Hsin-Chieh Yeh, PhD; Todd T. Brown, MD, PhD; Nisa Maruthur, MD, MHS; Padmini Ranasinghe, MD, MPH; Zackary Berger, MD, PhD; Yong D. Suh, MBA, MSc; Lisa M. Wilson, ScM; Elisabeth B. Haberl, BA; Jessica Brick, MD; Eric B. Bass, MD, MPH; Sherita Hill Golden, MD, MHS
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Dr. Christine Chang, Task Order Officer, for her support throughout the project and for helpful suggestions for improving the clarity and presentation of the findings; Dr. Ari Eckerman and research assistants Drs. Elie Donath and Ghanshyam Palamaner Subash Shantha for their help in reviewing articles; Dr. Felicia Hill-Briggs for her consultation on quality-of-life outcomes; and the late Dr. Christopher Saudek for his contribution and guidance in the early stage of this work.
Grant Support: By the AHRQ.
Potential Conflicts of Interest: Disclosures can be also viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0156.
Requests for Single Reprints: Sherita Hill Golden, MD, MHS, Division of Endocrinology and Metabolism and the Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, MD 21287; e-mail, sahill@jhmi.edu.
Current Author Addresses: Drs. Yeh and Maruthur: Division of General Internal Medicine and the Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins University, 2024 East Monument Street, Suite 2-500, Baltimore, MD 21287.
Dr. Brown: Division of Endocrinology and Metabolism, The Johns Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, MD 21287.
Dr. Ranasinghe: Division of General Internal Medicine, The Johns Hopkins University, 600 North Wolfe Street, Park 207, Baltimore, MD 21287.
Dr. Berger: Division of General Internal Medicine and Evidence-Based Practice Center, The Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287.
Mr. Suh: Johns Hopkins University School of Medicine, Broadway Research Building, 733 North Broadway, Suite 137, Baltimore, MD 21205-2196.
Ms. Wilson, Ms. Haberl, and Dr. Bass: Evidence-Based Practice Center, The Johns Hopkins University, 624 North Broadway, Baltimore, MD 21205.
Dr. Brick: Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115.
Dr. Hill Golden: Division of Endocrinology and Metabolism and the Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, MD 21287.
Author Contributions: Conception and design: H.C. Yeh, T.T. Brown, N. Maruthur, P. Ranasinghe, Z. Berger, L.M. Wilson, E.B. Haberl, J. Brick, E.B. Bass, S. Hill Golden.
Analysis and interpretation of the data: H.C. Yeh, T.T. Brown, N. Maruthur, P. Ranasinghe, Z. Berger, Y.D. Suh, E.B. Bass, S. Hill Golden.
Drafting of the article: H.C. Yeh, T.T. Brown, P. Ranasinghe, Z. Berger, Y.D. Suh, S. Hill Golden.
Critical revision of the article for important intellectual content: H.C. Yeh, T.T. Brown, N. Maruthur, P. Ranasinghe, Z. Berger, E.B. Bass, S. Hill Golden.
Final approval of the article: H.C. Yeh, T.T. Brown, N. Maruthur, P. Ranasinghe, E.B. Bass, S. Hill Golden.
Provision of study materials or patients: L.M. Wilson.
Statistical expertise: H.C. Yeh, L.M. Wilson.
Obtaining of funding: E.B. Bass.
Administrative, technical, or logistic support: L.M. Wilson, E.B. Haberl, E.B. Bass.
Collection and assembly of data: H.C. Yeh, T.T. Brown, N. Maruthur, Y.D. Suh, L.M. Wilson, E.B. Haberl, J. Brick, S. Hill Golden.
Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring.
To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue–based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions.
33 randomized, controlled trials in children or adults that compared CSII with MDI (n = 19), rt-CGM with SMBG (n = 10), or sensor-augmented insulin pump use with MDI and SMBG (n = 4).
2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data.
In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, −0.26% [95% CI, −0.33% to −0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, −0.68% [CI, −0.81% to −0.54%]). Little evidence was available on other outcomes.
Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus.
Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia.
Agency for Healthcare Research and Quality.
Appendix Table 1.
Search Strategies
Appendix Table 2.
Health-Related QOL Assessment Tools Used in Each Category
Summary of evidence search and selection.
CENTRAL= Cochrane Central Register of Controlled Trials; CSII = continuous subcutaneous insulin infusion; HbA1c = hemoglobin A1c; MDI = multiple daily injections; rt-CGM = real-time continuous glucose monitoring; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
* Total number of articles may exceed the number in the corresponding box because articles could be excluded for more than 1 reason.
Appendix Table 3.
