Journal Watch: Continuous Glucose Monitoring and Risk of Hypoglycemia


Originally published May 1, 2018 by Kathleen Wyne, MD, PhD, FACE, FNLA

These papers published in the December 2017 issue of Diabetes Care summarize the recent progress in continuous glucose monitoring (CGM) measurements and interpretation, describe the properties and limitations of available CGM systems, propose minimum standards for these systems, address practical issues related to daily use and discuss proposed measures of glycemic control other than A1C, including categories of hypoglycemia and proportions of time in glucose target ranges during CGM.

Reading the editorial first and then the position statements in any order followed by reading the editorial again would be a reasonable strategy to tackle these valuable but complex issues.

Editorial

Maturation of CGM and Glycemic Measurements Beyond HbA1c—A Turning Point in Research and Clinical Decisions. Matthew C. Riddle, Hertzel C. Gerstein and William T. Cefalu. Diabetes Care, 2017 Dec; 40 (12): 1611-1613. https://doi.org/10.2337/dci17-0049

Position Statements

I. Improving the Clinical Value and Utility of CGM Systems: Issues and Recommendations. A Joint Statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. John R. Petrie, Anne L. Peters, Richard M. Bergenstal, Reinhard W. Holl, G. Alexander Fleming and Lutz Heinemann. Diabetes Care, 2017 Dec;40(12):1614-1621. https://doi.org/10.2337/dci17-0043

II. Standardizing Clinically Meaningful Outcome Measures beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Gina Agiostratidou, Henry Anhalt, Dana Ball, Lawrence Blonde, Evgenia Gourgari, Karen N. Harriman, Aaron J. Kowalski, Paul Madden, Alicia H. McAuliffe-Fogarty, Molly McElwee-Malloy, Anne Peters, Sripriya Raman, Kent Reifschneider, Karen Rubin and Stuart A. Weinzimer. Diabetes Care, 2017 Dec;40(12):1622-1630. https://doi.org/10.2337/dc17-1624

III. International Consensus on Use of Continuous Glucose Monitoring. Thomas Danne, Revital Nimri, Tadej Battelino, Richard M. Bergenstal, Kelly L. Close, J. Hans DeVries, Satish Garg, Lutz Heinemann, Irl Hirsch, Stephanie A. Amiel, Roy Beck, Emanuele Bosi, Bruce Buckingham, Claudio Cobelli, Eyal Dassau, Francis J. Doyle III, Simon Heller, Roman Hovorka, Weiping Jia, Tim Jones, Olga Kordonouri, Boris Kovatchev, Aaron Kowalski, Lori Laffel, David Maahs, Helen R. Murphy, Kirsten Nørgaard, Christopher G. Parkin, Eric Renard, Banshi Saboo, Mauro Scharf, William V. Tamborlane, Stuart A. Weinzimer and Moshe Phillip. Diabetes Care, 2017 Dec;40(12):1631-1640. https://doi.org/10.2337/dc17-1600


Efficacy and Safety of Semaglutide versus Dulaglutide as Add-on to Metformin in Subjects with Type 2 Diabetes

Study Title Acronym: SUSTAIN 7

ClinicalTrials.gov Identifier: NCT02648204

References (related):

  1. Pratley, R., Aroda, V, Lingvay, I., Lüdemann, J., Andreassen, C., Navarria, A. and Viljoen, A.; SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. (2018). Lancet Diabetes Endocrinol, Jan 31. PMID: 29397376. [Epub ahead of print]
  2. Semaglutide (Ozempic)–another injectable GLP-1 receptor agonist for type 2 diabetes. [No authors listed] Med Lett Drugs Ther. 2018 Jan 29;60(1539):19-21. PMID: 29364197
  3. Marso, S., Bain, S., Consoli, A., Eliaschewitz, F., Jódar, E., Leiter, L., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M., Woo, V., Hansen, O., Holst, A., Pettersson, J., Vilsbøll, T.; SUSTAIN-6 Investigators. (2018). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med, 375(19), pp.1834-1844. PMID: 27633186

Sponsor: Novo Nordisk A/S

Study Design: Randomized, parallel assignment, open label, enrolling 1201 participants

Intervention: Patients were randomly assigned (1:1:1:1) by use of an interactive web-response system to once a week treatment with either semaglutide 0.5 mg, dulaglutide 0.75 mg, semaglutide 1.0 mg, or dulaglutide 1.5 mg subcutaneously.

