Efficacy and safety of using insulin glargine 300 U/mL in patients on advanced insulin therapy with type 1 or type 2 diabetes failing to achieve their glycemic targets. The Toujeo-Neo trial.

ISRCTN	ISRCTN93674355
DOI	https://doi.org/10.1186/ISRCTN93674355
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	GLARGL07591
Sponsor	Sanofi-Aventis Deutschland GmbH
Funder	Sanofi-Aventis Deutschland GmbH

Submission date: 26/02/2019
Registration date: 27/02/2019
Last edited: 27/09/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
All people with diabetes need insulin, either directly after diagnosis in patients with type 1 diabetes or at later disease stages in people with type 2 diabetes. There are two kind of insulin available to imitate the body’s missing insulin supply: basal insulin to cover the basal need for insulin and mealtime insulin to cover the shortly elevated need after meal intake. Advanced insulin therapies using one or two shots of mealtime insulin together with basal insulin are used in long-lasting type 2 diabetes and therapies with three shots of mealtime insulin are used in long-lasting type 2 diabetes as well as in type 1 diabetes. To take insulin goes hand in hand with hypoglycemia, an unwanted state of too low blood sugar with several symptoms, sometimes even including fainting and coma. Therefore, fear of hypoglycemia often prevents people with diabetes to achieve their blood sugar targets. On the other hand it is very important for patients with diabetes to reach their blood sugar targets to avoid late-stage complications like kidney disease, eye disorders and cardiovascular diseases. Several newer types of insulins have been developed, which reduce the risk for hypoglycemia compared to older types of insulin. The aim of this study is to find out, if switching from any other basal insulin to insulin glargine 300 units per milliliter, a newer basal insulin, allows more people with type 1 or type 2 diabetes on advanced insulin therapies (using a basal and a mealtime insulin) to reach their blood sugar targets without increasing the risk of hypoglycemia in daily clinical practice.

Who can participate?
Adults at or over the age of 18 years with type 1 or type 2 diabetes who use advanced insulin therapies (basal and mealtime insulin) and are treated by a German physician.

What does the study involve?
Participants are elected by their treating physician to join this study, if the physician had already decided to switch their basal insulin to insulin glargine 300 units per milliliter independent of the participation in this study. Participants will be treated by their physician as usual and will visit their doctor in the usual time intervals (in Germany usually every three months for diabetes patients). The physician will document several parameters at the first visit, when the basal insulin is switched, and at least 6 and 12 months thereafter. The study lasts one year in total. The participants are asked to answer a diabetes treatment satisfaction questionnaire at the first visit and at the visit 12 months thereafter.

What are the possible benefits and risks of participating?
There will be no immediate direct benefit or risk to those taking part, because this is a non-interventional study which means that patients are treated as they would be without participation in this study. However, the results of this study will add to the knowledge of how insulin glargine 300 units per milliliter is used in daily clinical practice and how its use in combination with mealtime insulins can be improved.

Where is the study run from?
The Toujeo-Neo study is being run by Sanofi-Aventis Deutschland GmbH and takes place in diabetologists’ and general practioners’, family physicians’ and internists’ practices all over Germany, where people with type 1 and type 2 diabetes are treated.

When is the study starting and now long is it expected to run for?
August 2015 to March 2017

Who is funding the study?
Sanofi-Aventis Deutschland GmbH (Germany)

Who is the main contact?
Dr. Stefan Pscherer, chief physician of Clinic of Internal Medicine III, Diabetology and Nephrology, Sophien- und Hufeland-Klinikum gGmbH, Henry-van-de-Velde-Str. 2, D-99425 Weimar, Germany, email: S.Pscherer@klinikum-weimar.de

