PMID- 29116540
OWN - NLM
STAT- MEDLINE
DCOM- 20181025
LR  - 20181113
IS  - 1559-0100 (Electronic)
IS  - 1355-008X (Print)
IS  - 1355-008X (Linking)
VI  - 60
IP  - 1
DP  - 2018 Apr
TI  - Long-term safety of long-acting octreotide in patients with diabetic retinopathy: 
      results of pooled data from 2 randomized, double-blind, placebo-controlled phase 
      3 studies.
PG  - 65-72
LID - 10.1007/s12020-017-1448-5 [doi]
AB  - PURPOSE: Octreotide (OCT) has been successfully used for treatment of acromegaly 
      and neuroendocrine tumors for more than 30 years. However, long-term safety of 
      OCT has not been documented in placebo-controlled setting. This present analysis 
      pooled safety data from two similarly-designed, randomized, and 
      placebo-controlled studies to evaluate long-term safety of long-acting OCT (20, 
      30 mg); targeted post-hoc analyzes focused on cardiac, hepatic, and renal safety. 
      METHODS: Two studies (NCT00131144, NCT001308450) were conducted in patients with 
      diabetic retinopathy (OCT20 = 191, OCT30 = 348, placebo = 347). In this analysis, 
      patients were stratified based on baseline glomerular filtration rate. Hepatic, 
      cardiac, and renal adverse events (AEs) were identified by standardized MedDRA 
      queries. RESULTS: Median duration of exposure was >3.5 years. Most common AEs 
      reported with OCT were diarrhea, cholelithiasis, hypoglycemia, nasopharyngitis, 
      and hypertension. Incidence of cardiac events (QT prolongation and arrhythmia) 
      with OCT20 and OCT30 were comparable to placebo (OCT20, RR = 1.11 [95% CI, 
      0.61-2.03]; OCT30, RR = 1.09 [95% CI, 0.70-1.68]). For ECG findings, changes in 
      QTcF were similar in treatment groups, and outliers did not exceed 480 ms. 
      Incidence of cardiac ischemia was lower with OCT than placebo (OCT20 = 12.6%, 
      OCT30 = 10.6%, placebo = 15.3%). Incidence of liver-related AEs was higher with 
      OCT30 than placebo (RR = 2.04 [95% CI, 1.28-3.26]); incidences were comparable 
      with OCT20 and placebo (RR = 1.50 [95% CI, 0.69-3.25]). Overall incidences of 
      renal AEs were comparable between treatment groups (OCT20 = 5.8%; OCT30 = 6.3%; 
      placebo = 7.2%). Drug-related SAEs were reported more frequently with OCT 
      (OCT20 = 7.9%; OCT30 = 10.1%; placebo = 3.5%); predominantly gallbladder-related, 
      GI-related, and hypoglycemia. CONCLUSIONS: The results from these long-term 
      placebo-controlled studies confirm the established safety profile of long-acting 
      OCT, in particular low risk of cardiac, hepatic and renal toxicity in a high-risk 
      population.
FAU - Pivonello, Rosario
AU  - Pivonello R
AD  - Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, 
      Universita Federico II di Napoli, Naples, Italy. rosario.pivonello@unina.it.
FAU - Muscogiuri, Giovanna
AU  - Muscogiuri G
AD  - Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, 
      Universita Federico II di Napoli, Naples, Italy.
FAU - Holder, Geoffrey
AU  - Holder G
AD  - Novartis AG, Basel, Switzerland.
FAU - Paul, Michaela
AU  - Paul M
AD  - Novartis AG, Basel, Switzerland.
FAU - Sarp, Severine
AU  - Sarp S
AD  - Novartis AG, Basel, Switzerland.
FAU - Lesogor, Anastasia
AU  - Lesogor A
AD  - Novartis AG, Basel, Switzerland.
FAU - Jordaan, Pierre
AU  - Jordaan P
AD  - Novartis AG, Basel, Switzerland.
FAU - Eisinger, Johannes
AU  - Eisinger J
AD  - Novartis AG, Basel, Switzerland.
FAU - Colao, Annamaria
AU  - Colao A
AD  - Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, 
      Universita Federico II di Napoli, Naples, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT00131144
SI  - ClinicalTrials.gov/NCT01308450
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20171107
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - RWM8CCW8GP (Octreotide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cholelithiasis/*chemically induced
MH  - Diabetic Retinopathy/*drug therapy
MH  - Diarrhea/*chemically induced
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypertension/*chemically induced
MH  - Hypoglycemia/*chemically induced
MH  - Male
MH  - Middle Aged
MH  - Octreotide/*adverse effects/therapeutic use
PMC - PMC5845597
OTO - NOTNLM
OT  - Cardiac function
OT  - Diabetic retinopathy
OT  - Hepatic function
OT  - Long-term safety
OT  - Octreotide
OT  - Renal function
COIS- G.H., M.P., S.S., A.L., P.J., and J.E. are employees of Novartis. R.P. has been 
      Principal investigator of research studies from Novartis, has received research 
      grants from Novartis, Pfizer, Viropharma and IBSA, has been occasional consultant 
      for Novartis, Ipsen, Pfizer, Viropharma, Ferring, and Italfarmaco, has received 
      Fees and Honoraria for presentations from Novartis and Shire. A.C. is a member of 
      the advisory board Novartis Europe and is recipient of unrestricted funds from 
      Ipsen, Novartis, Pfizer, and Serono for research in neuroendocrinology. G.M. 
      declares that she has no competing interests.
EDAT- 2017/11/09 06:00
MHDA- 2018/10/26 06:00
PMCR- 2017/11/07
CRDT- 2017/11/09 06:00
PHST- 2017/08/23 00:00 [received]
PHST- 2017/09/30 00:00 [accepted]
PHST- 2017/11/09 06:00 [pubmed]
PHST- 2018/10/26 06:00 [medline]
PHST- 2017/11/09 06:00 [entrez]
PHST- 2017/11/07 00:00 [pmc-release]
AID - 10.1007/s12020-017-1448-5 [pii]
AID - 1448 [pii]
AID - 10.1007/s12020-017-1448-5 [doi]
PST - ppublish
SO  - Endocrine. 2018 Apr;60(1):65-72. doi: 10.1007/s12020-017-1448-5. Epub 2017 Nov 7.