Primary Outcome Measure: Change in A1C at week 40

Secondary Outcome Measures:

  1. change in body weight (kg) at week 40;
  2. change in fasting plasma glucose at week 40;
  3. change in systolic and diastolic blood pressure at week 40;
  4. change in overall scores for Diabetes Treatment Satisfaction Questionnaire at week 40; and
  5. A1C below or equal to 6.5% at week 40.

Results: 1201 patients were randomized, with 94% completing the trial. The mean A1C change was compared between the low doses and high doses.

Low

High

Mean bodyweight change was compared between the low doses and the high doses.

Low

High

Summary: This study demonstrates that when directly comparing low and high doses of semaglutide to dulaglutide, the improvements in A1C and body weight are statistically significantly better with semaglutide, with similar safety profiles.

Semaglutide is the newest GLP-1 to become available to the U.S. market. These data suggest that we may be able to get patients with A1Cs of 8.5-8.8% to goal by adding semaglutide with a concomitant weight loss of at least 10 lbs.


Efficacy and Safety of Semaglutide Once-weekly versus Exenatide ER 2.0 mg Once-weekly as Add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects with Type 2 Diabetes (SUSTAIN™ 3 – versus QW GLP-1)

Study Title Acronym: SUSTAIN 3

ClinicalTrials.gov Identifier: NCT01885208

References (related):

  1. Ahmann, A., Capehorn, M., Charpentier, G., Dotta, F., Henkel, E., Lingvay, I., Holst, A., Annett, M. and Aroda, V. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. (2018). Diabetes Care, 41(2), pp.258-266. PMID: 29246950
  2. Semaglutide (Ozempic)–another injectable GLP-1 receptor agonist for type 2 diabetes. [No authors listed] Med Lett Drugs Ther. 2018 Jan 29;60(1539):19-21. PMID: 29364197
  3. Marso, S., Bain, S., Consoli, A., Eliaschewitz, F., Jódar, E., Leiter, L., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M., Woo, V., Hansen, O., Holst, A., Pettersson, J., Vilsbøll, T.; SUSTAIN-6 Investigators. (2018). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med, 375(19), pp.1834-1844. PMID: 27633186

Sponsor: Novo Nordisk A/S

Study Design: Randomized, parallel assignment, open label

Intervention: 1.0 mg semaglutide or 2.0 mg exenatide ER once weekly

Primary Outcome Measure: Change from baseline in A1C at week 56

Secondary Outcome Measures:

  1. change from baseline in body weight at week 56;
  2. change from baseline in fasting plasma glucose (FPG) at week 56;
  3. change from baseline in systolic and diastolic blood at week 56;
  4. change from baseline in Diabetes Treatment Satisfaction Questionnaire status (DTSQs) at week 56; and
  5. subjects who achieve A1C equal to or below 6.5% at week 56.

Results: In all, 813 participants were randomized to 56 weekly treatments of semaglutide or exenatide ER.

Mean baseline A1C of 8.3% was reduced by 1.5% with semaglutide and 0.9% with exenatide ER. The estimated treatment difference for semaglutide versus exenatide ER was -0.62% [95% CI -0.80, -0.44] P < 0.0001 for noninferiority and superiority). In all, 67% of the subjects treated with semaglutide achieved A1C <7.0% versus 40% of those taking exenatide ER.

Mean body weight of 95.8 kg at baseline was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER for an estimated treatment difference of  -3.78 kg [95% CI -4.58, -2.98]; P < 0.0001).

Summary: This study compared semaglutide directly with the once-weekly formulation of exenatide. It found that semaglutide at a dose of 1.0 mg weekly was superior to the current weekly exenatide ER dose (2.0 mg/week) at improving glycemic control and reducing body weight after 56 weeks of treatment. Safety profiles were similar between the two drugs.

This study provides more evidence of the efficacy of the newest GLP-1 and allows us to compare it to exenatide, which has been available in the U.S. since 2012. The 1.5% decrease in A1C shows that we could anticipate getting A1C to goal by adding semaglutide if a patient has an A1C of 8.5% or less on his or her current regimen.

Access additional resources and practical information to enhance the care and treatment of your diabetes patients.

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About our expert: Kathleen Wyne, MD, PhD, FACE, FNLA, Associate Professor, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Wexner Medical Center, Columbus

Endnotes:
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Source URL: https://www.diabetesselfmanagement.com/practical-diabetology/journal-watch/journal-watch-continuous-glucose-monitoring-and-risk-of-hypoglycemia/


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