Contact information

Dr Katrin Pegelow
Scientific

Sanofi-Aventis Deutschland GmbH
Potsdamer Str. 8
Berlin
D-10785
Germany

Phone	+49 (0)30 2575 2920
Email	Katrin.Pegelow@sanofi.com

Study information

Primary study design	Observational
Study design	Non-interventional open-label multi-center single-arm prospective observational study
Secondary study design	Longitudinal study
Study type	Participant information sheet
Scientific title	Assessment of Treatment Efficacy and Safety when switching the Basal component of any BOTplus or Basal-Bolus Regimen in Patients Failing to Reach Treatment Targets to Insulin glargine U300
Study acronym	Toujeo-Neo
Study objectives	The aim of this non-interventional study (NIS) was to document the treatment effectiveness and safety after 6 and 12 months for diabetes patients who switched from a basal Insulin supported oral therapy with additional 1-2 prandial Insulin injections (BOTplus; type 2 diabetes mellitus) or a basal-bolus therapy (BBT; type 1 or type 2 diabetes mellitus; T1DM, T2DM) with any basal insulin other than insulin glargine 300 U/mL to a BOTplus or BBT with insulin glargine 300 U/mL under use in real-life conditions in daily clinical practice.
Ethics approval(s)	Approved 27/07/2015, Ethik-Kommission der Bayerischen Landesärztekammer/Ethical committee of the state medical council of Bavaria (Mühlbaurstr.16, D-81677, Munich; + 49 89 4147-165; ethikkommission@blaek.de), ref: 15049
Health condition(s) or problem(s) studied	Type 1 and type 2 diabetes mellitus in adult patients requiring insulin therapy.
Intervention	All data were collected three times: at baseline, approximately 6 and approximately 12 months after starting insulin glargine 300 U/mL therapy. Baseline documentation (documentation 1) had to start immediately after switching to insulin glargine 300 U/mL from any other basal insulin after failing to achieve the glycemic targets on a pre-existing BOTplus (T2DM) or BBT (T1DM and T2DM) treatment. This had to occur after the physician had independently of the participation in this study decided to prescribe insulin glargine 300 U/mL and when thereafter the physician and the patient had decided the participation of the latter in this study. Next measurements were documented approximately 6 months thereafter (documentation 2) and the last measurements were documented approximately 12 months thereafter (documentation 3). Besides this, all FBG measurements available were collected on a monthly basis asking for documentation of changes during the last four weeks each month. Also, dosing information was captured every month; i.e. actual dose and frequency of dose changes during the last four weeks. Data had to be generated during the daily clinical routine of the physicians. Any change in the patient’s antidiabetic therapy regimen was strictly left at the physician’s discretion. No therapeutic decision of the physician should have been based upon participation in this NIS. Titration algorithm was also left at the investigator’s discretion. Participating physicians were distributed equally all over Germany to allow for a representative sample of German T1DM and T2DM patients switching their basal insulin component of their BOTplus or BBT regimen. In order to allow for a valid statistical analysis even in smaller subgroups of patients (as distribution within the predefined subgroups may not be equal), it was planned to document and analyze about 2,500 patients. The planned number of participating sites was 540. Participating doctors were mostly to be diabetologists, as the kind of physician who usually follow-up basal plus prandial insulin therapy in T1DM and T2DM patients in Germany. Also, general practitioners, family physicians and internists (office based) were to be included in the study, if they treat advanced T2DM and T1DM patients. The practices were to be distributed equally all over Germany to allow for geographical representativeness.
Intervention type	Other
Primary outcome measure(s)	Duration (persistency) of response defined as time from start of response to end of response. Beginning of response was defined by time of the first of at least two FBG values below or equal to 110 mg/dL or time of first HbA1c below or equal to predefined individual target value whichever occurred first. End of response was defined as one of the following: - the second FBG value >110 mg/dL (>6.1 mmol/L) after start of FBG response or - the first HbA1c value above the individual predefined target or - change to another form of insulin therapy or change of basal insulin.
