Clinical Scenario:
You are a PA working in a family medicine clinic and you have a patient who has recently been diagnosed with diabetes mellitus. As you are discussing her options, she cuts you off and begins to tell you how at her last PTA meeting other parents have been saying that subcutaneous insulin infusion is the “best way” to manage diabetes.
Search Question:
Among patients with diabetes mellitus does using continuous subcutaneous insulin infusion compared to multiple daily insulin injections lead to better glycemic control and improved quality of life?
PICO Table:
| P | I | C | O |
| Diabetes | Insulin pump | Insulin injections | Improved glycemic control |
| Diabetes mellitus | Continuous subcutaneous insulin | Multiple daily insulin injections | Decreased glucose |
| Type 1 diabetes | Continuous subcutaneous insulin infusion | Insulins and analogues | Decreased A1C |
| Type 2 diabetes | Improved quality of life |
Search Strategy and Databases Used:
Pub Med:
(diabetes)AND (continuous subcutaneous insulin infusion) AND (insulin injections): 1,321 results
- Filters: last 15 years, full text: 338 results
- Filters: last 15 years, full text, RCT, meta-analysis, systematic review: 74 results
diabetes) AND (continuous subcutaneous insulin infusion) AND (insulin injections) AND (glycemic control): 389 results
- Filters: last 15 years, full text: 256 results
- Filters: last 15 years, full text, RCT, meta-analysis, systematic review: 50 results
Cochrane:
Population “diabetes” Intervention “Continuous subcutaneous insulin” Comparison “Insulin injections” Outcome “glycemic control”: 3 results
Trip Medical Database:
Population “diabetes” Intervention “Continuous subcutaneous insulin” Comparison “Insulin injections” Outcome “glycemic control”: 12 results
Explanation: At first, I searched diabetes, continuous subcutaneous insulin infusion, and insulin injections on PubMed and encountered many different articles, this then led to me apply the filter of “within the last 15 years” and free text. After doing this I still encountered 338 different articles and wanted to limit this, so I added another filter of RCT, meta-analysis, and systematic review which brought the results down to 74 results. I also searched diabetes, continuous subcutaneous insulin infusion, insulin injections, and glycemic control on PubMed using the same criteria and ended at a manageable 50 results. When doing my search on Cochrane I put in diabetes for population, continuous subcutaneous insulin for intervention, insulin injections for comparison, and glycemic control for outcome which led to only 3 articles. For the Trip database I searched Population “diabetes” Intervention “Continuous subcutaneous insulin” Comparison “Insulin injections” Outcome “glycemic control”, and it showed 12 results. However, these results were of no benefit to my question because many of them were outdated or had nothing to do with the effect of continuous subcutaneous insulin and multiple daily insulin injections on glycemic control.
Research Used:
| Citation | Misso, M.L., Egberts, K.J., Page, M., O’Connor, D. and Shaw, J. (2010), Cochrane review: Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Evid. -Based Child Health, 5: 1726-1867. https://doi-org.york.ezproxy.cuny.edu/10.1002/ebch.623 |
| Abstract | BackgroundType 1 diabetes is a metabolic disorder resulting from a defect in insulin secretion. Onset of type 1 diabetes mellitus may occur at any age, and it is one of the most common chronic diseases of childhood and adolescence. Since there are no interventions known to prevent onset, it is vital that effective treatment regimens are available. Glycemic control is maintained by replacement of insulin and may be in the form of ‘conventional’ insulin therapy (multiple injections per day) or continuous subcutaneous insulin infusion (CSII).ObjectivesTo assess the effects of CSII compared to multiple insulin injections (MI) in people with type 1 diabetes mellitus.Search strategyStudies were obtained from electronic searches of The Cochrane Library, MEDLINE, EMBASE and CINAHL.Selection criteriaStudies were included if they were randomized controlled trials comparing CSII with three or more insulin injections per day (MI) in people with type 1 diabetes mellitus.Data collection and analysisTwo authors independently assessed risk of bias and extracted characteristics of included studies. Authors contacted study investigators to obtain missing information. Generic inverse variance meta-analyses using a random-effects model were performed.Main resultsTwenty-three studies randomized 976 participants with type 1 diabetes to either intervention. There was a statistically significant difference in glycosylated hemoglobin A1c (HbA1c) favoring CSII (weighted mean difference -0.3% (95% confidence interval -0.1 to -0.4). There were no obvious differences between the interventions for non-severe hypoglycemia, but severe hypoglycemia appeared to be reduced in those using CSII. Quality of life measures suggest that CSII is preferred over MI. No significant difference was found for weight. Adverse events were not well reported, no information is available on mortality, morbidity, and costs.Authors’ conclusionsThere is some evidence to suggest that CSII may be