Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years

<p>Abstract</p> <p>Background</p> <p>The once-weekly (QW) formulation of the glucagon-like peptide-1 receptor agonist exenatide has been demonstrated to improve A1C, fasting plasma glucose (FPG), body weight, serum lipid profiles, and blood pressure in patients with type 2 diabetes through 52 weeks of treatment. In this report, we describe the 2-year results of the open-label, open-ended extension to the DURATION-1 trial of exenatide QW for type 2 diabetes.</p> <p>Methods</p> <p>A 2-stage protocol was used: patients received either exenatide QW (2 mg) or exenatide twice daily for 30 weeks (5 μg for the first 4 weeks and 10 μg thereafter), followed by 1.5 years of treatment with exenatide QW (2 mg), for a total of 2 years (104 weeks) of exenatide treatment. Of the 295 (intent-to-treat [ITT]) patients who entered the trial, 73% (n = 216) completed 2 years of treatment (completer population). Baseline characteristics (mean ± SE) for these patients were: A1C, 8.2 ± 0.1%; FPG, 168.4 ± 43.0 mg/dL; body weight, 101.1 ± 18.7 kg; and diabetes duration, 7 ± 5 years.</p> <p>Results</p> <p>In the completer population, significant improvements (LS mean ± SE [95% CI]) were maintained after 2 years of treatment in A1C (-1.71 ± 0.08% [-1.86 to -1.55%]), FPG (-40.1 ± 2.9 mg/dL [-45.7 to -34.5 mg/dL]), and body weight (-2.61 ± 0.52 kg [-3.64 to -1.58 kg]) compared with baseline. The percentages of patients who achieved an A1C of <7.0% and ≤6.5% at 2 years were 60% and 39%, respectively. A significant reduction in systolic blood pressure (SBP; -3.0 ± 1.0 mmHg [-4.9 to -1.1 mmHg]) was maintained through 2 years of treatment. Serum lipid profiles were also significantly improved, including triglycerides (geometric LS mean change from baseline, -15 ± 2.7% [-21% to -10%]), total cholesterol (-8.6 ± 2.8 mg/dL [-14.0 to -3.1 mg/dL]), and low-density lipoproteins (-4.5 ± 2.2 mg/dL [-8.9 to -0.01 mg/dL]). Changes in A1C, body weight, FPG, SBP, and lipids in the ITT population were similar to those seen in the completer population. Nausea (predominantly mild in intensity) was the most common adverse event, although the frequency and intensity of nausea decreased over time. No severe hypoglycemia was observed.</p> <p>Conclusions</p> <p>Exenatide QW was well tolerated during the 2-year treatment period. This study demonstrated sustained glucose control and weight loss throughout 2 years of treatment with exenatide QW.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00308139">NCT00308139</a></p

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

Paracellular absorption is relatively low in the herbivorous Egyptian spiny-tailed lizard, Uromastyx aegyptia

Extent: 9 p.Absorption of small water-soluble nutrients in vertebrate intestines occurs both by specific, mediated transport and by nonspecific, passive, paracellular transport. Although it is apparent that paracellular absorption represents a significant route for nutrient absorption in many birds and mammals, especially small, flying species, its importance in ectothermic vertebrates has not previously been explored. Therefore, we measured fractional absorption (e) and absorption rate of three paracellular probes (arabinose, L-rhamnose, cellobiose) and of 3-O-methyl D-glucose (absorbed by both mediated and paracellular pathways) by the large herbivorous lizard, Uromastyx aegyptia, to explore the relative importance of paracellular and mediated transport in an ectothermic, terrestrial vertebrate. Fractional absorption of 3-O-methyl D-glucose was high (e = 0.7360.04) and similar to other vertebrates; e of the paracellular probes was relatively low (arabinose e = 0.3160.03, Lrhamnose e = 0.1960.02, and cellobiose e = 0.1460.02), and decreased with molecular mass, a pattern consistent with other vertebrates. Paracellular absorption accounted for approximately 24% of total 3-O-methyl D-glucose uptake, indicating low reliance on this pathway for these herbivorous lizards, a pattern similar to that found in other terrestrial vertebrates, and different from small flying endotherms (both birds and bats).Todd J. McWhorter, Berry Pinshow, William H. Karasov and Christopher R. Trac

Exenatide once weekly: sustained improvement in glycemic control and cardiometabolic measures through 3 years

Leigh MacConell, Richard Pencek, Yan Li, David Maggs, Lisa PorterAmylin Pharmaceuticals, LLC, San Diego, CA, USABackground: Type 2 diabetes mellitus is a progressive metabolic disease necessitating therapies with sustained efficacy and safety over time. Exenatide once weekly (ExQW), an extended-release formulation of the glucagon-like peptide-1 receptor agonist exenatide, has demonstrated improvements in glycemic and cardiometabolic measures from 30 weeks to 2 years of treatment. Here, the efficacy and safety of treatment with ExQW for 3 years are described.Methods: Patients were initially randomized to receive either ExQW (2 mg) or exenatide twice daily for 30 weeks. Following the initial 30 weeks, all patients were treated with ExQW in an open-label extension. Analyses of primary glycemic endpoints, beta-cell function, and cardiometabolic measures were assessed for patients who completed 3 years of ExQW treatment and for the intention-to-treat population. Safety and tolerability analyses were provided for the intention-to-treat population.Results: Sixty-six percent of the intention-to-treat population (n = 295) completed 3 years of treatment (n = 194). At 3 years, a significant reduction in hemoglobin A1c (least squares mean &amp;plusmn; standard error) of -1.6% &amp;plusmn; 0.08% was observed, with 55% and 33% of patients achieving hemoglobin A1c targets of &amp;lt;7% and &amp;le;6.5%, respectively. Consistent with a sustained reduction in hemoglobin A1c, improvements in beta-cell function were also observed. Body weight was significantly reduced by -2.3 &amp;plusmn; 0.6 kg. Reductions in blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglycerides were also observed. Adverse events reported most frequently during both controlled and uncontrolled periods included diarrhea, nausea, and vomiting of mostly mild intensity. The incidence of these adverse events decreased over time. Incidence of minor hypoglycemia was low and no major hypoglycemia was observed.Conclusion: ExQW produced clinically meaningful improvements in glycemic control that were durable through 3 years of treatment. Significant improvements in cardiometabolic measurements were also observed. ExQW was well-tolerated during long-term treatment and no new adverse events were noted.Trial registration: ClinicalTrials.gov NCT00308139.Keywords: diabetes, exenatide, GLP-1 receptor agonist, hyperglycemia, DURATION-