Barriers to insulin therapy remain a critical challenge for individuals with insulin-treated diabetes, contributing to suboptimal clinical outcomes. The Afrezza® inhaled insulin system, with Technosphere® insulin (TI), is a promising alternative to subcutaneous insulin injections, offering a rapid pharmacokinetic profile and ease of use. Clinical studies demonstrate comparable HbA1c reductions, fewer hypoglycemic events, and improved treatment satisfaction with TI compared with rapid-acting insulin analogs. By addressing barriers such as needle aversion, injection-related pain, and variable insulin absorption, TI has the potential to enhance diabetes treatment and quality of life. Individual choice, supported by shared decision-making, is essential for individualized diabetes care, empowering people with diabetes and improving outcomes. Broader adoption requires increased clinician awareness and insurance coverage.
Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2024. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Available from: https://www.cdc.gov/diabetes/php/data-research/index.html [Last accessed: September19, 2025].
HankoskyER, SchapiroD, GunnKB, et al. Gaps Remain for Achieving HbA1c Targets for People with Type 1 or Type 2 Diabetes Using Insulin: Results from NHANES 2009–2020. Diabetes Ther, 2023; 14(6):967–975; doi: 10.1007/s13300-023-01399-0
4.
FerreiraROM, TrevisanT, PasqualottoE, et al.Continuous Glucose Monitoring Systems in Noninsulin-Treated People with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diabetes Technol Ther, 2024; 26(4):252–262; doi: 10.1089/dia.2023.0390
5.
PolonskyWH, HoodKK, LevyCJ, et al.; Omnipod 5 Research Group. How introduction of automated insulin delivery systems may influence psychosocial outcomes in adults with type 1 diabetes: Findings from the first investigation with the Omnipod® 5 System. Diabetes Res Clin Pract, 2022; 190:109998; doi: 10.1016/j.diabres.2022.109998
6.
NakajimaH, OkadaS, MohriT, et al.Dapagliflozin improves treatment satisfaction in overweight patients with type 2 diabetes mellitus: A patient reported outcome study (PRO study). Diabetol Metab Syndr, 2018; 10:11; doi: 10.1186/s13098-018-0313-x
7.
TakaseT, NakamuraA, YamamotoC, et al.Improvement in treatment satisfaction after switching from liraglutide to dulaglutide in patients with type 2 diabetes: A randomized controlled trial. J Diabetes Investig, 2019 May;10(3):699–705; doi: 10.1111/jdi.12906
8.
KarterAJ, SubramanianU, SahaC, et al.Barriers to insulin initiation: The translating research into action for diabetes insulin starts project. Diabetes Care, 2010; 33(4):733–735.
9.
PeyrotM, RubinRR, KrugerDF, TravisLB. Correlates of insulin injection omission. Diabetes Care, 2010; 33(2):240–245.
10.
OleckJ, KassamS, GoldmanJD. Commentary: Why was inhaled insulin a failure in the market? Diabetes Spectr, 2016; 29(3):180–184; doi: 10.2337/diaspect.29.3.180
11.
PeyrotM, RubinRR. Effect of technosphere inhaled insulin on quality of life and treatment satisfaction. Diabetes Technol Ther, 2010; 12(1):49–55; doi: 10.1089/dia.2009.0115
12.
TestaMA, SimonsonDC. Satisfaction and quality of life with premeal inhaled versus injected insulin in adolescents and adults with type 1 diabetes. Diabetes Care, 2007 Jun;30(6):1399–1405; doi: 10.2337/dc06-1497
13.
RosenstockJ, CappelleriJC, BolinderB, GerberRA. Patient satisfaction and glycemic control after 1 year with inhaled insulin (Exubera) in patients with type 1 or type 2 diabetes. Diabetes Care, 2004; 27(6):1318–1323; doi: 10.2337/diacare.27.6.1318
14.
CappelleriJC, CefaluWT, RosenstockJ, et al.Treatment satisfaction in type 2 diabetes: A comparison between an inhaled insulin regimen and a subcutaneous insulin regimen. Clin Ther, 2002; 24(4):552–564; doi: 10.1016/s0149-2918(02)85131-1
15.
PolonskyWH, HenryRR. Poor medication adherence in type 2 diabetes: Recognizing the scope of the problem and its key contributors. Patient Prefer Adherence, 2016; 10:1299–1307.
16.
OsterbergL, BlaschkeT. Adherence to medication. N Engl J Med, 2005; 353(5):487–497; doi: 10.1056/NEJMra050100
17.
DanneTPA, JoubertM, HartvigNV, et al.Association Between Treatment Adherence and Continuous Glucose Monitoring Outcomes in People With Diabetes Using Smart Insulin Pens in a Real-World Setting. Diabetes Care, 2024; 47(6):995–1003; doi: 10.2337/dc23-2176
18.
BrodM, RanaA, BarnettAH. Impact of self-treated hypoglycaemia in type 2 diabetes: A multinational survey in patients and physicians. Curr Med Res Opin, 2012; 28(12):1947–1958.