better than MI for glycemic control in people with type 1 diabetes. Non-severe hypoglycemic events do not appear to be reduced with CSII. There is insufficient evidence regarding adverse events, mortality, morbidity, and costs.Plain Language SummaryContinuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitusType 1 diabetes results from a defect in insulin secretion, leading to elevated levels of plasma sugar or glucose and disturbances in carbohydrate, fat, and protein metabolism. Complications may affect the eyes, kidneys, nerves, and the cardiovascular system. Type 1 diabetes may occur at any age, and it is one of the most common chronic diseases of childhood and adolescence. Type 1 diabetes impacts heavily on the lifestyle of the individual as well as their families. Since there is no cure or prevention for type 1 diabetes, life-long insulin replacement and monitoring of blood glucose levels are required. It is vital that effective insulin therapy regimes are available for optimal management and to minimize blood glucose fluctuation (known as too low or too high blood sugar levels – hypoglycemia or hyperglycemia).Insulin therapy may be in the form of ‘conventional’ therapy of multiple (typically four) injections per day or continuous subcutaneous insulin infusion. Continuous subcutaneous insulin infusion involves attachment (via catheter on the outside of the body) to an insulin pump that is programmed to deliver insulin to match the individual’s needs, and doses are activated by the individual to cover meals and correct blood glucose fluctuation. Here we explore whether continuous subcutaneous insulin infusion is better than three or more insulin injections per day for good management of type 1 diabetes.Twenty-three studies randomized 976 participants with type 1 diabetes to either continuous subcutaneous insulin infusion or multiple injections. Seven of the 23 studies were performed in participants under 18 years of age and the remainder were performed in adults. Study duration ranged from six days to four years. The body of evidence suggests that continuous subcutaneous insulin infusion may be better than multiple injections for glycemic control in people with type 1 diabetes; continuous subcutaneous insulin infusion appears to provide no benefit for reducing non-severe hypoglycemic events. Future studies need to consider the short- and long-term adverse effects, mortality, morbidity, and costs of these interventions. |
| Link: | https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/10.1002/ebch.623 |
| Citation | Grunberger, G, Bhargava, A, Ly, T, et al. Human regular U-500 insulin via continuous subcutaneous insulin infusion versus multiple daily injections in adults with type 2 diabetes: The VIVID study. Diabetes Obes Metab. 2020; 22: 434–441. https://doi-org.york.ezproxy.cuny.edu/10.1111/dom.13947 |
| Abstract | AimTo compare the safety and efficacy of U500-R delivered by a novel, specifically designed U500-R insulin pump with U-500R delivered by multiple daily injections (MDI).MethodsThe phase 3 VIVID study randomized people with type 2 diabetes to U-500R by continuous subcutaneous insulin infusion (CSII) or MDI. Participants (aged 18–85 years) had HbA1c ≥7.5% and ≤12.0% and a total daily dose of insulin >200 and ≤600 U/day. After a 2-week transition to three times daily injections of U-500R, participants were treated for 24 weeks with U-500R by CSII or MDI. Treatment arms were compared using mixed model repeated measures analysis.ResultsThe study randomized 420 participants (CSII: 209, MDI: 211) with 365 completers. Mean changes from baseline were: HbA1c, −1.27% (−13.9 mmol/mol) with CSII and −0.85% (−9.3 mmol/mol) with MDI (difference − 0.42% [−4.6 mmol/mol], P <0.001); fasting plasma glucose, −33.9 mg/dL (−1.9 mmol/L) with CSII and 1.7 mg/dL (0.09 mmol/L) with MDI (difference − 35.6 mg/dL [−2.0 mmol/L], P <0.001); total daily dose, 2.8 U with CSII and 51.3 U with MDI (P < 0.001). Weight changes and rates of documented symptomatic and severe hypoglycemia were similar between groups; the CSII group had a higher rate of nocturnal hypoglycemia.ConclusionsIn type 2 diabetes requiring high doses of insulin, both methods of U-500R delivery lowered HbA1c. However, the CSII group attained greater HbA1c reduction with significantly less insulin. Individualized dose titration will be important to balance glycemic control with hypoglycemia risk. |
| Link: | https://dom-pubs-pericles-prod-literatumonline-com.york.ezproxy.cuny.edu/doi/10.1111/dom.13947 |
| Citation | Chai, T.Y.L., Farrell, K., and Holmes-Walker, D.J. (2023), Use of continuous subcutaneous insulin infusion versus multiple daily injections in emerging adults with type 1 diabetes is associated with better clinical engagement but not glycemic control. Intern Med J, 53: 255-261. https://doi-org.york.ezproxy.cuny.edu/10.1111/imj.15539 |
