Robert S. Busch

Colesevelam Hydrochloride-Ezetimibe Combination Lipid-Lowering Therapy in Patients with Diabetes or Metabolic Syndrome and a History of Statin Intolerance

OBJECTIVE To determine the effectiveness and safety of colesevelam hydrochloride (HCl) and ezetimibe combination therapy in statin-intolerant patients with dyslipidemia and diabetes mellitus (DM) or metabolic syndrome (MS). METHODS We identified potential study subjects through a computerized text search of patient electronic medical records using the terms colesevelam, WelChol, ezetimibe, and Zetia. Medical records were subsequently reviewed to identify all patients with DM or MS. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride levels immediately before the initiation of therapy with colesevelam HCl (1.875 g twice a day) or ezetimibe (10 mg daily) were compared with those after a minimum of 3 months of single drug therapy and after a minimum of 3 months of combination therapy. Drug safety was evaluated by review of transaminase levels and reports of side effects or drug discontinuation. RESULTS The computerized search initially identified 91 electronic medical records; 16 patients fulfilled all study criteria. Baseline patient demographics included a mean age of 62.5 (+/-11.8) years and a mean body mass index of 31.4 (+/-5.2) kg/m2; 50% of patients were female, 75% had type 2 DM, and 25% had MS. In comparison with baseline, colesevelam HCl-ezetimibe combination therapy was associated with significant reductions in mean levels of total cholesterol (27.5%), LDL-C (42.2%), and non-HDL-C (37.1%). In addition, 50% of patients achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C target of less than 100 mg/dL. Therapy was well tolerated, with no significant changes in mean transaminase levels, no reports of myalgia, and no discontinuation of therapy. CONCLUSION Colesevelam HCl-ezetimibe combination therapy was associated with improved TC, LDL-C, and non-HDL-C lipid profiles and was well tolerated. Such therapy may be a reasonable consideration for statin-intolerant patients with DM or MS who have elevated cholesterol levels.

A Glucose Meter Accuracy and Precision Comparison: The FreeStyle Flash Versus the Accu-Chek Advantage, Accu-Chek Compact Plus, Ascensia Contour, and the BD Logic

BACKGROUND This study compared the accuracy and precision of five blood glucose (BG) meters. METHODS Diabetes patients undergoing venipuncture for glucose testing were randomized to one of two groups consisting of three meters: FreeStyle Flash (Abbott Diabetes Care, Alameda, CA), Accu-Chek Advantage (Roche Diagnostics Corp., Indianapolis, IN), and Accu-Chek Compact Plus (Roche Diagnostics) or FreeStyle Flash, Ascensia Contour (Bayer Healthcare, Diagnostic Division, Tarrytown, NY), and BD Logic (BD Diabetes Care, Franklin Lake, NJ). Within 5 min following venipuncture, duplicate finger BG measurements from three ipsilateral fingers were taken. Finger glucose measurements were compared with laboratory reference values. Accuracy was assessed by a Clarke error grid analysis (EGA) and within 10% of the laboratory value criteria. Meter precision was determined by calculating the absolute mean differences in glucose values between duplicate samples. RESULTS Finger sticks were obtained from 202 patients. Mean venipuncture BG was 148 mg/dL (SD +/- mg/64 dL; range 25-439 mg/dL). Accuracy by Clarke EGA (Zone A results) was demonstrated in 69% of Advantage samples, 75% of Compact Plus, and 96% of the first group of Flash versus 88% of the Contour, 67% of the Logic, and 91% of the second Flash samples (P < 0.05 for both Flash and Contour). Meter accuracy using the 10% criteria was demonstrated in 30%, 38%, 70%, 46%, 48%, and 68% of the samples, respectively (P < 0.05 for both Flash groups compared to each of the other meters). There were no differences in meter precision. CONCLUSIONS No statistically significant differences in accuracy were evident using the Clarke EGA criteria (pooled results of Zone A and B), though the more strict 20% accuracy criteria (Zone A results only) found the Flash and Contour to have significantly greater accuracy compared to the Advantage, Compact Plus, and the Logic. Using the 10% accuracy criteria found the Flash to have significantly greater accuracy than each of the other four meters. All five meters demonstrated similar precision.

The utility of oral diabetes medications in type 2 diabetes of the young.

