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Objective: Hypoglycemia (HG) occurs in up to 60% of patients with diabetes mellitus (DM) each year. We assessed a HG alert tool in an electronic health record system, and determined its effect on clinical practice and outcomes. Methods: The tool applied a statistical model, yielding patient-specific information about HG risk. We randomized outpatient primary-care providers (PCPs) to see or not see the alerts. Patients were assigned to study group according to the first PCP seen during four months. We assessed prescriptions, testing, and HG. Variables were compared by multinomial, logistic, or linear model. ClinicalTrials.gov ID: NCT04177147 (registered on 22 November 2019). Results: Patients ( N = 3350) visited 123 intervention PCPs; 3395 patients visited 220 control PCPs. Intervention PCPs were shown 18,645 alerts (mean of 152 per PCP). Patients' mean age was 55 years, with 61% female, 49% black, and 49% Medicaid recipients. Mean baseline A1c and body mass index were similar between groups. During follow-up, the number of A1c and glucose tests, and number of new, refilled, changed, or discontinued insulin prescriptions, were highest for patients with highest risk. Per 100 patients on average, the intervention group had fewer sulfonylurea refills (6 vs. 8; p < .05) and outpatient encounters (470 vs. 502; p < .05), though the change in encounters was not significant. Frequency of HG events was unchanged. Conclusions: Informing PCPs about risk of HG led to fewer sulfonylurea refills and visits. Longer-term studies are needed to assess potential for long-term benefits.

Aims: To assess demographic and clinical characteristics associated with clinical inertia in a real-world cohort of type 2 diabetes mellitus patients not at hemoglobin A1c goal (<7%) on metformin monotherapy. Methods: Adult (≥18 years) type 2 diabetes mellitus patients who received care at Massachusetts General Hospital/Brigham and Women's Hospital and received a new metformin prescription between 1992 and 2010 were included in the analysis. Clinical inertia was defined as two consecutive hemoglobin A1c measures ≥7% ≥3 months apart while remaining on metformin monotherapy (i.e. without add-on therapy). The association between clinical inertia and demographic and clinical characteristics was examined via logistic regression. Results: Of 2848 eligible patients, 43% did not achieve a hemoglobin A1c goal of <7% 3 months after metformin monotherapy initiation. A sub-group of 1533 patients was included in the clinical inertia analysis, of which 36% experienced clinical inertia. Asian race was associated with an increased likelihood of clinical inertia (OR = 2.43; 95% CI = 1.48-3.96), while congestive heart failure had a decreased likelihood (OR = 0.58; 95% CI = 0.32-0.98). Chronic kidney disease and cardiovascular/cerebrovascular disease had weaker associations but were directionally similar to congestive heart failure. Conclusions: Asian patients were at an increased risk of clinical inertia, whereas patients with comorbidities appeared to have their treatment more appropriately intensified. A better understanding of these factors may inform efforts to decrease the likelihood for clinical inertia.

Objective: Hypoglycemia occurs in 20-60% of patients with diabetes mellitus. Identifying at-risk patients can facilitate interventions to lower risk. We sought to develop a hypoglycemia prediction model. Methods: In this retrospective cohort study, urban adults prescribed a diabetes drug between 2004 and 2013 were identified. Demographic and clinical data were extracted from an electronic medical record (EMR). Laboratory tests, diagnostic codes and natural language processing (NLP) identified hypoglycemia. We compared multiple logistic regression, classification and regression trees (CART), and random forest. Models were evaluated on an independent test set or through cross-validation. Results: The 38,780 patients had mean age 57 years; 56% were female, 40% African-American and 39% uninsured. Hypoglycemia occurred in 8128 (539 identified only by NLP). In logistic regression, factors positively associated with hypoglycemia included infection, non-long-acting insulin, dementia and recent hypoglycemia. Negatively associated factors included long-acting insulin plus sulfonylurea, and age 75 or older. The models' area under curve was similar (logistic regression, 89%; CART, 88%; random forest, 90%, with ten-fold cross-validation). Conclusions: NLP improved identification of hypoglycemia. Non-long-acting insulin was an important risk factor. Decreased risk with age may reflect treatment or diminished awareness of hypoglycemia. More complex models did not improve prediction.