| Abstract | BackgroundLimited studies have compared outcomes between emerging adults with type 1 diabetes mellitus (T1D) attending a diabetes transition support programmed using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII).AimsTo assess glycemic control and service utilization in emerging adults with T1D on MDI or CSII attending a young adult diabetes clinic (YAC).MethodsA retrospective cohort analysis was conducted from January 2013 to December 2015. Data collected included clinic visits per year, after-hours mobile telephone use, diabetic ketoacidosis (DKA) admissions and all HbA1c levels. Independent t-test was used to compare continuous variables whilst Pearson’s Chi-squared test was used for categorical variables. Linear mixed effects models explored mean changes in HbA1c levels over time.ResultsOver 3 years, 318 youth with T1D (176 MDI, 121 CSII, 21 switched from MDI to CSII) attended our YAC. Aggregated mean HbA1c levels remained similar between modalities (CSII 9.1% vs MDI 9.3%; P = 0.23); however, mean change in HbA1c at 3 years was significantly increased in CSII users at 0.55% (95% CI 0.15–0.95; P < 0.01) compared with no significant change in MDI users. Clinic visits per year were improved in CSII users (CSII 2.8 vs MDI 2.5; P = 0.02), while DKA admissions remained similar between MDI and CSII users (3.6 admissions per 100 patient-years).ConclusionIn our YAC cohort, glycemic control in CSII and MDI users was similar but well below recommended international glycemic targets (HbA1c level < 7.0%). Despite increased clinical engagement occurring in CSII users, glycemic deterioration was observed over the 3 years. |
| Link: | https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/10.1111/imj.15539 |
| Citation | Pickup, J.C., and Sutton, A.J. (2008), Severe hypoglycemia and glycemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabetic Medicine, 25: 765-774. https://doi.org/10.1111/j.1464-5491.2008.02486.x |
| Abstract | Aims Continuous subcutaneous insulin infusion (CSII) is a recommended treatment for reducing severe hypoglycemia in Type 1 diabetes, but the change in hypoglycemia compared with multiple daily insulin injections (MDI) is unclear. We therefore conducted a meta-analysis comparing severe hypoglycemia and glycemic control during CSII and MDI.Methods Databases and literature (1996–2006) were searched for randomized controlled trials (RCTs) and before/after studies of ≥ 6 months’ duration CSII and with severe hypoglycemia frequency > 10 episodes/100 patient years on MDI.Results In 22 studies (21 reports), severe hypoglycemia during MDI was related to diabetes duration (P = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, P = 0.036). Severe hypoglycemia was reduced during CSII compared with MDI, with a rate ratio of 2.89 (95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19 (2.86 to 6.13) for all studies]. The reduction was greatest in those with the highest initial severe hypoglycemia rates on MDI (P < 0.001). The mean difference in glycated hemoglobin (HbA1c) between treatments was less for RCTs [0.21% (0.13–0.30%)] than in before/after studies [0.72% (0.55–0.90%)] but strongly related to the initial HbA1c on MDI (P < 0.001).Conclusions The severe hypoglycemia rate in Type 1 diabetes was markedly less during CSII than MDI, with the greatest reduction in those with most severe hypoglycemia on MDI and those with the longest duration of diabetes. The biggest improvement in HbA1c was in those with the highest HbA1c on MDI. |
| Link: | https://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.2008.02486.x |
| Citation | Mitra M. Fatourechi and others, Hypoglycemia with Intensive Insulin Therapy: A Systematic Review and Meta-Analyses of Randomized Trials of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections, The Journal of Clinical Endocrinology & Metabolism, Volume 94, Issue 3, 1 March 2009, Pages 729–740, https://doi.org/10.1210/jc.2008-1415 |
| Abstract | AbstractContext: Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear.Objective: The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia.Data Sources: We searched electronic databases between 2002 and March 2008.Study Selection: We selected published randomized trials of CSII vs. MDI.Data Extraction: Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events.Data Synthesis: We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, −0.2%; 95% confidence interval (CI), −0.3, −0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificant fewer minor hypoglycemia episodes per patient per week (−0.08; 95% CI, −0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; Pinteraction = 0.03). Outcomes were not different in patients with type 2 diabetes.Conclusions: Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data. |
| Link: | https://academic.oup.com/jcem/article/94/3/729/2596271 |
| Citation | Chen, J, Fan, L, Peng, X, Ilag, L, Ly, T, Johnson, J. Patient-reported outcomes in a study of human regular U-500 insulin delivered by continuous subcutaneous insulin infusion or multiple daily injections in patients with type 2 diabetes. Diabetes Obes Metab. 2021; 23: 240–244. https://doi-org.york.ezproxy.cuny.edu/10.1111/dom.14191 |