Key secondary outcome measure(s)	1. Absolute change in HbA1c from baseline to 6 months to 12 months 2. Absolute change in FBG from baseline to 6 months to 12 months 3. Response rate 6 and 12 months after start of insulin glargine 300 U/mL treatment defined by: - Reaching two FBG values below or equal to 110 mg/dL or at least once the predefined individual HbA1c target value or - Reaching at least one HbA1c value equal or less to the predefined individual HbA1c target value OR - Reaching two FBG values below or equal to 110 mg/dL or - Reaching two FBG values below or equal to 110 mg/dL and at least once the predefined individual HbA1c target value. 4. Time from start of insulin glargine 300 U/mL treatment to response for each of the response endpoints 5. Incidence rates and rates per patient-year were calculated for symptomatic, confirmed symptomatic, nocturnal, severe, and severe nocturnal hypoglycemia as reported in the electronic Case Report Form (eCRF). Confirmation of symptomatic hypoglycemia was defined as self-measured blood glucose (SMBG) measurement below or equal to 70 mg/dL. Severe hypoglycemia was defined as necessity of the assistance of another person or an SMBG measurement of below or equal to 56 mg/dL. Nocturnal hypoglycemia occurring during the night (approximately 10pm-6am), while the patient was asleep (symptomatic or confirmed by SMBG measurement below or equal to 70 mg/dL). Severe nocturnal hypoglycemia was defined as those nocturnal hypoglycemia fulfilling the Definition of severe hypoglycemia. 95% CIs for incidence rates were calculated according to Clopper-Pearson. Rates per patient-year were calculated as a cumulative number of hypoglycemia events for all patients divided by the cumulative duration of insulin glargine 300 U/mL therapy in years, whereas patients with missing treatment duration or missing number of hypoglycemic events were excluded. 6. Absolute change in the 4-point blood glucose profile from baseline to 6 months to 12 months 7. Absolute change in body weight from baseline to 6 months to 12 months 8. Absolute change in daily insulin doses (number of units and number of units per kg body weight [BW]) and number of dose modifications per visit. 9. Values and absolute changes for blood lipids (triglycerides, high-density Lipoprotein [HDL], low-density Lipoprotein [LDL] and total cholesterol) from baseline to 6 months to 12 months 10. Type of LLT overall and by LDL subgroups (<70 mg/dL, <100 mg/dL, 100-190 mg/dL, >190 mg/dL at respective visit). An intensification of LLT was defined as administration of an additional LLT drug compared to baseline, or a higher dosing of statin, i.e. change from moderate at one visit to intensive at a following visit. 11. Patient’s treatment satisfaction, measured by using the Diabetes Treatment Satisfaction Questionnaire (DTSQs) instrument is comprised of eight items. For scoring, six of these items were summed to produce a measure of satisfaction with treatment. The remaining two items (perceived frequency of hyperglycemia and perceived frequency of hypoglycemia) were treated individually. Measured at baseline, 6 months, and 12 months. 12. Safety parameters were incidences of adverse events (AE), related AEs, serious adverse events (SAE), related SAEs and fatal AEs.
Completion date	29/03/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	2500
Key inclusion criteria	1. Patients with type 1 diabetes (basal-bolus insulin therapy) or type 2 diabetes (basal insulin plus 1-2x prandial insulin and oral antidiabetic drugs or basal-bolus insulin therapy) with any basal insulin except insulin glargine 300 U/mL. 2. Adults and Seniors: Age at least 18 years, no upper age limit. 3. HbA1c between 7.5% to 10.0%. 4. Fasting blood glucose > 130 mg/dL. 5. Ability and willingness to perform blood glucose self-monitoring.
Key exclusion criteria	1. Contraindications for a therapy with insulin glargine 300 U/mL. 2. Patients receiving oral antidiabetic drug therapy only. 3. Patients receiving basal insulin and oral antidiabetic drugs without prandial insulin. 4. Patients with known cancer disease. 5. Pregnancy. 6. Drug or alcohol abuse. 7. Dementia or general incapacity to understand the content of the observational study.
Date of first enrolment	11/08/2015
Date of final enrolment	31/01/2016