Objective: To better manage type 2 diabetes mellitus (T2DM), the tradeoff between improved glycemic control and hypoglycemia should be evaluated. The purpose of this study was to assess the relationship between hypoglycemia and hemoglobin A1c (HbA1c) in a real-world population., Research Design and Methods: Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) was a multi-center, observational study. Patients ≥30 years old using any oral anti-hyperglycemic agent were recruited from seven European and five Asian countries between 2006 and 2007. Hypoglycemia events were collected through patient-reported questionnaires. HbA1c data was collected through chart review. Logistic regression was performed to assess the relationship between hypoglycemia and the most proximate HbA1c levels adjusting for potential confounders (demographics, clinical variables, other medication use, and comorbid conditions)., Results: A total of 4399 patients were recruited and analyzed. Mean age was 60 years, 52% were male, and 75% were on sulfonylureas (S.U.s). Respectively, 37% or 42% of patients reported hypoglycemia in the past 6 (Asia) or 12 months (Europe) before recruitment. Prevalence of hypoglycemia increased significantly (33% to 40%) as HbA1c decreased (p = 0.035). The same trend was also observed among S.U.-treated patients (p < 0.01). After adjusting for confounders, hypoglycemia prevalence was significantly higher for HbA1c <7.0% (odds ratio [O.R.] = 1.66 [95% C.I. 1.21, 2.28]; p = 0.002) vs. HbA1c ≥10.0%., Limitations: Our analyses pooled data from Asia and Europe, which differed in terms of the recall period for ascertaining hypoglycemia symptoms and the timing of latest HbA1c measure., Conclusions: Lower HbA1c level was associated with higher hypoglycemia prevalence among S.U.-treated patients. HbA1c level should be taken into consideration when reporting hypoglycemia prevalence.

Objective: To estimate overall rates of adherence, persistence, and discontinuation for patients with type 2 diabetes mellitus (T2DM) prescribed oral antihyperglycemic agents (OAHAs) by combining results of published studies., Research Design and Methods: A systematic literature review was conducted to identify articles published in English over the last 10 years evaluating the use of OAHAs for the treatment of T2DM. Databases searched included PubMed/MEDLINE, EMBASE, and the Cochrane Library. Seventy studies reporting adherence, persistence or discontinuation were identified by two independent reviewers and 40 reported relevant endpoints for the analysis. Outcomes included: (1) mean adherence defined as the average medication possession ratio (MPR); (2) proportion of adherent patients (MPR ≥ 80%); (3) discontinuation; and (4) persistence. Adherence and persistence were reported in observational studies only. Discontinuation was examined separately in randomized controlled trials (RCTs) and observational studies. Meta-analyses were conducted using both fixed and random effects models. When meta-analysis was not appropriate for a given outcome, descriptive statistics were provided., Results: The pooled mean MPR (95% confidence interval [CI]) was 75.3% (68.8%-81.7%; n = 13) and the proportion of adherent patients (95% CI) was 67.9% (59.6%-76.3%; n = 12). The discontinuation rate (95% CI) in RCTs was 31.8% (17.0%-46.7%; n = 7). Persistence and discontinuation were not assessed via meta-analysis for observational studies due to the limited number of available studies and differences in outcome definitions. In these studies, persistence estimates ranged from 41.0% to 81.1%, with a mean (95% CI) of 56.2% (46.1%-66.3%; n = 6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% CI) of 31.4% (17.6%-45.3%; n = 6)., Limitations: Limitations include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity., Conclusion: The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

Objective: To assess the time from the first observed diagnosis of type 2 diabetes (T2DM) to initiation of an oral antihyperglycemic agent (OAHA) and statin., Methods: In a retrospective US cohort study using the GE electronic medical record database, patients ≥18 years were included if they had a T2DM diagnosis between January 1, 2004 and December 31, 2005 (index period), had a last pre-index HbA1c value ≥7%, and had not received antihyperglycemic agents within one year prior to diagnosis (index date). Patients were eligible for statin therapy but not on a statin within one year before the index date. Patients had medical records for one year prior to (baseline) and two years after (follow up) diagnosis., Results: Of the 2254 eligible patients, 58% were male, mean age was 58 years, mean HbA1c was 8.5%, and mean LDL cholesterol was 115 mg/dL (2.97 mmol/L) at baseline. Additionally, 21% of patients had pre-existing overt cardiovascular disease, 40% had dyslipidemia, 37% were obese, and 11% were smokers. During follow-up, 66.1% and 41.9% of patients initiated an OAHA and a statin, respectively. Among the treated patients, median time from the first observed diabetes diagnosis to therapy initiation was 3 months (interquartile range: 1, 9) for OAHAs and 6 months (2, 13) for statins., Limitations: Treatment initiation with injectable antihyperglycemic agents and/or non-statin lipid-modifying therapies as well as contraindications to OAHAs or statins were not assessed, therefore their impact on our study results cannot be determined. Laboratory measurements were not available for every patient and thus many patients were excluded from the analysis., Conclusion: Treatment initiation with OAHAs and/or statins was suboptimal in patients with T2DM who were treatment eligible and previously untreated with OAHAs and statins. Of those treated, patients initiated treatment with an OAHA more often and earlier than with a statin.

