PMID- 29508509 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20181217 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 20 IP - 7 DP - 2018 Jul TI - Safety of intranasal human insulin: A review. PG - 1563-1577 LID - 10.1111/dom.13279 [doi] AB - AIMS: To conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays. MATERIAL AND METHODS: An electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were extracted. RESULTS: A total of 38 studies in 1092 individuals receiving acute human intranasal insulin treatment and 18 studies in 832 individuals receiving human intranasal insulin treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other AEs were less commonly reported. There were no reports of participants being excluded as a result of AEs. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days. CONCLUSIONS: Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ensure the long-term safety of this method of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Schmid, Vera AU - Schmid V AUID- ORCID: 0000-0002-0413-7122 AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. AD - Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tubingen, Tubingen, Germany. FAU - Kullmann, Stephanie AU - Kullmann S AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. FAU - Gfrorer, Wieland AU - Gfrorer W AD - University Pharmacy, University Hospital, Tubingen, Germany. FAU - Hund, Verena AU - Hund V AD - University Pharmacy, University Hospital, Tubingen, Germany. FAU - Hallschmid, Manfred AU - Hallschmid M AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. AD - Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls University Tubingen, Tubingen, Germany. FAU - Lipp, Hans-Peter AU - Lipp HP AD - University Pharmacy, University Hospital, Tubingen, Germany. FAU - Haring, Hans-Ulrich AU - Haring HU AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. AD - Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tubingen, Tubingen, Germany. FAU - Preissl, Hubert AU - Preissl H AUID- ORCID: 0000-0002-8859-4661 AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. AD - Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tubingen, Tubingen, Germany. AD - Institute for Diabetes and Obesity, Helmholtz Diabetes Centre at Helmholtz Zentrum Munchen, German Research Centre for Environmental Health (GmbH), Neuherberg, Germany. AD - Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tubingen, Tubingen, Germany. FAU - Fritsche, Andreas AU - Fritsche A AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. AD - Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tubingen, Tubingen, Germany. FAU - Heni, Martin AU - Heni M AUID- ORCID: 0000-0002-8462-3832 AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center, Munich, at the University of Tubingen, Tubingen, Germany. AD - German Centre for Diabetes Research (DZD e.V.), Tubingen, Germany. AD - Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tubingen, Tubingen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20180406 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Aerosols) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin, Regular, Human) RN - 0 (Recombinant Proteins) SB - IM MH - Administration, Intranasal MH - Aerosols MH - Diabetes Mellitus, Type 1/blood/*drug therapy MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Compounding MH - Drug Stability MH - Humans MH - Hyperglycemia/prevention & control MH - Hypoglycemia/chemically induced/prevention & control MH - Hypoglycemic Agents/*administration & dosage/adverse effects/chemistry/therapeutic use MH - Insulin, Regular, Human/*administration & dosage/adverse effects/chemistry/therapeutic use MH - Protein Stability MH - Recombinant Proteins/*administration & dosage/adverse effects/chemistry/therapeutic use OTO - NOTNLM OT - database research OT - insulin resistance OT - obesity therapy EDAT- 2018/03/07 06:00 MHDA- 2018/12/18 06:00 CRDT- 2018/03/07 06:00 PHST- 2018/01/29 00:00 [received] PHST- 2018/02/26 00:00 [revised] PHST- 2018/02/28 00:00 [accepted] PHST- 2018/03/07 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] PHST- 2018/03/07 06:00 [entrez] AID - 10.1111/dom.13279 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Jul;20(7):1563-1577. doi: 10.1111/dom.13279. Epub 2018 Apr 6.