BACKGROUND An estimated two-thirds of medications prescribed for use in pediatric patients have not been proven safe or effective for this patient population. Since 1995 a dozen orally administered diabetes medications or combination of medications for the management of type 2 diabetes mellitus have been approved by the Food and Drug Administration. Of these, only one (metformin) is approved for use in pediatrics. As the prevalence of children diagnosed with type 2 diabetes continues to rise, the need for adequate information regarding the safety, efficacy, and appropriate dosing of oral diabetes medications in the pediatric population likewise increases. OBJECTIVE The purpose of this paper is to present the data available regarding the use of oral diabetes medications in a pediatric type 2 diabetes population. METHODS A computerized literature search was performed using Medline and the Cochrane Database of Systematic Reviews. RESULTS The Table consists of a summary of data regarding the use of oral antidiabetic agents in pediatric patients. These data include information regarding drug safety and efficacy and/or drug pharmacokinetic and drug dosing information. CONCLUSIONS Data concerning the safety and efficacy of oral diabetes medications to treat type 2 diabetes of the young is limited. Data currently available support the use of metformin as first-line drug therapy. Results of prospective studies over the next three to five years will better define the role of thiazolidinedione use as initial therapy in pediatric type 2 diabetes patients.

Off‐Label Use of Exenatide for the Management of Insulin‐Resistant Type 1 Diabetes Mellitus in an Obese Patient with Human Immunodeficiency Virus Infection

Exenatide is an incretin mimetic indicated for the treatment of type 2 diabetes mellitus in combination with a sulfonylurea, a thiazolidinedione, metformin, or metformin plus a sulfonylurea or thiazolidinedione. Exenatide lowers postprandial blood glucose levels by stimulating glucose‐dependent insulin secretion, inhibiting glucagon secretion, slowing gastric emptying, and increasing satiety. Therapy with exenatide often results in weight loss, which further assists in decreasing insulin resistance. This feature makes the drug an attractive therapeutic option for obese patients. We report the successful off‐label use of exenatide in an obese, 40‐year‐old man with type 1 diabetes and human immunodeficiency virus (HIV) infection who had gastrointestinal intolerance to pramlintide. The patient had experienced a dramatic weight gain secondary to his antiretroviral drugs. This weight gain led to insulin resistance and the development of type 2 diabetes; thus he had characteristics of both types 1 and 2 diabetes, or double diabetes. Before the start of exenatide therapy, he weighed 123 kg, had a body mass index of 42.3 kg/m2, and had a suboptimal hemoglobin A1c value of 8.7%. After 11 months of therapy, the patient lost 24 kg (19.5% of his body weight) and achieved a hemoglobin A1c value of 7.3%. His basal insulin requirement was reduced by 25%, and his use of short‐acting insulin before breakfast and before dinner was discontinued. In addition, the patients quality of life substantially improved, as he was able to return to work and exercise after being nearly incapacitated by his weight. To our knowledge, this is the first published case report of the use of exenatide in a patient with type 1 diabetes mellitus or human immunodeficiency virus infection. Given this experience, exenatide may prove to be a useful alternative in selected patients with type 1 diabetes.

SGLT-2 INHIBITOR THERAPY ADDED TO GLP-1 AGONIST THERAPY IN THE MANAGEMENT OF T2DM.

OBJECTIVE To assess the real-world efficacy and safety of canagliflozin therapy added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1 year of glucagon-like peptide-1 (GLP-1) agonist therapy. METHODS This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who received GLP-1 agonist therapy for a minimum of 12 months. The primary study outcome was change in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints included changes in average weight, and comparison of the percentage of patients obtaining an HbA1c <7%. RESULTS A total of 75 patients met all the study criteria. Baseline patient characteristics were as follows: average age, 58 ± 9 years; mean duration of T2DM, 14 ± 6 years; 56% male; 92% Caucasian; baseline body mass index (BMI), 39.4 ± 9.4 kg/m(2); and mean baseline HbA1c, 7.94 ± 0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg, respectively. Adverse effects were reported by 13 (17.3%) patients, including 4 (5.3%) who discontinued canagliflozin because of adverse reactions. CONCLUSION Canagliflozin was generally well tolerated and significantly further reduced mean HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.

Cholesterol and Glycemic Effects of Niaspan in Patients with Type 2 Diabetes

Study Objective. To determine the effect of Niaspan—a niacin preparation with both immediate‐ and extended‐release characteristics—on lipid and glycemic control in patients with type 2 diabetes.