Objective: To assess the impact of hypoglycemia on clinical outcomes among hospitalized, insulin-treated patients., Methods: In a retrospective study, hospitalizations in 2005-2007 were identified from a US inpatient electronic medical records database. All encounters for insulin-treated patients with valid blood glucose measurement were included, except for those with a length of stay <24 hours or >30 days. In an encounter-based analysis, associations between hypoglycemic (glucose ≤70 mg/dL) or severe hypoglycemic (glucose ≤50 mg/dL) episodes and inpatient mortality, ischemic events, neurologic complications, and length of stay were evaluated., Results: Among 107,312 admissions, hypoglycemia occurred in 21,561 (20%) and severe hypoglycemia in 7539 (7%). Inpatient mortality occurred in 6.5% of hospitalizations with hypoglycemia and 3.8% of those without (p < 0.001). Inpatient mortality occurred in 7.6% of hospitalizations with a severe hypoglycemic event. Ischemic events (8.1 vs. 8.0%) and neurologic complications (3.8 vs. 3.7%) were similar in hospitalizations with and without a hypoglycemic event, respectively. In multivariate logistic regression analyses adjusting for age, gender, and selected comorbidities, hypoglycemia was associated with a significant increase in inpatient mortality risk (adjusted odds ratio (OR) = 1.66 [95% CI: 1.55, 1.78]). Similar results were observed with severe hypoglycemia (adjusted OR = 1.44 [1.38, 1.52]). Length of stay was increased in hospitalizations with hypoglycemia (median [interquartile range]: 8.2 days [4.9, 13.9] vs. 5.2 days [3.1, 8.3]; p < 0.0001)., Limitations: Due to the nature of the data source, some data of interest were not available, including insulin dose and dose regimen, outpatient medical histories (including diabetes history), pre-hospitalization medications, and cause of death., Conclusions: Hypoglycemia was common among hospitalized patients receiving insulin and, while a direct causal relationship cannot be assumed, was associated with an increased risk of inpatient mortality and increased length of hospital stay. Hypoglycemia is an undesirable event and efforts to minimize in-hospital hypoglycemic events are warranted across the spectrum of hospitalized patients.

Objective: To compare the incidence of symptomatic hypoglycemia between sitagliptin and sulfonylurea in Muslim patients with type 2 diabetes who fasted during Ramadan., Methods: In a multicenter, pragmatic, randomized study, patients with type 2 diabetes were recruited from clinical centers in India (n = 765) and Malaysia (n = 105). Eligible patients (age ≥ 18 yrs) expressed their intention to daytime fast during Ramadan, were treated with a stable dose of sulfonylurea with or without metformin for ≥3 months prior to screening visit, and had an HbA(1c) ≤ 10%. Patients were randomized in a 1:1 ratio to either switch to sitagliptin 100 mg q.d. or remain on their pre-study sulfonylurea. Daily diary cards were completed to document information on hypoglycemic symptoms and complications. The primary endpoint was the overall incidence of symptomatic hypoglycemia during Ramadan., Results: Of the 870 patients randomized, 848 (n = 421 for sitagliptin and 427 for sulfonylurea) returned ≥1 completed diary card and were included in the analysis. The proportion of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan was lower with sitagliptin (3.8%) compared to sulfonylurea (7.3%). The risk of symptomatic hypoglycemia was significantly lower with sitagliptin (risk ratio [95% CI] = 0.52 [0.29, 0.94]; p = 0.028). By country, the proportions of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan were 4.1% vs. 7.7% in India and 1.9% vs. 3.8% in Malaysia for sitagliptin and sulfonylurea, respectively. No patient discontinued treatment due to a hypoglycemic event. One patient on sitagliptin and seven on sulfonylurea had an event that required non-medical assistance. No events required medical assistance. Both treatments were generally well tolerated., Limitations: Symptomatic hypoglycemic events did not require a confirmatory blood glucose measurement, which may have overestimated hypoglycemic events. Measures of glycemic control and body weight were not assessed., Conclusion: Switching antihyperglycemic treatment to sitagliptin from a sulfonylurea reduced the risk of symptomatic hypoglycemia by approximately 50% for Muslim patients with type 2 diabetes who fasted during Ramadan., Clinical Trial Registration: Clinicaltrials.gov: NCT01340768.