| Abstract | Human regular U-500 insulin (U-500R) provides both basal and prandial coverage to people with diabetes. As part of the VIVID study, we studied patient-reported outcomes (PRO) of U-500R delivered by multiple daily injections (MDI, n = 211) and continuous subcutaneous infusion using a novel U-500R pump (CSII, n = 209). Treatment-Related Impact Measure for Diabetes (TRIM-D) for Diabetes Device (TRIM-DD) questionnaires were administered at weeks 0, 14 and 26. TRIM scores with effect sizes (ES) for within-group and between-group change were reported. All TRIM-D scores significantly improved from baseline for both groups (P < .001). The Diabetes Management domain had the greatest improvement, 16.3 (ES = 0.85) and 10.6 (ES = 0.51) for CSII and MDI, respectively. At the study end, the CSII group had significantly higher TRIM-D scores than the MDI group (P < .05). Most TRIM-DD scores had small within-group improvements and were not different between groups. People with type 2 diabetes on U-500R by either CSII or MDI reported improvement in PRO, particularly in Diabetes Management, Treatment Burden, and Psychological Health domains, with greater improvement in the CSII group. In terms of delivery device and function, the CSII and MDI methods were similarly acceptable. |
| Link: | https://dom-pubs-onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/full/10.1111/dom.14191 |
Summary of Evidence:
| Author (Date) | Level of Evidence | Sample/Setting(# of subjects/ studies, cohort definition etc.) | Outcomes Studied | Key Findings | Limitations and Biases |
| Marie L Misso et al.(2010) | Systematic review | All published and unpublished randomized and quasi-randomized controlled trials designed to compare people with type 1 diabetes taking insulin in the form of either continuous subcutaneous insulin infusion (CSII) or multiple insulin injections.Males and females with type 1 diabetes of any age taking insulin treatment were considered in this review.To remain consistent with changes in classification and diagnostic criteria through the years, diagnosis of type 1 diabetes status was based upon the diagnostic criteria valid at the time of beginning the study. Acceptable diagnostic criteria included those described by the National Diabetes Data Group standards, the World Health Organization, and the American Diabetes Association.Insulin preparation and dose of insulin varied depending on the study, therefore all insulin preparations and doses were accepted as interventions.searched the following sources for the identification of studies up to 20 July 2009: The Cochrane Library; MEDLINE; EMBASE; and CINAHL.Twenty-three randomized controlled trials (RCTs) meeting the inclusion criteria of this review were identified.In total, 976 people with type 1 diabetes took part in the 23 randomized controlled studies. Seven of the 23 studies were performed in participants under 18 years of age. | Primary outcomes:· glycemic control (glycosylated hemoglobin A1c (HbA1c), daily mean blood glucose, fasting blood glucose or postprandial blood glucose)· number of overall, severe, and non-severe hypoglycemic episodes· quality of life (ideally measured using a validated instrument). Secondary outcomes· weight· insulin requirement to maintain glycemic control.· number and severity of adverse events (e.g., ketoacidosis, local infections)· diabetes late complications· mortality· costs | The data indicates that there is no relevant benefit of one intervention over the other for reducing non-severe hypoglycemic events.The data indicates that CSII may be better than MI for reducing the incidence of severe hypoglycemic events.Data suggest that most participants were more satisfied with CSII than MI.The mean difference of HbA1c was estimated to be -0.3% (95% CI -0.5 to -0.1) in favor of CSII compared with MI.The mean difference of fasting blood glucose was estimated to be -14 mg/dl (95% CI -24 to -4) in favor of CSII compared with MI.The mean difference of post prandial blood glucose was estimated to be -4 mg/dl (95% CI -11 to 2) in favor of CSII compared with MI.The mean difference of daily insulin requirement (U) was estimated to be -7 U (95% CI -11 to -3) in favor of CSII compared with MI | None of the studies reported on morbidity.None of the studies reported on mortality.Costs were not addressed in any of the included studies. Six cross-over studies were not adequately analyzed and did not report correlations between baseline and end-of-study data, therefore ignoring within-person variation. The selection criteria specified that MI required three or more injections per day, therefore many studies were excluded because their definition of MI was two or more injections per day. Many different scales and units were used to report measures of non-severe and severe hypoglycemia and quality of life. There were insufficient studies to conduct meta-analyses for each of the scales and units, and as a result, our interpretation of the overall effects of the interventions on these outcomes is subjective and open to bias. |