Locations

Countries of recruitment

Germany

Study participating centres

Herr Dr. Stefan Pscherer

99425
Germany

Herr Dr. Frank Ackermann

06108
Germany

Frau Dr. Susanne Adler

33332
Germany

Herr Dr. Hasan Alawi

66740
Germany

Herr Dr. Heiko Ambrosch

06712
Germany

Frau Dr. Steffi Appelt

97421
Germany

Frau Dr. Kathrin Auerbach

04779
Germany

Herr Modjtaba Barghi

12347
Germany

Herr Jürgen Bartlewski

76139
Germany

Frau Dr. Anna Bartnik‐Mikuta

92237
Germany

Herr Dr. Bert Basan

18209
Germany

Herr Dr. Bernd Becker

45355
Germany

Herr Dr. Sven Becker

99085
Germany

Frau Dr. Kerstin Benecke

39104
Germany

Herr Dr. Matthias Benecke

06122
Germany

Herr Dr. Dirk Berger

31139
Germany

Herr Dr. Peter Berndt

45309
Germany

Herr Dr. Tasso Bieler

01587
Germany

Herr Dr. Ralph Achim Bierwirth

45138
Germany

Herr Igor Bolsun

89073
Germany

Herr Dr. Beqir Brahimi

47906
Germany

Herr Dr. Markus Braun

84489
Germany

Frau Dr. Daniela Brugger

83278
Germany

Herr Dr. Peter Bühler

88430
Germany

Herr Dr. Thomas Bulang

02625
Germany

Herr Dr. Klaus Burkhardt

91781
Germany

Herr Dr. Ronny Casneuf

30880
Germany

Frau Regina‐Monika Chmielewski

58675
Germany

Frau Maren Dehne

23879
Germany

Frau Dr. Iris Donati‐Hirsch

44137
Germany

Herr Dr. Markus Eidenmüller

35037
Germany

Herr Dr. Volker Eissing

26871
Germany

Frau Dr. Annette Engelhardt

99610
Germany

Frau Dr. Friedlinde Ernst

87439
Germany

Herr Dr. Franz‐Rudolf Fendler

30171
Germany

Frau Manuela Fettig‐Killat

76661
Germany

Herr Dr. Albrecht Fießelmann

13597
Germany

Herr Dr. Ulrich Flintzer

17033
Germany

Herr Frank Franzmann

32549
Germany

Frau Dr. Verena Fuhrmann

07545
Germany

Herr Dr. Alexander Garcia Godelmann

55130
Germany

Herr Dr. Gregor Gauer

01612
Germany

Frau Sonja Gericke

19348
Germany

Herr Dr. Peter Geßner

76149
Germany

Herr Dr. Sebastian Glüer‐Fuchs

30900
Germany

Herr Dr. Rainer‐Christian Görne

67433
Germany

Herr Kai Götte

61381
Germany

Herr Dr. Detlef Götze

39120
Germany

Herr Volkart Güntsch

19057
Germany

Herr Dirk Haaser

01309
Germany

Herr Andreas Hain

36266
Germany

Herr Dr. Peter Hainzinger

85057
Germany

Herr Dr. Dirk Hennig

01662
Germany

Frau Dr. Kerstin Herrmann‐Benecke

06122
Germany

Herr Dr. Joachim Hesse

19370
Germany

Herr Dr. Christoph Heyer

41747
Germany

Frau Dr. Henrike Hilbig

30165
Germany

Herr Dr. Roger Hladik

67063
Germany

Herr Dr. Hans‐Dieter Hoffmann

58706
Germany

Herr Dr. Gerd Hollmann

13439
Germany

Frau Susanne Höltz‐Röhrig

55624
Germany

Frau Dr. Birgit Höne‐Römmer

04299
Germany

Frau Dr. Irina Hort

10318
Germany

Herr Christoph Hummel

33602
Germany

Herr Dr. Michael Karl Huptas

45307
Germany

Herr Dr. Sebastian Huptas

45307
Germany

Herr Clemens Huth

47929
Germany

Herr Professor Dr. Hans‐Dieter Janisch

91052
Germany

Herr Dr. Hans‐Joachim Jonderko

76135
Germany

Herr Dr. Hans‐Peter Kempe

67059
Germany

Herr Professor Dr. Werner Kern

89073
Germany

Frau Dr. Stephanie Kieu

26388
Germany

Herr Dr. Andreas Kirsten

01129
Germany

Herr Dr. Gerhard Klausmann

63739
Germany

Herr Dr. Carsten Klugewitz

45277
Germany

Herr Dr. Karsten Knöbel

94315
Germany

Frau Dr. Nicole Koch

22041
Germany

Herr Dr. Thorsten Koch

22041