Objectives: To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA(1c)) and medication adherence., Methods: A systematic literature review and meta-analysis were performed to compare the HbA(1c) response and medication adherence between the two drug regimens. Selected articles were limited to studies that compared equivalent drug components within FDC and CDT. Searches used PubMed, Embase, Web of Knowledge, and Cochrane databases. The search results were independently screened and reviewed by two authors (SH, KI). Of the 1246 identified abstracts, 152 articles were reviewed, and ten met the inclusion criteria. Results were extracted and pooled in a meta-analysis, using a random-effects model. Cohort comparisons were described as mean differences (MDs) with 95% confidence intervals (CIs)., Results: The ten articles that met the inclusion criteria had a total study size of 70,573 patients. Four articles reported HbA(1c) results, which had a total of five cohort comparisons of FDC and CDT use. The meta-analysis revealed a significantly greater HbA(1c) reduction with FDC (MD = -0.53% [95% CI: -0.78, -0.28]; p < 0.0001). Eight studies evaluated medication adherence (measured as medication possession ratio [MPR]). Of the eight studies reporting MPR results, a total of 12 cohort comparisons were made and were further divided into three subgroups based on comparison types. Five comparisons described MPR for FDC versus CDT cohorts, with significantly higher MPR with FDC (MD = 8.6% [95% CI: 1.6, 15.6]; p = 0.0162]). Four comparisons examined patients who switched from monotherapy to FDC or CDT, with higher MPR for patients who switched to FDC (MD = 7.7% [95% CI: 5.7, 9.6]; p < 0.0001). Three comparisons described results for patients who switched from CDT to FDC or stayed on CDT, with higher MPR for patients who switched to FDC (MD = 5.0% [95% CI: 3.1, 6.8]; p < 0.0001)., Limitations: A limited number of published studies were available for this meta-analysis and all of those included were observational studies. There was heterogeneity between studies in the statistical methods used to control for confounding variables and differing population characteristics., Conclusions: In a meta-analysis, use of FDCs with antihyperglycemic agents was associated with lower HbA(1c) and higher MPR values compared to CDT use in patients with type 2 diabetes.

Objectives: To determine the incidence of hypoglycaemia during Ramadan in Muslim subjects with type 2 diabetes treated with a sulphonylurea., Methods: In an observational study, eligible subjects were Muslims with type 2 diabetes (age ≥18 years) who were treated with glimepiride, gliclazide, or glibenclamide with or without metformin and who expressed their intention to fast during Ramadan in 2009. Subjects were recruited by clinicians in India, Malaysia, Israel, the United Arab Emirates (UAE), and Saudi Arabia. Each day during Ramadan, patients completed diary cards, which collected information regarding hypoglycaemic symptoms and complications, time from last meal and from last medication, self-monitored blood glucose measurements, and need for assistance. The overall incidence of symptomatic hypoglycaemia recorded during Ramadan was the primary endpoint of interest., Results: Of the enrolled subjects (N = 1397), 1378 returned their diary cards at study end and were included in the analysis. Overall, 89% of subjects who expressed their intention to fast prior to Ramadan reported that they observed the fast during Ramadan. A total of 271 subjects (19.7%) experienced one or more symptomatic hypoglycaemic events during Ramadan, with incidences of 25.6%, 16.8%, and 14.0% observed in subjects treated with glibenclamide, glimepiride, and gliclazide, respectively. By country, the highest incidence of hypoglycaemia was reported by subjects from Israel (40%) followed by those from Malaysia (24%), the UAE (18%), India (13%), and Saudi Arabia (10%). The overall incidence of severe hypoglycaemic events (i.e., events requiring medical or non-medical assistance) was 6.7%, with the highest incidence occurring in the glibenclamide group., Limitations: This was an observational study and as such subjects were not randomised to treatments. While baseline measures appeared comparable, it is possible that differences in measured and unmeasured patient characteristics (e.g., measures of glycaemic control) could partially explain these results. Lastly, no inferential testing was performed on the comparisons between sulphonylurea types and/or countries., Conclusions: In this five-country observational study, nearly 20% of sulphonylurea-treated Muslim subjects with type 2 diabetes experienced symptomatic hypoglycaemia while fasting during Ramadan, with variations across sulphonylureas and countries.