| Grunberger, G, Bhargava, A, Ly, T, et al. (2019) | Randomized control trial | The VIVID study was a randomized, controlled, multicenter, open-label, parallel design, 26-week, phase 3 study of U-500R delivered by CSII compared with U-500R delivered by MDI in participants with type 2 diabetes who require high doses of insulin.Participants were aged 18–85 years, had a body mass index of 25–50 kg/m2, an HbA1c of ≥7.5% and ≤12.0%, and a total daily dose (TDD) of insulin >200 U, but ≤600 U of U-500 insulin by injection or non-U-500 insulin by injection or CSII.Participants were excluded for liver disease, stage 4 or higher kidney disease, class III or IV cardiac disease, or a history of more than one episode of severe hypoglycemia requiring the assistance of another person within the last 6 months.Concomitant glucose-lowering therapy with metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium glucose co-transporter-2 inhibitors (SGLT2is) and/or pioglitazone (doses ≤30 mg/day) was permitted.Assignment to MDI or CSII treatment arms was determined by a computer-generated random sequence using an interactive web response system, with stratification by HbA1c ≥8.5% or <8.5%, non-users versus users of GLP-1RAs or SGLT2is, and U-500R at entry versus other insulins.After randomization, both groups underwent a 2-week transition to U-500R by MDI, whereupon participants who had been randomized to CSII switched from MDI to the investigational U-500 system.Treatment was continued for 26 weeks. All participants were instructed to record seven-point SMBG profiles on any two non-consecutive days in the 2 weeks prior to visits at weeks 0, 14 and 26; profiles were to include a weekend day, if possible. A central laboratory was used for analysis of FPG at weeks 0, 14 and 26, and for analysis of HbA1c at weeks 0, 8, 14, 20 and 26.A total of 632 participants were screened; 420 were randomly assigned to treatment (CSII: 209, MDI: 211). Of these, 340 participants were in Group A (CSII: 170, MDI: 170). The study was conducted between October 20, 2015, and May 9, 2017, at 55 sites in the USA and Puerto Rico. A total of 365 participants completed the study. | The primary objective of the VIVID study was to show in Group A that the change in HbA1c of the U-500R CSII group was non-inferior to that of the U-500R MDI group from baseline to week 26.The key secondary objectives, which will be presented for the all-randomized population without adjustment for multiplicity, were to show that U-500R delivered by CSII was superior to U-500R by MDI in the following variables: change from baseline of fasting plasma glucose (FPG); change from baseline of HbA1c; and the proportion of participants achieving HbA1c target values of <7% and <7.5%.Comparisons were performed in the all-randomized population on the proportions of participants achieving other HbA1c targets (≤6.5% and <8.0%); change in seven-point self-monitored blood glucose (SMBG) profile, including mean SMBG for each time point measurement; change in TDD; rate and incidence of hypoglycemia; and change in body weight.The categories of hypoglycemia analyzed in the study were documented: symptomatic hypoglycemia (signs/symptoms with a blood glucose level of ≤70 mg/dL), nocturnal hypoglycemia (any hypoglycemic event, documented or severe, occurring between bedtime and waking), and severe hypoglycemia (an event such that the patient required the assistance of another person). | The CSII group had significantly lower pre-morning meal and 2-hour post morning meal blood glucose compared with the MDI group, while the MDI group had significantly lower 2-hour post evening meal blood glucose.The CSII group had significantly greater proportions of participants achieving specific HbA1c target values at week 26.Body weight change from baseline to week 26 was not significantly different between groups.There were no significant differences in incidences or rates (weeks 0–26) of documented symptomatic hypoglycemia or severe hypoglycemia between treatment groups.The CSII group had a higher nocturnal hypoglycemia rate at both blood glucose cut-offs (<54 and ≤70 mg/dL). However, nocturnal hypoglycemia incidence was similar between groups with most participants having 0 to 5 events during this 26-week study.There were 17 severe hypoglycemia events in 16 participants: 12 events in 11 participants in the CSII group and five events in five participants in the MDI group. All participants with severe hypoglycemic events fully recovered.A total of 57 participants (13.6%) experienced at least one serious adverse event (SAE) after randomization; 34 (16.3%) in the CSII group and 23 (10.9%) in the MDI group.Treatment-emergent adverse events (TEAEs) possibly related to study drug were reported by 29 participants (13.9%) in the CSII group and 22 participants (10.4%) in the MDI group. | The duration of insulin action was increased from a maximum of 8 hours for the U-100 Omnipod System to a maximum of 12 hours to allow the investigator flexibility in personalizing the insulin on board calculation for people using U-500.Other settings were calibrated for U-500; for example, the maximum bolus was 150 units, maximum basal rate was 150 U/h, and the minimum dose increment was 0.25 U.Majority of the patients were white men therefore it is uncertain if these results applying across different genders and ethnicities. |
