Protocol V7 – First working protocol Approved by MREC - 26/10/07

Protocol V8 - Addition of new prefilled device for injection of Glargine. Approved by MREC 04/06/2008

Protocol V9 - Addition of new sites. Approved by MREC 16/02/09

Protocol version 10 - amended to no longer collect blood for HbA1c for central analysis. Correction of serum IGF1, IGFBP-3 instead of plasma. Removal of specifically named measure for waist circumferences. Addition of new sites plus removal of 2 sites. Re-submitted to MREC as Protocol 10.1

Protocol version 10.1 - Revised inclusion criteria - HbA1c increased to =/<12%. Approved by MREC 15/06/09

Protocol version 11 - Revision to eligibility criteria. The protocol has therefore been amended to facilitate recruitment and include girls who are in late puberty but have not yet attained menarche. Study timeline revised. List of participating sites was updated. Approved by MREC 02/12/09

Protocol V12 - revised to include additional information stating what will happen in the event of a positive pregnancy test. Approved by MREC 30/03/2010

Protocol version 13 - protocol revised to update study timeline, extending recruitment. Update of the list of participating centres. References to the measurement of HbA1c will allow for the change from % to mmol/mol which was coming into effect. The possibility of combining screening (randomisation) and baseline visits into one visit has been allowed for. The use of finger prick HbA1c measurement by some sites means that there is no longer a delay in assessing HbA1c eligibility criteria. The label template for the study drugs has been amended to include the text 'For Clinical Trial Use Only' Approved by MREC 28/09/2010

Protocol V14 - Revision of Protocol This includes the following:- •Text has been amended to allow for the use of email as well as, or instead of, telephone contact. Introduction of an email contact sheet •List of study sites has been updated – •Method of reporting HbA1C has been changed from DCCT to IFFC in line with recent changes. •Removal of Barry Widmer as Data manager (now left). •Change of text (from in to by) to allow for the possibility of future archiving being off site rather than within the department. • A Protocol section has been created to include information about sponsorship, finance and insurance. •Participant information sheets have been amendment to allow for email as a method of contact. •Consent and Assent forms have been updated to reflect changes to the information sheets. •Once participants have completed the study we would like to thank them for their help. We propose to send out a thank you letter and certificate of achievement. • We propose to send out a letter to participants GPs notifying them that they have now finished the study. Submitted to MREC only

Protocol V15 - Revision of Protocol. This includes the following: •Text amended throughout the protocol to allow for the exclusion of DEXA scan in centres where access is not available to appropriate facilities and /or software (paediatric) •Participant information sheets amended to allow for the exclusion of DEXA scans •Consent and Assent forms updated to reflect changes to the information sheets •Wording for consent forms amended in Clause 3 so there is uniformity across the forms and in line with ethical recommendations •Minor typo corrections – Primarily BMI SDS minimisation altered from ≤2.5 to < or ≥ 1, and > sign for other minimisation criteria corrected to ≥ •Dr Rachel Williams’ role as Co-ordinating Investigator has been recognised •Study time line extended. Submitted to MREC only

Protocol 16 - •In accordance with the protocol, a Data Monitoring committee has been convened and details listed in the appendix •Detail of a proposed Interim analysis •The list of study sites has been amended and updated •Typo correction to Power Calculation on Page 23 •Clarification that NOVO Nordisk will only be notified of SADR’s relating to their product (Detemir) • Appetite assessment forms will only be done at 3,6,9 & 12 month visits, Submitted to MREC only.

Protocol version 17 - Clarification regarding pregnancy reporting. Additional information defining the end of the study. Additional information relating to document management and archiving. Approved by MREC 04/05/2016