Objectives: To estimate the proportion of patients with type 2 diabetes who were eligible for statin treatment per American Diabetes Association (ADA) recommendations and the proportion who were actually prescribed a statin in US clinical practice. Factors associated with receiving a statin prescription were also determined., Methods: Patients ≥ 25 years diagnosed with type 2 diabetes or had received prescriptions for antihyperglycemic agents between 7/2006 and 6/2008 were identified within a large electronic medical record database. Eligibility for statin therapy was determined according to 2008 ADA recommendations. Statin use was assessed based on prescription records during a 12-month follow-up period. An adjusted logistic regression analysis was performed to estimate the likelihood of statin use in relation to selected baseline characteristics., Results: Of the 125,464 patients identified, 98.5% were eligible for statin therapy. Only 62.9% received a statin prescription during follow-up period. In an adjusted logistic regression, factors associated with increased likelihood of statin use were older age, male gender, smoking, history of cardiovascular conditions, and receiving an antihyperglycemic, antihypertensive, or anticoagulant prescription at baseline (all p < 0.05)., Limitations: Of the patients who did not receive statin during follow-up, 13% of them were previously on a statin during the baseline period. The reasons for discontinuing therapy are not known. It cannot be excluded that some of these patients were intolerant or had contraindications to statin. The data on prescription dispensing and compliance were not recorded., Conclusions: Nearly all patients with type 2 diabetes were eligible for statin therapy, but less than two-thirds received statin therapy in US clinical practice. Efforts to minimize this gap are warranted.

Aims: This study examined the relationship of baseline characteristics and medication use in patients with type 2 diabetes who were prescribed sitagliptin versus other oral antihyperglycemic agents in clinical practice settings in the United States., Methods: The General Electric Healthcare's Clinical Data Services electronic medical record (EMR) database, covering 12 million US patients of all ages from 49 states, was used to identify patients with type 2 diabetes, aged >or=30 years, who received their first sitagliptin, metformin, sulfonylurea, or thiazolidinedione prescription between October 2006 and June 2008 (index period) as part of new mono-, dual, or triple therapy regimens. Patient demographics, diagnoses, prescriptions, and laboratory results were extracted for the 12-month period (baseline) prior to the index date (i.e., date of first prescription). Data were stratified by mono-, dual, or triple therapy and compared between sitagliptin regimens and non-sitagliptin regimens with other oral agents (metformin, sulfonylureas, or thiazolidinediones). Adjusted logistic regression analyses were used to estimate odds ratios (OR) associated with prescribing sitagliptin versus other oral monotherapy in relation to patient baseline characteristics., Results: Among 41,836 patients new to oral monotherapy, 876 (2.1%) received sitagliptin. Compared to patients initiating non-sitagliptin monotherapy, patients on sitagliptin monotherapy were older (64 vs. 60 years) and had lower body mass index (33 kg/m(2) vs. 34 kg/m(2)), higher serum creatinine (1.2 vs. 1.0 mg/dL), higher prevalence of chronic renal disease (7.2% vs. 1.9%), greater use of lipid-lowering agents (42% vs. 38%), and higher prevalence of cardiovascular conditions (CVD: 12.7% vs. 8.3%) and microvascular complications (MVD: 13.4% vs. 5.8%) (all p < 0.05). Of 22,683 patients new to dual therapy, 1885 (8.3%) were on sitagliptin regimens. Relative to patients on non-sitagliptin dual therapy regimens, patients prescribed sitagliptin as part of dual therapy regimens were older and had higher serum creatinine, higher prevalence of CVD, MVD, or chronic renal disease, and greater use of lipid-lowering and antihypertensive agents (all p < 0.05). Among 9967 patients new to triple therapy, 2828 (28.4%) were on triple therapy regimens with sitagliptin. Relative to patients on non-sitagliptin triple therapy regimens, patients on sitagliptin as part of triple therapy regimens were older, and had higher serum creatinine and greater use of antihypertensive or lipid-lowering agents (all p < 0.05). Adjusted logistic regression showed that significant predictors of being prescribed sitagliptin monotherapy were older age (OR 1.01, 95% CI 1.00, 1.02), higher HbA(1c) level (OR 1.10, 95% CI 1.04, 1.17), higher serum creatinine level (OR 1.22, 95% CI 1.08, 1.39), presence of MVD (OR 1.50, 95% CI 1.08, 2.09), and presence of chronic renal disease (OR 2.22, 95% CI 1.41, 3.49)., Limitations: Diabetes care delivered by non-participating physicians is not captured in the GE CDS EMR database and, therefore, the prevalence of the diseases identified based on ICD-9 diagnosis/procedure and CPT codes provided in the Appendix may be underestimated. Duration of diabetes was not consistently recorded and some measures were not available., Conclusion: Patients with type 2 diabetes who were prescribed sitagliptin regimens in clinical practice were older and more likely to have pre-existing co-morbid conditions compared to patients receiving non-sitagliptin regimens with other common oral antihyperglycemic agents. These findings have important implications for observational studies in that estimated clinical and health outcome measures may be biased due to channeling of patients to different therapies based on different baseline characteristics.

