Pramlintide: A Human Amylin Analogue Reduced Postprandial Plasma Glucose, Insulin, and C-peptide Concentrations in Patients with Type 2 Diabetes

Thompson, R.; Gottlieb, Alan; Organ, K.; Koda, J.E.; Kisicki, James C.; Kolterman, Orville G.

doi:10.1002/(sici)1096-9136(199707)14:7<547::aid-dia390>3.0.co;2-u

Cited by 70 publications

(36 citation statements)

References 3 publications

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“…Previous clinical studies in patients with type 2 diabetes have shown that the addition of pramlintide to mealtime insulin injections reduces postprandial glycemic excursions (13)(14)(15)22,23). This is achieved via effects that are complementary to those of insulin: a correction of postprandial hyperglucagonemia (20) and a slowing of gastric emptying (21).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies in insulin-treated patients with type 2 diabetes showed that mealtime subcutaneous injection of pramlintide, a synthetic, equipotent, and soluble peptide analog of human amylin, reduced postprandial hyperglucagonemia (20), slowed the rate of gastric emptying (21), and consequently, improved postprandial glucose excursions in this patient population (13)(14)(15)22,23).…”

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confidence: 99%

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Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes

Hollander

Levy

Fineman³

et al. 2003

Diabetes Care

277

270

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OBJECTIVE -Mealtime amylin replacement with the human amylin analog pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of pramlintide in this patient population.RESEARCH DESIGN AND METHODS -In a 52-week, double-blind, placebocontrolled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 Ϯ 10 years, diabetes duration 12 Ϯ 7 years, BMI 34.0 Ϯ 7.0 kg/m 2 , HbA 1c 9.1 Ϯ 1.2%, mean Ϯ SD) treated with insulin (alone or in combination with sulfonylureas and/or metformin) were randomized to receive additional preprandial subcutaneous injections of either placebo or pramlintide (60 g TID, 90 g BID, or 120 g BID).RESULTS -Treatment with pramlintide 120 g BID led to a sustained reduction from baseline in HbA 1c (Ϫ0.68 and Ϫ0.62% at weeks 26 and 52, respectively), which was significantly greater than that seen with placebo (P Ͻ 0.05). The proportion of patients achieving an HbA 1c Ͻ8% was approximately twofold greater with pramlintide (120 g BID) than with placebo (46 vs. 28%, P Ͻ 0.05). The glycemic improvement with pramlintide 120 g BID was accompanied by a mean weight loss (Ϫ1.4 kg vs. ϩ0.7 kg with placebo at week 52, P Ͻ 0.05) and occurred without an overall increase in the severe hypoglycemia event rate. The most common adverse event associated with pramlintide use was transient, mild-to-moderate nausea.CONCLUSIONS -Mealtime amylin replacement with pramlintide 120 g BID, as an adjunct to insulin therapy, improves long-term glycemic and weight control in patients with type 2 diabetes. Diabetes Care 26:784 -790, 2003

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes

Hollander

Levy

Fineman³

et al. 2003

Diabetes Care

277

270

View full text Add to dashboard Cite

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“…Pramlintide (Amylin Pharmaceuticals, San Diego, CA) is a synthetic amylin analog in which the human amylin sequence has been modified to include prolines at residues 25, 28, and 29, as occurs in rat sequence. It is a registered medicine for the treatment of diabetes, and treatment with insulin has proven to improve glucose metabolism in individuals with type 1 diabetes (Thompson et al, 1997b;Weinzimer et al, 2012;Herrmann et al, 2013) and as an independent agent in T2D (Thompson et al, 1997a;Riddle et al, 2007). The mechanism of action includes a slowing of gastric motility (Kong et al, 1997(Kong et al, , 1998) and inhibition of glucagon secretion (Nyholm et al, 1999;Levetan et al, 2003).…”

Section: B Glucagon-like Peptide 1/amylin Coagonismmentioning

confidence: 99%

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

Müller

Clemmensen

Finan

et al. 2018

Pharmacological Reviews

157

126

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“…The first pramlintide study in type 1 diabetic patients explored the effect of an intravenous pramlintide infusion during a Sustacal meal (43) and convincingly demonstrated that the analog was capable of reducing the glycemic response to this challenge, possibly at least partly due to delaying gastric emptying (44). A similar observation was also made in insulin-treated type 2 diabetic patients (45). There is no evidence of an effect of pramlintide administration on insulin sensitivity in either peripheral tissues or the liver in type 1 diabetic patients (46), which reiterates the observations made in healthy individuals using native amylin (34) and which is further supported indirectly using an amylin antagonist (47) in obese type 2 diabetic and nondiabetic individuals.…”

Section: Pramlintide Studies In Diabetic Individualsmentioning

confidence: 87%

Amylin Agonists: A Novel Approach in the Treatment of Diabetes

2004

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Amylin is a peptide hormone that is cosecreted with insulin from the pancreatic ␤-cell and is thus deficient in diabetic people. It inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent. Amylin replacement could therefore possibly improve glycemic control in some people with diabetes. However, human amylin exhibits physicochemical properties predisposing the peptide hormone to aggregate and form amyloid fibers, which may play a part in ␤-cell destruction in type 2 diabetes. This obviously makes it unsuitable for pharmacological use. A stable analog, pramlintide, which has actions and pharmacokinetic and pharmacodynamic properties similar to the native peptide, has been developed. The efficacy and safety of pramlintide administration has been tested in a vast number of clinical trials. Aproximately 5,000 insulin-treated patients have received pramlintide and ϳ250 for >2 years. The aims of this review are to 1) briefly describe actions of amylin as demonstrated in animal and human models and 2) primarily review results from clinical trials with the amylin analog pramlintide. Diabetes 53 (Suppl. 3):

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Pramlintide: A Human Amylin Analogue Reduced Postprandial Plasma Glucose, Insulin, and C-peptide Concentrations in Patients with Type 2 Diabetes

Cited by 70 publications

References 3 publications

Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes

Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

Amylin Agonists: A Novel Approach in the Treatment of Diabetes

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