{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:51:23Z","timestamp":1790621483269,"version":"4.1.0"},"reference-count":26,"publisher":"American Diabetes Association","issue":"10","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,10,1]]},"abstract":"<jats:p>OBJECTIVE\u2014To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014This 29-week, double-blind, placebo-controlled study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide was escalated from 15 to 60 \u03bcg\/meal (15-\u03bcg increments) with recommended reductions (30\u201350%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA1c (A1C), postprandial glucose, insulin, weight, and tolerability.<\/jats:p>\n               <jats:p>RESULTS\u2014Baseline A1C was 8.1% for both groups and at week 29 had decreased comparably (pramlintide \u22120.5% [95% CI \u22120.61 to \u22120.33]; placebo \u22120.5% [\u22120.63 to \u22120.35]). Pramlintide treatment significantly reduced postprandial glucose excursions (incremental area under the curve [AUC]0\u20133h: pramlintide \u2212175 \u00b1 40, placebo \u221264 \u00b1 38 mg \u00b7 h\u22121 \u00b7 dl\u22121; P &amp;lt; 0.0005) and weight (pramlintide \u22121.3 \u00b1 0.30, placebo +1.2 \u00b1 0.30 kg; P &amp;lt; 0.0001). At week 29, insulin dose decreased by 28 and 4% in pramlintide- and placebo-treated groups, respectively. Nausea, reported by 63 and 36% of patients in pramlintide and placebo groups (P &amp;lt; 0.01), respectively, was predominately mild to moderate in intensity. Severe hypoglycemia rates were low in both groups (pramlintide 0.57 \u00b1 0.09, placebo 0.30 \u00b1 0.06 event rate\/patient-year; P &amp;lt; 0.05), with increased rates observed in patients remaining at 30 \u03bcg pramlintide.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Pramlintide dose escalation with reduced mealtime insulin was effective during therapy initiation in patients with type 1 diabetes. While both groups experienced equivalent A1C reductions relative to placebo, pramlintide-treated patients experienced reductions in postprandial glucose excursions and weight, not achievable with insulin therapy alone.<\/jats:p>","DOI":"10.2337\/dc06-0042","type":"journal-article","created":{"date-parts":[[2006,9,26]],"date-time":"2006-09-26T19:48:41Z","timestamp":1159300121000},"page":"2189-2195","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":148,"title":["A Double-Blind, Placebo-Controlled Trial Assessing Pramlintide Treatment in the Setting of Intensive Insulin Therapy in Type 1 Diabetes"],"prefix":"10.2337","volume":"29","author":[{"given":"Steve","family":"Edelman","sequence":"first","affiliation":[{"name":"Division of Diabetes\/Metabolism, San Diego VA Medical Center, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Garg","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Frias","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Maggs","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Strobel","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Lutz","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orville","family":"Kolterman","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031215543913800_R1","doi-asserted-by":"crossref","unstructured":"Young AA: Amylin\u2019s physiology and its role in diabetes. Curr Opin Endocrinol Diab\u20084: 282\u2013290, 1997","DOI":"10.1097\/00060793-199708000-00006"},{"key":"2022031215543913800_R2","doi-asserted-by":"crossref","unstructured":"Young AA, Gedulin B, Vine W, Percy A, Rink TJ: Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin. Diabetologia\u200838:642\u2013648, 1995","DOI":"10.1007\/BF00401833"},{"key":"2022031215543913800_R3","doi-asserted-by":"crossref","unstructured":"Gedulin BR, Rink TJ, Young AA: Dose-response for glucagonostatic effect of amylin in rats. Metabolism\u200846:67\u201370, 1997","DOI":"10.1016\/S0026-0495(97)90170-0"},{"key":"2022031215543913800_R4","doi-asserted-by":"crossref","unstructured":"Lutz TA, Mollet A, Rushing PA, Riediger T, Scharrer E: The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema\/nucleus of the solitary tract (AP\/NTS) lesioned rats. Int J Obes Relat Metab Disord\u200825:1005\u20131011, 2001","DOI":"10.1038\/sj.ijo.0801664"},{"key":"2022031215543913800_R5","doi-asserted-by":"crossref","unstructured":"Rushing PA, Lutz TA, Seeley RJ, Woods SC: Amylin and insulin interact to reduce food intake in rats. Horm Metab Res\u200832:62\u201366, 2000","DOI":"10.1055\/s-2007-978590"},{"key":"2022031215543913800_R6","unstructured":"SYMLIN [package insert]. San Diego, CA, Amylin Pharmaceuticals, 2005"},{"key":"2022031215543913800_R7","doi-asserted-by":"crossref","unstructured":"Whitehouse F, Kruger DF, Fineman M, Shen L, Ruggles JA, Maggs DG, Weyer C, Kolterman OG: A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care\u200825:724\u2013730, 2002","DOI":"10.2337\/diacare.25.4.724"},{"key":"2022031215543913800_R8","doi-asserted-by":"crossref","unstructured":"Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG: Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in type 1 diabetes mellitus: a one-year randomized controlled trial. Diabet Med\u200821:1204\u20131212, 2004","DOI":"10.1111\/j.1464-5491.2004.01319.x"},{"key":"2022031215543913800_R9","doi-asserted-by":"crossref","unstructured":"Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Strobel S, Wang Y, Burns C, Lush C, Weyer C, Horowitz M: Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia\u200848:838\u2013848, 2005","DOI":"10.1007\/s00125-005-1732-4"},{"key":"2022031215543913800_R10","doi-asserted-by":"crossref","unstructured":"The