PMID- 33616643
OWN - NLM
STAT- MEDLINE
DCOM- 20211020
LR  - 20220223
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 8
DP  - 2021 Jul 13
TI  - PREVENT: A Randomized, Placebo-controlled Crossover Trial of Avexitide for 
      Treatment of Postbariatric Hypoglycemia.
PG  - e3235-e3248
LID - 10.1210/clinem/dgab103 [doi]
AB  - CONTEXT: Postbariatric hypoglycemia (PBH), characterized by enteroinsular axis 
      overstimulation and hyperinsulinemic hypoglycemia, is a complication of bariatric 
      surgery for which there is no approved therapy. OBJECTIVE: To evaluate efficacy 
      and safety of avexitide [exendin (9-39)], a glucagon-like peptide-1 antagonist, 
      for treatment of PBH. METHODS: A multicenter, Phase 2, randomized, 
      placebo-controlled crossover study (PREVENT). Eighteen female patients with PBH 
      were given placebo for 14 days followed by avexitide 30 mg twice daily and 60 mg 
      once daily, each for 14 days in random order. The main outcome measures were 
      glucose nadir and insulin peak during mixed-meal tolerance testing (MMTT) and 
      hypoglycemic events captured by self-monitoring of blood glucose (SMBG), 
      electronic diary, and blinded continuous glucose monitoring (CGM). RESULTS: 
      Compared with placebo, avexitide 30 mg twice daily and 60 mg once daily raised 
      the glucose nadir by 21% (P = .001) and 26% (P = .0002) and lowered the insulin 
      peak by 23% (P = .029) and 21% (P = .042), corresponding to 50% and 75% fewer 
      participants requiring rescue during MMTT, respectively. Significant reductions 
      in rates of Levels 1 to 3 hypoglycemia were observed, defined, respectively, as 
      SMBG <70 mg/dL, SMBG <54 mg/dL, and a severe event characterized by altered 
      mental and/or physical function requiring assistance. CGM demonstrated reductions 
      in hypoglycemia without induction of clinically relevant hyperglycemia. Avexitide 
      was well tolerated, with no increase in adverse events. CONCLUSION: Avexitide 
      administered for 28 days was well tolerated and resulted in robust and consistent 
      improvements across multiple clinical and metabolic parameters, reinforcing the 
      targeted therapeutic approach and demonstrating durability of effect. Avexitide 
      may represent a first promising treatment for patients with severe PBH.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Craig, Colleen M
AU  - Craig CM
AUID- ORCID: 0000-0003-1308-6440
AD  - Eiger BioPharmaceuticals, Inc., Palo Alto, CA 94306, USA.
FAU - Lawler, Helen Margaret
AU  - Lawler HM
AUID- ORCID: 0000-0003-3451-1856
AD  - Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, 
      University of Colorado School of Medicine, Aurora, CO 80045, USA.
FAU - Lee, Clare Jung Eun
AU  - Lee CJE
AD  - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, 
      Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
FAU - Tan, Marilyn
AU  - Tan M
AUID- ORCID: 0000-0002-6651-4691
AD  - Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, 
      Stanford University School of Medicine, Stanford, CA 94305, USA.
FAU - Davis, Dawn Belt
AU  - Davis DB
AUID- ORCID: 0000-0002-0239-4715
AD  - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, 
      University of Wisconsin, Madison, WI 53705, USA.
FAU - Tong, Jenny
AU  - Tong J
AUID- ORCID: 0000-0002-5614-3671
AD  - Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, 
      Duke University School of Medicine, Durham, NC 27710, USA.
FAU - Glodowski, Michele
AU  - Glodowski M
AUID- ORCID: 0000-0001-5467-3882
AD  - Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, 
      University of Colorado School of Medicine, Aurora, CO 80045, USA.
FAU - Rogowitz, Elisa
AU  - Rogowitz E
AD  - Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, 
      University of Colorado School of Medicine, Aurora, CO 80045, USA.
FAU - Karaman, Rowan
AU  - Karaman R
AUID- ORCID: 0000-0002-6281-3950
AD  - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, 
      University of Wisconsin, Madison, WI 53705, USA.
FAU - McLaughlin, Tracey L
AU  - McLaughlin TL
AUID- ORCID: 0000-0002-4829-8649
AD  - Eiger BioPharmaceuticals, Inc., Palo Alto, CA 94306, USA.
FAU - Porter, Lisa
AU  - Porter L
AD  - Eiger BioPharmaceuticals, Inc., Palo Alto, CA 94306, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03373435
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (Peptide Fragments)
RN  - 5313W10MYT (exendin (9-39))
SB  - IM
CIN - J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3264-e3265. PMID: 33880551
MH  - Adult
MH  - Bariatric Surgery/*adverse effects
MH  - *Blood Glucose
MH  - Cross-Over Studies
MH  - Female
MH  - Humans
MH  - Hypoglycemia/*drug therapy/etiology
MH  - Male
MH  - Middle Aged
MH  - Peptide Fragments/*therapeutic use
MH  - Postoperative Complications/drug therapy/etiology
MH  - Treatment Outcome
PMC - PMC8277203
OTO - NOTNLM
OT  - GLP-1 antagonist
OT  - PBH
OT  - Postbariatric hypoglycemia
OT  - avexitide
OT  - exendin (939)
OT  - hyperinsulinemic hypoglycemia
EDAT- 2021/02/23 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/02/22
CRDT- 2021/02/22 12:14
PHST- 2021/01/06 00:00 [received]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/02/22 12:14 [entrez]
PHST- 2021/02/22 00:00 [pmc-release]
AID - 6146518 [pii]
AID - dgab103 [pii]
AID - 10.1210/clinem/dgab103 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3235-e3248. doi: 
      10.1210/clinem/dgab103.