mellitus in Nepal

Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent

Patterns of medication use in Queensland Australia and the impact of a large copayment increase: an exploratory study

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