Germany

Herr Andreas Kochan

02826
Germany

Herr Dr. Wolfgang Kohn

13086
Germany

Frau Dr. Kerstin König

59174
Germany

Herr Dr. Günter Kraus

96117
Germany

Frau Katrin Krause

06366
Germany

Frau Irmhild Krüger

16928
Germany

Frau Dr. Kerstin Kux

49124
Germany

Herr Dr. Benedict Lacner

45468
Germany

Herr Dr. Bernhard Landers

56727
Germany

Herr Dr. Jürgen Landschulze

07768
Germany

Frau Dr. Vera Lang

91207
Germany

Herr Hendrik Lange

07570
Germany

Herr Dr. Harald Letterer

29459
Germany

Herr Privatdozent Dr. Ulrich Lotze

06556
Germany

Frau Dr. Jenny Luong‐Thanh

26388
Germany

Herr Dr. Lam Luong‐Thanh

26388
Germany

Frau Dr. Cornelia Marck

35415
Germany

Herr Dr. Ekkehard Martin

38165
Germany

Herr Dr. Peter Mayr

78333
Germany

Herr Dr. Claus Mees

67063
Germany

Frau Dr. Martina Meier‐Höfig

24796
Germany

Frau Peggy Meyer

13086
Germany

Herr Francesco Michelini

41472
Germany

Herr Dr. Uwe Milbradt

39387
Germany

Herr Dr. Rainer Möllmann

47799
Germany

Herr Dr. Joachim Müller

97421
Germany

Frau Gabriele Müller‐Hunold

38368
Germany

Herr Dr. Axel Müllhofer

88400
Germany

Frau Dr. Manuela Nader

82110
Germany

Herr Dr. Rainer Naus

87435
Germany

Herr Dr. Olaf Ney

31535
Germany

Herr Michael Nowotny

02763
Germany

Frau Dr. Katrin Ohde

45329
Germany

Herr Dr. Tobias Ohde

45329
Germany

Frau Dr. Silke Otto‐Hagemann

49377
Germany

Herr Dr. Andreas Patzelt

44892
Germany

Herr Dr. Johannes Peters

50126
Germany

Herr Dr. Gert Pfundt

55130
Germany

Herr Dr. Eberhard Politz

38518
Germany

Frau Maria Pollok

58675
Germany

Frau Stefanie Rasfeld

98574
Germany

Herr Björn Reißmann

58730
Germany

Frau Dr. Uta Rieger

14482
Germany

Herr Dr. Uwe Ritzel

26384
Germany

Herr Dr. Tobias Rückert

30165
Germany

Frau Dr. Emilia Ruff

97980
Germany

Frau Dr. Ursula Ruthe

14532
Germany

Herr Dr. Oliver Sauer

02826
Germany

Frau Dr. Astrid Sawistowsky

04249
Germany

Herr Dr. Jörg Schaper

86470
Germany

Herr Privatdozent Dr. Stephan Scharla

83435
Germany

Herr Edgar Schaubert

52457
Germany

Herr Dr. Thomas Schaum

23758
Germany

Herr Dr. Reinhard Schaupp

97762
Germany

Herr Dr. Martin Scherwinski

10823
Germany

Herr Alois Schießl

22041
Germany

Herr Dr. Joachim Schiwietz

49808
Germany

Herr Dr. Uwe Schläfer

87439
Germany

Herr Oliver Schlott

50126
Germany

Herr Heiko Schneider

99510
Germany

Frau Dr. Stefanie Schrader

30165
Germany

Frau Dr. Sabine Schulze

35043
Germany

Herr Toralf Schwarz

04442
Germany

Herr Dr. Andreas Schwittay

04564
Germany

Frau Dr. Kathrin Seuß

95032
Germany

Herr Dr. Andreas Staudenmeyer

49808
Germany

Herr Dr. Jörg Steindorf

04435
Germany

Frau Dorothea Stottmeister

39307
Germany

Herr Dr. Kai Straßmann

42699
Germany

Frau Dr. Eva‐Maria Streck

04643
Germany

Herr Matthias Strickling

46284
Germany

Frau Dr. Danuta Stryjek‐Kaminska

65185
Germany

Herr Dr. Werner Stürmer

97080
Germany

Herr Dr. Jörg Tafel

61350
Germany

Frau Dr. Birgit Teubner

03046
Germany

Herr Jörg Thelen

15806
Germany

Frau Svetlana Tlechas‐Tkatsch

14480
Germany

Herr Thomas Voigt

04654
Germany

Herr Wolf Heinrich von Aufseß

95445
Germany

Frau Dr. Heike Wagner

47829
Germany

Frau Ina Walter

99974
Germany

Frau Dr. Daniela Walther