Population Characteristics of Studies Comparing Methods of Insulin Delivery or Glucose Monitoring for Diabetes Mellitus
Table 1.
Summary of Findings and Strength of Evidence Comparing Insulin Delivery and Glucose-Monitoring Methods for Reported Outcomes
Appendix Table 4.
Study Quality and Risk of Bias Assessment of Clinical Trials Comparing Methods of Insulin Delivery or Glucose Monitoring for Diabetes Mellitus
Mean between-group difference in the change from baseline HbA1c comparing CSII with MDI among children and adolescents with T1DM, adults with T1DM, and adults with T2DM.
Error bars represent 95% CIs. Shaded boxes represent individual study point estimates. Box size corresponds to weight of study. CSII = continuous subcutaneous insulin infusion; HbA1c = hemoglobin A1c; MDI = multiple daily injections; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Appendix Table 5.
Summary of the Evidence of the Comparative Effectiveness of CSII With MDI, rt-CGM With SMBG, and SAP Therapy With MDI and SMBG in Children, Adolescents, or Adults With T1DM or T2DM
Pooled IRR for severe hypoglycemia comparing CSII with MDI among children and adolescents with T1DM.
Error bars represent 95% CIs. Shaded boxes represent individual study point estimates. Box size corresponds to weight of study. CSII = continuous subcutaneous insulin infusion; IRR = incidence rate ratio; MDI = multiple daily injections; T1DM = type 1 diabetes mellitus.
Pooled OR for severe hypoglycemia comparing CSII with MDI among adults with T1DM.
Error bars represent 95% CIs. Shaded boxes represent individual study point estimates. Box size corresponds to weight of study. CSII = continuous subcutaneous insulin infusion; MDI = multiple daily injections; OR = odds ratio; T1DM = type 1 diabetes mellitus.
Comparison of rt-CGM with SMBG and SAP use with MDI plus SMBG among patients with T1DM.
Mean between-group difference in the change from baseline HbA1c among patients with T1DM comparing rt-CGM with SMBG and SAP with MDI plus SMBG (top). Pooled OR of severe hypoglycemia comparing rt-CGM with SMBG among patients with T1DM (bottom). Error bars represent 95% CIs. Shaded boxes represent individual study point estimates. Box size corresponds to weight of study. HbA1c = hemoglobin A1c; MDI = multiple daily injections; OR = odds ratio; rt-CGM = real-time continuous glucose monitoring; SAP = sensor-augmented pump for insulin delivery; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus.
* Patients aged 15–24 y.
† Patients aged 8–14 y.
‡ Patients aged >25 y.
Adherence with sensor use and mean between-group difference between rt-CGM and SMBG in HbA1c changed from baseline.
HbA1c = hemoglobin A1c; rt-CGM = real-time continuous glucose monitoring; SMBG = self-monitoring of blood glucose.
Table 2.
Summary of the Subgroup Analyses in the Between-Group Change From Baseline HbA1c Among Patients With T1DM Comparing rt-CGM with SMBG
Between-group difference between rt-CGM and SMBG in time spent in hypoglycemic range changed from baseline among patients with T1DM.
Boxes indicate individual study point estimates. The box size denotes the weight of the study, with larger boxes contributing more to the pooled estimate. The width of the horizontal lines represents the 95% CI for each study. The diamond at the bottom of the figure indicates the 95% CI for the random-effects pooled estimate. Test for heterogeneity: Q = 4.24 (P = 0.52). rt-CGM = real-time continuous glucose monitoring; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus.
* Patients aged >25 y.
‡ Patients aged 15–24 y.
Between-group difference between rt-CGM and SMBG in time spent in hyperglycemic range changed from baseline among patients with T1DM.
Boxes indicate individual study point estimates. The box size denotes the weight of the study, with larger boxes contributing more to the pooled estimate. The width of the horizontal lines represents the 95% CI for each study. The diamond at the bottom of the figure indicates the 95% CI for the random-effects pooled estimate. Test for heterogeneity: Q = 5.80 (P = 0.33). rt-CGM = real-time continuous glucose monitoring; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus.
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Yeh H, Brown TT, Maruthur N, Ranasinghe P, Berger Z, Suh YD, et al. Comparative Effectiveness and Safety of Methods of Insulin Delivery and Glucose Monitoring for Diabetes Mellitus: A Systematic Review and Meta-analysis. Ann Intern Med. ;157:336–347. doi: 10.7326/0003-4819-157-5-201209040-00508
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© 2019
Published: Ann Intern Med. 2012;157(5):336-347.
DOI: 10.7326/0003-4819-157-5-201209040-00508
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism, High Value Care.
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