| Chai, T.Y.L., Farrell, K., and Holmes-Walker, D.J., (2021) | Retrospective cohort analysis | A retrospective cohort analysis was performed on emerging adults with T1D who were treated at the YAC from January 2013 to December 2015.Data were analyzed using the IBM Statistical Package for Social Science, version 25 and R Programmer, version 3.5.3 Results were divided by treatment group (MDI vs CSII user). Between January 2013 and December 2015, 1907, HbA1c levels were performed on 318 participants, aged 15−25 years, with T1D who had registered with the YAC and had attended at least one clinic appointment. Of the 318 participants, 176 (55%) remained on MDI, 121 (38%) remained on CSII and 21 (7%) changed from MDI to CSII (switched group). None of the participants changed from CSII to MDI over the 3 years.Demographically, CSII and MDI users were similar in age, ethnicity, and duration of T1D. | Meaningful improvements in multiple categories such as glycemic control, clinic engagement, and DKA admission rates. | Aggregated mean HbA1c values did not differ between either treatment modalities, although a greater proportion of MDI users compared to CSII users had HbA1c level ≥ 11.0%, indicating extremely poor glycemic control. In terms of mean change in HbA1c level over the 3 years, there was no significant change in HbA1c levels in MDI users, while CSII users were observed to have a significant increase in their HbA1c levels of 0.55%.Of the 21 patients who switched from MDI to CSII over the 3 years, no significant mean change in HbA1c levels occurred while on MDI or while on CSII.Mean clinic visits per year were significantly greater in CSII users compared with MDI users, while mean interval between clinic visits was significantly less in CSII users.The use of the after-hours mobile telephone support service was significantly higher in CSII compared with MDI users, both in terms of number of occasions of service per year.DKA admission rates were similar for both treatment modalities at 3.6 per 100 patient-years, whilst in the switched group, a lower DKA admission rate occurred at 3.2 per 100 patient-years.In participants with HbA1c level ≥11.0%, MDI users were more likely to be admitted with DKA during the study period in comparison with CSII users.The primary cause for DKA admissions in MDI users with HbA1c levels ≥11.0% was non-adherence to insulin therapy, while in CSII users it was due to failure of their insulin pump or insulin pump set. | CSII users were more likely to be female and of white background.A large proportion of participants in the study were white, and a limitation is that our findings may not be applicable to other multiethnic populations. |
| Pickup, J.C., and Sutton, A.J. (2008), | Systematic review | For the study of severe hypoglycemia, they selected for inclusion in the meta-analysis only trials in Type 1 diabetes of ≥ 6 months duration of CSII, where the rate of severe hypoglycemia during MDI was > 10 episodes/100 patient years of treatment, and the study was published no earlier than 1996.The search terms used were insulin pump therapy, insulin infusion system, insulin pump, continuous subcutaneous insulin infusion and CSII.All 22 studies reporting severe hypoglycemia rates used MDI based on isophane- or Lente-type intermediate-acting insulin in combination with regular or monomeric insulin at meals. Ten studies (45.5%) were in children or adolescents and 12 studies were in adults. A total of 1414 Type 1 diabetic subjects received either MDI or insulin pump therapy for a mean CSII duration of 6–48 months. | Severe hypoglycemia was recorded as episodes/100 patient years of treatment. Both the rate on MDI and the rate ratio for episodes on MDI compared with CSII were considered as outcome measures.Assessed overall glycemic control using HbA1c and the mean difference in this quantity on MDI compared with CSII in each trial was used as the outcome measure. | The pooled severe hypoglycemia event rate during MDI was 62 events per 100 patient years.Adult subjects with diabetes had a greater frequency of severe hypoglycemia on MDI.There was a strong linear association between severe hypoglycemia rate during MDI and mean diabetes duration.In RCTs, the random effect meta-analysis for severe hypoglycemia rates showed that severe hypoglycemia was markedly reduced during CSII compared with MDI, with a rate ratio of 2.89.Mean age was also a highly significant predictor of treatment effect, with older subjects having a significantly greater reduction in severe hypoglycemia on CSII compared with MDI.In RCTs, the random effect meta-analysis for the mean difference in HbA1c between MDI and CSII showed better control during insulin pump therapy: HbA1c difference 0.21%. | There were no findings on any trials comparing CSII and MDI based on the newer long-acting insulin analogues where severe hypoglycemia could be analyzed, and the subjects were therefore not notably at risk of severe hypoglycemia.The conclusions on HbA1c are based on a relatively small number of trials concerning glargine and none using detemir.Because the proportion of short-acting insulin that was regular human or analogue for each study was either not stated or a mixture of the two types in a high proportion of studies, they did not compare severe hypoglycemia in the two MDI regimens. |