Drug-Induced Thyrotoxic Periodic Paralysis

Objective: To report a case of iodine-induced (Jod–Basedow) hyperthyroidism leading to thyrotoxic periodic paralysis (TPP). Case Summary: A 64-year-old white male, one day status-post-cardiac catheterization, presented to the local emergency department with profound weakness of his extremities and an inability to stand on his own. Pertinent laboratory test results included a potassium level of 3.0 mEq/L Treatments of oral and intravenous potassium supplementation resulted in his complete recovery. Two days later he was diagnosed with hyperthyroidism and subsequently treated with nadolol 40 mg daily and methimazole 20 mg daily. At time of writing, the patient remained euthyroid, receiving no antithyroid medications. There had been no further reports of paralysis in the 6 years since his original presentation. The Naranjo probability scale indicated a probable relationship between the patients episode of TPP and his exposure to the iodinated contrast dye. Discussion: TPP is an uncommon manifestation in white patients with hyperthyroidism. Iodine-induced TPP is even more rare, with only 2 such cases reported as of November 2, 2005. In this case, Jod–Basedow hyperthyroidism was induced by the iodine-containing dye that the patient received during cardiac catheterization. Soon after the dye was administered, he developed TPP. Conclusions: Clinicians should be aware not only of potential causes of drug-induced thyroid disease, but also of the potential for drug-induced hyperthyroidism leading to TPP. The diagnosis of TPP should be considered in patients presenting with acute onset of extremity weakness or paralysis and hypokalemia. Quick diagnosis and prompt treatment of TPP can prevent life-threatening complications of this treatable and curable disorder.

Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes

ABSTRACT Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia. use of glucose-lowering therapies with complementary activities that address multiple facets of the disease may improve long-term outcomes for patients with t2d. two recent drug classes developed for use in t2d, glucagon-like peptide-1 receptor agonists (glp-1ras) and sodium glucose cotransporter 2 (sglt2) inhibitors, have been shown in clinical trials to have beneficial effects on glycemic control, body weight, cardiovascular risk factors, and (for liraglutide, semaglutide, and empagliflozin) cardiovascular outcomes, while having an acceptable safety profile. between them, these drug classes directly or indirectly affect many of the organs and tissues involved in the pathogenesis of t2d, and their beneficial effects on glycemic- and cardiovascular-related parameters are likely to be complementary and potentially additive. in the largest clinical trial of a glp-1ra and an sglt2 inhibitor in combination (duration-8), patients with t2d (n = 685) who received exenatide plus dapagliflozin added to their treatment regimen for 28 weeks had significantly greater reductions from baseline in glycated hemoglobin, body weight, and systolic blood pressure compared with patients who received either drug as monotherapy. this review summarizes the complementary aspects of these drug classes and presents the available data among patients receiving dual therapy with a glp-1ra and an sglt2 inhibitor.

Accuracy and Precision of Four Value-Added Blood Glucose Meters: the Abbott Optium, the DDI Prodigy, the HDI True Track, and the HypoGuard Assure Pro

PURPOSE This study compared the accuracy and precision of four value-added glucose meters. METHODS Finger stick glucose measurements in diabetes patients were performed using the Abbott Diabetes Care (Alameda, CA) Optium, Diagnostic Devices, Inc. (Miami, FL) DDI Prodigy, Home Diagnostics, Inc. (Fort Lauderdale, FL) HDI True Track Smart System, and Arkray, USA (Minneapolis, MN) HypoGuard Assure Pro. Finger glucose measurements were compared with laboratory reference results. Accuracy was assessed by a Clarke error grid analysis (EGA), a Parkes EGA, and within 5%, 10%, 15%, and 20% of the laboratory value criteria (chi2 analysis). Meter precision was determined by calculating absolute mean differences in glucose values between duplicate samples (Kruskal-Wallis test). RESULTS Finger sticks were obtained from 125 diabetes patients, of which 90.4% were Caucasian, 51.2% were female, 83.2% had type 2 diabetes, and average age of 59 years (SD 14 years). Mean venipuncture blood glucose was 151 mg/dL (SD +/-65 mg/dL; range, 58-474 mg/dL). Clinical accuracy by Clarke EGA was demonstrated in 94% of Optium, 82% of Prodigy, 61% of True Track, and 77% of the Assure Pro samples (P < 0.05 for Optium and True Track compared to all others). By Parkes EGA, the True Track was significantly less accurate than the other meters. Within 5% accuracy was achieved in 34%, 24%, 29%, and 13%, respectively (P < 0.05 for Optium, Prodigy, and Assure Pro compared to True Track). Within 10% accuracy was significantly greater for the Optium, Prodigy, and Assure Pro compared to True Track. Significantly more Optium results demonstrated within 15% and 20% accuracy compared to the other meter systems. The HDI True Track was significantly less precise than the other meter systems. CONCLUSIONS The Abbott Optium was significantly more accurate than the other meter systems, whereas the HDI True Track was significantly less accurate and less precise compared to the other meter systems.

Rapid onset of severe retinopathy, cataracts and neuropathy in young patients with diabetes mellitus

It is rare for young diabetic patients to develop severe complications in the first years of their disease. We describe three patients, aged 14–23 years who developed cataracts and severe retinopathy within one to five years of diagnosis of diabetes. During the same period, one patient developed peripheral neuropathy and a second severe autonomic neuropathy. Rapid development of chronic complications in these patients raises the possibility that there may be a subset of patients with unusual susceptibility to complications. We re‐emphasize the need for vigilant monitoring for complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual complaints should be evaluated carefully for evidence of treatable eye disease.