Progressive Reduction in Body Weight after Treatment with the Amylin Analog Pramlintide in Obese Subjects: A Phase 2, Randomized, Placebo-Controlled, Dose-Escalation Study
Abstract
Context: In previous 1-yr trials, treatment with pramlintide (120 μg), an analog of the β-cell hormone amylin, induced sustained reductions in A1C and body weight in insulin-using subjects with type 2 diabetes. Objective: To assess the potential of pramlintide as an antiobesity agent, we assessed the weight effect, safety, and tolerability of pramlintide in non-insulin-treated obese subjects with and without type 2 diabetes at doses greater than previously studied. Design/Setting: We performed a randomized, double-blind, placebo-controlled, multicenter study. Patients: A total of 204 obese subjects [80/20% female/male, age 48 ± 10 yr, and body mass index 37.8 ± 5.6 kg/m2 (mean ± sd)] participated in the study. Intervention: For 16 wk, without concomitant lifestyle intervention, subjects self-administered pramlintide (nonforced dose escalation ≤ 240 μg) or placebo via sc injection three times a day before meals. Main Outcome Measures: Weight, waist circumference, tolerability, and safety were the main outcome measures. Results: Pramlintide was generally well tolerated, with 88% of subjects able to escalate to the maximum dose of 240 μg. Withdrawal rates were similar between placebo (25%) and pramlintide-treated subjects (29%). Subjects completing 16 wk of pramlintide treatment experienced placebo-corrected reductions in body weight of 3.7 ± 0.5% (3.6 ± 0.6 kg; P < 0.001) and waist circumference (3.6 ± 1.1 cm; P < 0.01). Approximately 31% of pramlintide-treated subjects achieved ≥5% weight loss (vs. 2% placebo; P < 0.001). More pramlintide than placebo-treated subjects reported improvements in appetite control (72% vs. 31%), weight control (63% vs. 24%), and overall well-being (52% vs. 17%). No unexpected safety signals were observed. The most common adverse event reported was mild, transient nausea. Pramlintide-treated subjects not reporting nausea experienced weight loss similar to those who did (3.6 ± 0.5% and 3.9 ± 0.5%, respectively). Conclusion: These results support continued evaluation of pramlintide as a potential treatment for obesity.
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A subsequent study of pramlintide demonstrated an additional mean weight loss of 3.7 kg versus placebo in obese patients without T2DM or with non-insulin-treated T2DM.
“A subsequent study of pramlintide demonstrated an additional mean weight loss of 3.7 kg vs. placebo in obese patients without T2DM or with non-insulin-treated T2DM [89].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [89]
Studies of pramlintide in obese patients without type 2 diabetes demonstrated reductions in BP that were directly associated with weight loss.
“Studies aimed at assessing the weight loss potential of pramlintide in obese patients without type 2 diabetes demonstrated reductions in BP that were directly associated with weight loss.213,214”
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- Authors
- Aronne, L., Fujioka, K., Aroda, V., Chen, K., Halseth, A., Kesty, N. C., Burns, C., Lush, C. W., & Weyer, C.
- Affiliations
- Cornell University (US)
- Scripps Health (US)
- University of California San Diego (US)
- Amylin Pharmaceuticals, Incorporated (K.C., A.H., N.C.K., C.B., C.W.L., C.W.), San Diego, California 92121
- Corresponding author
- Weyer, Christian
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2007-08-01
- Volume
- 92
- Issue
- 8
- Pages
- 2977-2983
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2075691591
- Cited by
- 178
- References
- 29
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 20 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 13 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 10 · 2012: 14
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- pramlintide, amylin analogues, obesity, weight loss, type 2 diabetes, dose escalation, waist circumference, appetite regulation, nausea, drug safety and tolerability, subcutaneous administration, insulin-treated patients, non-insulin-treated patients, glycemic control, HbA1c, self-administration, adverse events, withdrawal rate, body mass index
- MeSH terms
- Adult, Amyloid, Anthropometry, Body Weight, Dose-Response Relationship, Drug, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Middle Aged, Obesity, Surveys and Questionnaires, Treatment Outcome, Anti-Obesity Agents, Islet Amyloid Polypeptide
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