19.
PeyrotM, BarnettAH, MeneghiniLF, Schumm-DraegerPM. Factors associated with injection omission/non-adherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Obes Metab, 2012; 14(12):1081–1087.
20.
McGovernA, TippuZ, HintonW, et al.Comparison of medication adherence and persistence in type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab, 2018; 20(4):1040–1043; doi: 10.1111/dom.13160
21.
BoonpattharatthitiK, SaensookT, NeelapaijitN, et al.The prevalence of adherence to insulin therapy in patients with diabetes: A systematic review and meta-analysis. Res Social Adm Pharm, 2024; 20(3):255–295; doi: 10.1016/j.sapharm.2023.11.009
22.
NguyenD, LiangX, NguyenST, et al.Association between insulin adherence and hemoglobin A1c: A systematic review and meta-analysis. JMCP, 2024; 30(10):1167–1177; doi: 10.18553/jmcp.2024.30.10.1167
23.
PeyrotM, BarnettAH, MeneghiniLF, Schumm-DraegerPM. Insulin adherence behaviors and barriers in the multinational Global Attitudes of Subjects and Physicians in Insulin Therapy study. Diabet Med, 2012; 29(5):682–689.
24.
LiuC, De RozaJ, OoiCW, et al.Impact of patients’ beliefs about insulin on acceptance and adherence to insulin therapy: A qualitative study in primary care. BMC Prim Care, 2022; 23(1):15; doi: 10.1186/s12875-022-01627-9
25.
MazzottaFA, Lucaccini PaoliL, RizziA, et al.Unmet needs in the treatment of type 1 diabetes: Why is it so difficult to achieve an improvement in metabolic control? Nutr Diabetes, 2024; 14(1):58; doi: 10.1038/s41387-024-00319-w
26.
PeyrotM, RubinRR, KhuntiK. Addressing barriers to initiation of insulin in patients with type 2 diabetes. Prim Care Diabetes, 2010; 4,(Suppl 1):S11–S18.
27.
BaiX, LiuZ, LiZ, YanD. The association between insulin therapy and depression in patients with type 2 diabetes mellitus: A meta-analysis. BMJ Open, 2018; 8(11):e020062; doi: 10.1136/bmjopen-2017-020062
28.
PolonskyWH, FisherL, EarlesJ, et al.Assessing psychosocial distress in diabetes: Development of the diabetes distress scale. Diabetes Care, 2005; 28(3):626–631; doi: 10.2337/diacare.28.3.626
29.
BenroubiM. Fear, guilt feelings and misconceptions: Barriers to effective insulin treatment in type 2 diabetes. Diabetes Res Clin Pract, 2011; 93 (Suppl 1):S97–S99; doi: 10.1016/S0168-8227(11)70021-3
30.
AschnerP, GagliardinoJJ, IlkovaH, et al.High prevalence of depressive symptoms in patients with type 1 and type 2 diabetes in developing countries: Results from the international diabetes management practices study. Diabetes Care, 2021; 44(5):1100–1107; doi: 10.2337/dc20-2003
31.
GonzalezJS, PeyrotM, McCarlLA, et al.Depression and Diabetes Treatment Nonadherence: A Meta-Analysis. Diabetes Care, 2008; 31(12):2398–2403.
32.
LinEH, RutterCM, KatonW, et al.Depression and advanced complications of diabetes: A prospective cohort study. Diabetes Care, 2010; 33(2):264–269; doi: 10.2337/dc09-1068
33.
Wojujutari AjeleK, Sunday IdemudiaE. The role of depression and diabetes distress in glycemic control: A meta-analysis. Diabetes Res Clin Pract, 2025 Mar;221:112014; doi: 10.1016/j.diabres.2025.112014
34.
Gonder-FrederickL, NyerM, ShepardJA, et al.Assessing fear of hypoglycemia in children with Type 1 diabetes and their parents. Diabetes Manag (Lond), 2011; 1(6):627–639.
35.
LiuJ, BisphamJ, FanL, et al.Factors associated with fear of hypoglycaemia among the T1D Exchange Glu population in a cross-sectional online survey. BMJ Open, 2020; 10(9):e038462; doi: 10.1136/bmjopen-2020-038462
36.
ShiL, ShaoH, ZhaoY, ThomasNA. Is hypoglycemia fear independently associated with health-related quality of life? Health Qual Life Outcomes, 2014 Nov 30;12:167; doi: 10.1186/s12955-014-0167-3
37.
PeterME, RiolesN, LiuJ, et al.Prevalence of fear of hypoglycemia in adults with type 1 diabetes using a newly developed screener and clinician’s perspective on its implementation. BMJ Open Diabetes Res Care, 2023 Jul;11(4):e003394; doi: 10.1136/bmjdrc-2023-003394
38.
SakaneN, KotaniK, TsuzakiK, et al.Fear of hypoglycemia and its determinants in insulin-treated patients with type 2 diabetes mellitus. J Diabetes Investig, 2015; 6(5):567–570; doi: 10.1111/jdi.12340
39.