| Mitra M. Fatourechi et al(2009) | Systematic review and meta-analysis | RCTs of intensive insulin therapy delivered either as CSII (insulin pump) or as MDIs in adults or children with diabetes of any kind, published in any language, were eligible for this review. Searched electronic databases for eligible RCTs in MEDLINE (PubMed), EMBASE, and Cochrane’s CENTRAL, from 2002 until August 2007 using terms that referred to both insulin and randomized trials. Initial search of the literature yielded 101 publications, of which 55 were relevant to this review based on titles and abstracts. After review, we found 12 eligible reports of 11 RCTs. The updated search in March 2008 led to the identification of four additional RCTs for a total of 15 included RCTs. | The outcomes measured were glycemic control, severe hypoglycemia, nocturnal hypoglycemia, and minor hypoglycemia. | Compared with MDI, CSII in patients with type 1 diabetes reduced HbA1c by 0.2%; this result was consistent across trials and across the subgroups examined.There was a nonsignificant trend toward worse glycemic control with CSII in patients with type 2 diabetes.There was no significant interaction between insulin use (analog insulin only vs. other combinations) and the risk of nocturnal hypoglycemia with CSII vs. MDI.Meta-analyses showed that in patients with type 1 diabetes, CSII is associated with a slightly lower HbA1c of uncertain clinical significance, without a significant difference in the hypoglycemia risk in adolescents and adults; children with type 1 diabetes enrolled in parallel trials had a higher risk of minor hypoglycemia when treated with CSII.Did not find significant differences in glycemic control or hypoglycemia outcomes in patients with type 2 diabetes treated with CSII vs. MDI. | The relative effects of CSII vs. MDI remain unclear for patients with type 2 diabetes at high risk of hypoglycemia because patients with prior severe hypoglycemia were excluded from both trials enrolling patients with type 2 diabetes.The main limitations of this systematic review refer to the paucity of evidence in patients at high risk of hypoglycemia, such as patients with a history of recurrent severe hypoglycemia, and patients with hypoglycemia unawareness.Many of the trials did not have exclusion criteria for prior hypoglycemia awareness, these tended to be smaller trials enrolling patients with more recent onset of diabetes.The largest trials of type 1 diabetes enrolling the populations at highest risk—those with long-standing type 1 diabetes—did exclude patients with prior history of severe hypoglycemia.Many studies were conducted at centers with strong expertise in pump therapy; it can be speculated on whether academic centers having an interest in improving MDI therapy may have had a different effect. |
| Chen, J, Fan, L, Peng, X, Ilag, L, Ly, T, Johnson, J. (2020) | Randomized control trial | Participants with T2D and inadequate glycemic control were randomized to receive U-500R treatment by CSII using the investigational Omni pod DASH™ U-500 Insulin Management System; (n = 209) or MDI (n = 211).Two validated PRO measures, Treatment-Related Impact Measure for Diabetes (TRIM-D) and for Diabetes Device (TRIM-DD), were administered at weeks 0 14 and 26, or at the time of early termination.All TRIM scores and their changes from baseline to weeks 14 and 26 were analyzed using a mixed-effects model for repeated measures approach.Besides baseline measures, the MMRM model included the following fixed effects: treatment device, weeks on treatment, interaction between treatment and weeks, and stratification factors. | The outcomes measured were treatment Burden, Daily Life, Diabetes Management, Compliance, and Psychological Health. Device Function and Bother of Device were also considered. | U-500R treatment by both CSII and MDI had a positive effect on treatment-related well-being and patient functioning, with a greater improvement in the CSII group.Results from the MDI group are consistent with the results from a previous study in patients with T2D requiring high dose insulin and transitioning from U-100 MDI to U-500R in which the TRIM-D scores demonstrated clinically relevant and significant improvements.Improvement in the Diabetes Management domain in the CSII group over the MDI group was prominent, consistent with the fact that the CSII group showed statistically significant improvement in HbA1c, and fasting plasma glucose levels compared with the MDI group, as well as a statistically greater percentage of patients reaching the HbA1c target of <7% and <7.5%.Consistent with better glycemic control in the CSII group4 was the small to moderately higher Psychological Health score change compared with the MDI group, as the psychological component of treatment is often driven by efficacy.The CSII group also showed a moderate magnitude of improvement over the MDI group in the Treatment Burden domain, which is probably a reflection of pump therapy benefits such as flexibility, discretion, convenience, embedded dose calculation and dosing precision. | One weakness is the open label design. The favorable CSII results over MDI found in this study may be limited to people with T2D who are able to manage diabetes with CSII, given that seven patients allocated to the CSII group discontinued the treatment for various reasons. |
Conclusion
The first article utilizes a systematic review to assess the effects of continuous subcutaneous insulin compared to multiple daily insulin injections. It answered my questions directly by comparing both treatment options impact on glycemic control and quality of life. It also took it a step further and included a comparison within regard to non-severe hypoglycemic events.