67246
Germany

Frau Ingrid Weber

26725
Germany

Herr Dr. Norbert Weghmann

52066
Germany

Herr Dr. Rolf Weißmann

90411
Germany

Herr Dr. Artur Zimmermann

83043
Germany

Herr Dr. Stefan Zinn

36341
Germany

Herr Dr. Jens Abendroth

06188
Germany

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results	Pscherer S, Fritsche A, Anderten H, Pegelow K, Seufert J, Pfohl M. Switching to Insulin Glargine 0 U/mL (Gla-0) after Failure of Advanced Insulin Therapy (IT) with Other Basal Insulins (BI) in Patients (Pts) with Type 2 Diabetes (T2DM) Improved Glycemic Control. Diabetes 2018; 67 (Suppl. 1): Abstract 2288-PUB (Published only). Available at:	23/06/2018		No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Poster results	Pscherer S, Pfohl M, Anderten H, Pegelow K, Seufert J. Nicht-interventionelle Studie zur Untersuchung der Effizienz des Wechsels der Basalinsulinkomponente bei einer BOTplus oder intensivierten Insulintherapie (ICT) zu Insulin glargin 0 E/ml bei Typ-1- und Typ-2-Diabetespatienten mit inadäquater glykämischer Kontrolle. Diabetologie & Stoffwechsel 2016; 11 (Suppl. 1): Abstr. P220. Presented as poster at the 51rst Annual Meeting of the German Diabetes Association (DDG) at 05.05.2016 in Berlin, Germany. Available at:	05/05/2016		No	No
Poster results	Fritsche A, Pscherer S, Pfohl M, Anderten H, Pegelow K, Seufert J. Umstellung des Basalinsulins auf Insulin glargin 0 E/ml (Gla-0) nach Versagen der Basis-Bolus-Therapie (ICT) mit einem anderen Basalinsulin verbesserte bei Typ-1-Diabetespatienten die Blutzucker-Einstellung – 6-Monats-Ergebnisse der Toujeo-Neo-T1DM-Studie. Diabetologie & Stoffwechsel 2018; 13 (Suppl. 1): S61, Abstract P181. Presented as poster at the 53rst Annual Meeting of the German Diabetes Association (DDG) at 11.05.2018 in Berlin, Germany. Available at:	11/05/2018		No	No
Poster results	Pscherer S, Pfohl M, Fritsche A, Anderten H, Pegelow K, Seufert J. Umstellung des Basalinsulins auf Insulin glargin 0 E/ml (Gla-0) nach Versagen einer Basis-Bolus- (ICT) oder einer basalunterstützten oralen Therapie mit einmal täglich prandialem Insulin (BOTplus) mit einem anderen Basalinsulin verbesserte bei Typ-2-Diabetespatienten die glykämische Kontrolle – 6-Monats-Ergebnisse der Toujeo-Neo-T2DM-Studie. Diabetologie & Stoffwechsel 2018; 13 (Suppl. 1): S51-S52, Abstract P153. Presented as poster at the 53rst Annual Meeting of the German Diabetes Association (DDG) at 11.05.2018 in Berlin, Germany. Available at:	11/05/2018		No	No
Poster results	Fritsche A, Pscherer S, Anderten H, Pegelow K, Seufert J, Pfohl M. Switching to Insulin Glargine 0 U/mL (Gla-0) Improves Glycemic Control After Failure of Basal-Bolus Therapy (BBT) With Other Basal Insulins (BI) in patients (pts) with Type 1 Diabetes (T1DM). Diabetes 2018; 67 (Suppl. 1): Abstract 1031-P. Presented as poster at the 78th Scientific Sessions of the American Diabetes Association at 23.06.2018 in Orlando, FL, USA. Available at:	23/06/2018		No	No
Protocol file	version 1.0	06/05/2015	27/09/2022	No	No

Additional files

ISRCTN93674355 Protocol v1.0 06May2015.pdf: Protocol file

Editorial Notes

27/09/2022: Uploaded protocol (not peer-reviewed) as an additional file.
27/02/2019: Trial’s existence confirmed by IRB