HeiseT, MeneghiniLF. Insulin stacking versus therapeutic accumulation: Understanding the differences. Endocr Pract, 2014; 20(1):75–83; doi: 10.4158/EP13090.RA
40.
HirschIB, KhakpourD, JosephJ, et al.The DERMIS study: Methodologies, results, and implications for the future. J Diabetes Sci Technol, 2024:19322968241298005; doi: 10.1177/19322968241298005
41.
KalusA, ShinoharaMM, WangR, et al.Evaluation of insulin pump infusion sites in type 1 diabetes: The DERMIS study. Diabetes Care, 2023; 46(9):1626–1632; doi: 10.2337/dc23-0426
42.
LiuJ, MillerK, KellyC, et al.289-OR: Automated insulin delivery use among 12,065 T1D exchange registry participants. Diabetes, 2022; 71(Supplement_1):289-OR; doi: 10.2337/db22-289-OR
43.
MKC-TI-171. Trial 171: A phase 3, multicenter, open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of Technosphere® insulin inhalation powder in combination with a basal insulin versus insulin aspart in combination with a basal insulin in subjects with type 1 diabetes mellitus over a 24-week treatment period. Clinical Trials.gov Identifier NCT01445951, 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT01445951?term=NCT01445951&rank=1[Last accessed: March 30, 2017].
44.
BodeBW, McGillJB, LorberDL, et al.; Affinity 1 Study Group. Inhaled Technosphere Insulin Compared With Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial. Diabetes Care, 2015; 38(12):2266–2273.
45.
MKC-TI-102. Efficacy of meal-time AFRESA in combination with a long-acting basal insulin versus twice daily injections of pre-mixed insulin (a mixture of rapid-acting insulin and intermediate-acting insulin) in patients with type 2 diabetes. 2010. Clinical Trials.gov identifier NCT00309244. Available from: https://clinicaltrials.gov/ct2/show/NCT00309244?term=NCT00309244&rank=1 [Last accessed: April8, 2017].
46.
RosenstockJ, FrancoD, KorpachevV, et al.; Affinity 2 Study Group. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. Diabetes Care, 2015; 38(12):2274–2281; doi: 10.2337/dc15-0629
47.
SantosVKJD, PradoMLL, Da SilvaGSN, et al.Technosphere insulin in the treatment of Type 1 diabetes mellitus: A systematic review and meta-analysis. J Diabetes Complications, 2025; 39(9):109108; doi: 10.1016/j.jdiacomp.2025.109108
48.
HirschIB, BeckRW, MarakMC, et al.; INHALE-3 Study Group. A Randomized Trial Comparing Inhaled Insulin Plus Basal Insulin Versus Usual Care in Adults With Type 1 Diabetes. Diabetes Care, 2025; 48(3):353–360; doi: 10.2337/dc24-1832
49.
BeckRW, BaileyRJ, AkturkHK, et al.; INHALE-3 Study Group. A 13-Week Single-Arm Evaluation of Inhaled Technosphere Insulin Plus Insulin Degludec for Adults with Type 1 Diabetes. Diabetes Technol Ther, 2025; 27(3):161–169; doi: 10.1089/dia.2024.0581
50.
GreeneSF, NikulaKJ, PoulinD, et al.Long-Term Nonclinical Pulmonary Safety Assessment of Afrezza, a Novel Insulin Inhalation Powder. Toxicol Pathol, 2021; 49(2):334–348; doi: 10.1177/0192623320960420
51.
GerberRA, CappelleriJC, KouridesIA, GelfandRA. Treatment satisfaction with inhaled insulin in patients with type 1 diabetes: A randomized controlled trial. Diabetes Care, 2001; 24(9):1556–1559; doi: 10.2337/diacare.24.9.1556
52.
KidanemariamM, GranerMA, BosWJW, et al.Patient-clinician collaboration in making care fit: A qualitative analysis of clinical consultations in diabetes care. Patient Educ Couns, 2024 Aug;125:108295; doi: 10.1016/j.pec.2024.108295
53.
WilliamsGC, FreedmanZR, DeciEL. Supporting autonomy to motivate patients with diabetes for glucose control. Diabetes Care, 1998; 21(10):1644–1651; doi: 10.2337/diacare.21.10.1644
54.
Freeman-HildrethY, AronD, ColaPA, et al.Empowering diabetes management: The impact of patient-provider collaboration on type 2 diabetes outcomes through autonomy support and shared decision-making. Patient Educ Couns, 2024; 127:108348; doi: 10.1016/j.pec.2024.108348
55.
American Diabetes Association. 7. Diabetes Technology: Standards of Medical Care in Diabetes—2025. Diabetes Care, 2025(48(Supplement_1):S146–S166; doi: 10.2337/dc25-S007
56.
AkturkHK, Snell-BergeonJK, RewersA, et al.Improved Postprandial Glucose with Inhaled Technosphere Insulin Compared with Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The STAT Study. Diabetes Technol Ther, 2018; 20(10):639–647; doi: 10.1089/dia.2018.0200