DCCT Research Group: Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med\u200890:450\u2013459, 1991","DOI":"10.1016\/0002-9343(91)90605-W"},{"key":"2022031215543913800_R11","doi-asserted-by":"crossref","unstructured":"Phillips KF: Power of the two one-sided tests procedure in bioequivalence. J Pharmacokinet Biopharm\u200818:137\u2013143, 1990","DOI":"10.1007\/BF01063556"},{"key":"2022031215543913800_R12","doi-asserted-by":"crossref","unstructured":"Weyer C, Gottlieb A, Kim DD, Lutz K, Schwartz S, Gutierrez M, Wang Y, Ruggles JA, Kolterman OG, Maggs DG: Pramlintide reduces postprandial glucose excursions when added to regular insulin or insulin lispro in patients with type 1 diabetes: a dose-timing study. Diabetes Care\u200826:3074\u20133079, 2003","DOI":"10.2337\/diacare.26.11.3074"},{"key":"2022031215543913800_R13","doi-asserted-by":"crossref","unstructured":"Monnier L, Lapinski H, Colette C: Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care\u200826:881\u2013885, 2003","DOI":"10.2337\/diacare.26.3.881"},{"key":"2022031215543913800_R14","doi-asserted-by":"crossref","unstructured":"Balkau B, Shipley M, Jarrett RJ, Pyorala K, Pyorala M, Forhan A, Eschwege E: High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men: 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study. Diabetes Care\u200821:360\u2013367, 1998","DOI":"10.2337\/diacare.21.3.360"},{"key":"2022031215543913800_R15","doi-asserted-by":"crossref","unstructured":"de Vegt F, Dekker JM, Ruhe HG, Stehouwer CDA, Nijpels G, Bouter LM, Heine RJ: Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn study. Diabetologia\u200842:926\u2013931, 1999","DOI":"10.1007\/s001250051249"},{"key":"2022031215543913800_R16","doi-asserted-by":"crossref","unstructured":"Home P: Contributions of basal and post-prandial hyperglycaemia to micro- and macrovascular complications in people with type 2 diabetes. Curr Med Res Opin\u200821:989\u2013998, 2005","DOI":"10.1185\/030079905X49662"},{"key":"2022031215543913800_R17","doi-asserted-by":"crossref","unstructured":"Lowe LP, Liu K, Greenland P, Metzger BE, Dyer AR, Stamler J: Diabetes, asymptomatic hyperglycemia, and 22-year mortality in black and white men: the Chicago Heart Association Detection Project in Industry Study. Diabetes Care\u200820:163\u2013169, 1997","DOI":"10.2337\/diacare.20.2.163"},{"key":"2022031215543913800_R18","doi-asserted-by":"crossref","unstructured":"Donahue RP, Abbott RD, Reed DM, Yano K: Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry: Honolulu Heart Program. Diabetes\u200836:689\u2013692, 1987","DOI":"10.2337\/diabetes.36.6.689"},{"key":"2022031215543913800_R19","doi-asserted-by":"crossref","unstructured":"Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, Ziegelasch HJ, Lindner J: Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia\u200839:1577\u20131583, 1996","DOI":"10.1007\/s001250050617"},{"key":"2022031215543913800_R20","doi-asserted-by":"crossref","unstructured":"Hirsch IB, Brownlee M: Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications\u200819:178\u2013181, 2005","DOI":"10.1016\/j.jdiacomp.2004.10.001"},{"key":"2022031215543913800_R21","doi-asserted-by":"crossref","unstructured":"Ceriello A, Motz E: Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol\u200824:816\u2013823, 2004","DOI":"10.1161\/01.ATV.0000122852.22604.78"},{"key":"2022031215543913800_R22","doi-asserted-by":"crossref","unstructured":"The Diabetes Control and Complications Trial Research Group: Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care\u200824:1711\u20131721, 2001","DOI":"10.2337\/diacare.24.10.1711"},{"key":"2022031215543913800_R23","doi-asserted-by":"crossref","unstructured":"Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD: Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. JAMA\u2008280:140\u2013146, 1998","DOI":"10.1001\/jama.280.2.140"},{"key":"2022031215543913800_R24","doi-asserted-by":"crossref","unstructured":"The Diabetes Control and Complications Trial Research Group: Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial. Diabetes Care\u200811:567\u2013573, 1988","DOI":"10.2337\/diacare.11.7.567"},{"key":"2022031215543913800_R25","doi-asserted-by":"crossref","unstructured":"Bryden KS, Neil A, Mayou RA, Peveler RC, Fairburn CG, Dunger DB: Eating habits, body weight and insulin misuse: a longitudinal study of teenagers and young adults with type 1 diabetes. Diabetes Care\u200822:1956\u20131960, 1999","DOI":"10.2337\/diacare.22.12.1956"},{"key":"2022031215543913800_R26","doi-asserted-by":"crossref","unstructured":"Snell-Bergeon JK, Hokanson JE, Jensen L, MacKenzie T, Kinney G, Dabelea D, Eckel RH, Ehrlich J, Garg S, Rewers M: Progression of coronary artery calcification in type 1 diabetes: the importance of glycemic control. Diabetes Care\u200826:2923\u20132928, 2003","DOI":"10.2337\/diacare.26.10.2923"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/29\/10\/2189\/591425\/zdc01006002189.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/29\/10\/2189\/591425\/zdc01006002189.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T16:09:28Z","timestamp":1647101368000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/29\/10\/2189\/23579\/A-Double-Blind-Placebo-Controlled-Trial-Assessing"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,1]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2006,10,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc06-0042","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,1]]}}}