Background: Concomitant allergic rhinitis (AR) adds to the symptomatic burden of asthma., Scope: To determine the proportion of adults with concomitant asthma and AR whose AR is diagnosed and/or treated, data were derived from a cross-sectional, stratified, random sample of 26,468 adults from France, Germany and the UK, participants in the 2004 web-based National Health and Wellness Survey. Patients were drawn from the database if they reported (1) experiencing asthma in the prior 12 months, (2) a physician diagnosis of asthma, and (3) ever experiencing 'nasal allergies/hay fever' (physician diagnosed or self-reported symptoms)., Findings: Of 1139 patients with asthma who reported AR, 203 (18%) did not have a diagnosis of AR. Of these, 86 (42%) pursued over-the-counter self-treatment for AR, and 117 (58%) remained untreated. Of 936 patients who reported diagnosed AR, 471 (50%) received AR prescriptions, 200 (21%) pursued over-the-counter self-treatment, and 265 (28%) remained untreated. Overall, 34% of patients with asthma and diagnosed or self-reported AR were not treated for AR. There were no significant differences in QoL over the prior 4 weeks, nor healthcare resource use over the prior 6 months between patients treated and those not treated for AR., Conclusion: Based on self-reported data, despite global treatment guidelines recommending evaluation and treatment of AR among patients with asthma, AR was not diagnosed for 1 in 5 patients, and AR was not treated for 1 in 3 patients with asthma.

Objective: The adequate attainment and maintenance of good hemoglobin A1c control in diabetes are major challenges. Although insulin use as the mainstay of diabetes treatment has resulted in favorable treatment outcomes, poor adherence/compliance occurs due to factors such as fear of insulin or fear of injection. This study was undertaken to conduct a systematic review of the impact of fear of insulin/injection on the treatment outcomes of diabetes patients., Methods: A structured search of EMBASE, Ovid MEDLINE, PubMed, and PsycINFO for the years 1990-2008 was conducted to identify published English-language articles addressing fear of insulin or fear of injection in diabetes. The following key words and their combinations were used in the search: diabetes, insulin, injection, fear, phobia, and psychological insulin resistance. Google Scholar website was used to search for any additional references. Manual searches on the references of retrieved articles were also performed to find additional studies., Results: Six studies were selected for in depth assessment. The treatment outcomes included hemoglobin A1c in two studies, complications of diabetes in two studies, general health and psychological comorbidities in two studies, and mortality in one study. Although the number of studies was limited, all identified adverse treatment outcomes in diabetes patients with fear of insulin or fear of injection. No studies with outcomes of resource utilizations or costs were identified., Limitations: Most of the studies we reviewed had a cross-sectional design, where the findings primarily presented associations without firm determinations of the impact of fear of insulin/injection on the treatment outcomes of diabetes., Conclusions: Fear of insulin or fear of injection is associated with poor glycemic control, clinical complications, psychological comorbidities, poor general well-being and health status, and increased risk of mortality for diabetes patients.