The second article uses a clinical trial to compare the efficacy of using U-500R by continuous subcutaneous insulin infusion compared to multiple daily injections. It directly answers my questions by comparing both treatment options effects on lowering A1C and fasting blood glucose. It also factors in quality of life by measuring effects on weight gain and clinically relevant hypoglycemia.
The third article uses a retrospective cohort to compare continuous subcutaneous insulin infusion with multiple daily injections in the setting of type 1 diabetes. It compares the effects on glycemic control and quality of life through measurements of clinical engagement and DKA admission rates.
The fourth article using a meta-analysis to assess the efficacy of multiple daily injections and continuous subcutaneous insulin infusion. It compared different aspects of each treatment such as cases of severe hypoglycemia and glycemic control. This article however did not consider any aspects regarding quality of life.
The fifth article using a meta-analysis to assess the efficacy of multiple daily injections and continuous subcutaneous insulin infusion. It compared different aspects of each treatment such as severe hypoglycemia, nocturnal hypoglycemia, and minor hypoglycemia. This article like the previous one did not factor in any measurements related to quality of life. This article does however look at both type 1 and type 2 diabetes when comparing the efficacy of both treatment options.
The sixth article uses a randomized control trial to examine patient reported outcomes regarding continuous subcutaneous insulin infusion compared to multiple daily injections. Unlike the other articles this study approached the question from more of a patient satisfaction view by measuring outcomes such as treatment burden, daily life, diabetes management, compliance, psychological health, device functioning, and bother of device.
All six of the articles have differing opinions on whether continuous subcutaneous insulin infusion is more effective at glycemic control than multiple daily insulin injections. The first, second, sixth, and fifth articles are similar in the sense that both conclude that continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections at controlling glucose levels, more specifically A1C when referring to the second and fifth articles. However, the first article also concluded that continuous subcutaneous insulin infusion had no effect at reducing non severe hypoglycemic events. Furthermore, the third article contradicts the others in that it concludes that both methods of delivery are equal in efficacious and even goes as far to say that both are not up to par. The fourth article brings a completely different deduction into the picture by concluding that multiple daily insulin injections are more efficient than continuous subcutaneous insulin infusion at reducing the rate of hypoglycemia while also decreasing A1C.
Clinical Bottom Line:
Overall, all the articles have weaknesses through various biases which factor into the overall weight of evidence for each article. In the second and third articles many of the participants were Caucasian so it can be said these studies may be limited due to the lack of inclusivity of other races and genders, which may have affected the results. The credibility of the results of the first article can be brought into question seeing that it did not factor in many outcomes such as morbidity, mortality, and cost, which are all big factors when it comes to which treatment modality should be suggested for a patient. The fourth article is limited seeing that the conclusions on hemoglobin A1C are based on a relatively small number of trials concerning only one form of insulin. Within the fifth article one limitation that can be appreciated is the fact that many studies were conducted at centers with strong expertise in pump therapy therefore it cannot be excluded that the study may have had different results if the centers also had strong expertise in the multiple daily injection method. The sixth article has its limitations in that the favorable continuous subcutaneous infusion results over multiple daily injections found in this study may be limited to people with type 2 diabetes.
The clinical bottom line as outlined in all the articles is that studies have shown that there are mixed results on whether continuous subcutaneous insulin infusion is more effective at glycemic control than multiple daily insulin injections. Due to the varying studies, I think it is safe to say that more research needs to be done around this topic before it is said that one delivery method of insulin is better than the other. Therefore, in clinical practice patients should be presented with both options, while also weighing into account the cost of each method as well as the likelihood of adherence. It may be easier for some people to adhere to the continuous subcutaneous insulin infusion because it requires less “work” and is technology based. However, some people may find it less complicated to simply do multiple daily injections because it may be difficult for them to learn how to work the insulin pump. When a patient is being presented with both options for these aspects should be considered and the patient and clinician should use shared decision making to decide on a delivery method that best suits said individual patient.
