Improving Glucose Outcomes Using a Novel Treatment Strategy in Young Adult Onset Type 2 Diabetes

After baseline tests are performed, subjects will be randomised to either a continuous glucose monitoring (CGM) guided, rapid titration of treatment strategy or a currently accepted standard of care type 2 diabetes treatment strategy. Treatment strategies (both rapid titration and standard of care) will be managed by experienced Endocrinologists for the duration of the study period. Rapid Titration Treatment Strategy: During the initial (six week) phase of the study, participants randomised to the rapid titration treatment strategy will be seen weekly for assessment and possible intensification of treatment. Weekly CGM recordings will be used to guide treatment decisions and assessments will be made on the basis of the mean blood glucose level (MBG). A MBG of 7.56 mmol/l has been found to correlate with an HbA1c of 6.5% (Nathan DM et al. Diabetologia 2007; 50: 2239-2244). If the MBG during the final 48 hours of the weekly recording is >7.56 mmol/l, treatment will be intensified. Treatment will begin with metformin (titrated from 1 g daily to 2 g daily) followed by the addition of an SGLT2 inhibitor (empagliflozin - 10 mg daily titrated to 25 mg daily) and then GLP-1 receptor agonist (liraglutide - 0.6 mg daily titrated to a maximum of 1.8 mg daily) in sequential addition. In the event that a participant is intolerant of metformin, treatment will progress to the next agent in the algorithm, empaglifozin. If treatment with the GLP-1 receptor agonist is required it will be commenced at the starting dose as per product information. The dose will be up-titrated according to recommendations within the product information provided by the manufacturer. If a higher dose of medication is not tolerated then reversion will be to the maximum tolerated dose. At the end of the rapid titration period, participants should be at the target MBG level and/or on the maximum tolerated combination of metformin, empagliflozin and liraglutide. Participants continue on their treatment regimen established by week 6 and are seen again after 3 months of treatment. From this point on, further treatment intensification will be based on achieving an HbA1c target of <6.5%. The active treatment phase of this trial will last twelve months. In addition to the assessment performed after 3 months, participants will also seen after 6 months and 9 months and treatment will be intensified if the HbA1c is not at the target level (<6.5%). If the HbA1c target of <6.5% is not achieved or maintained on combination therapy with metformin, empagliflozin and liraglutide, insulin can be commenced. An on insulin HbA1c target of <7% without hypoglycaemia will be applied. This is consistent with the current Australian Diabetes Society endorsed clinical guidelines. To ensure treatment fidelity, primary care physicians will be contacted by the investigator team prior to randomisation requesting that on-study treatment be left unchanged except in the case of a severe adverse event. A 24 hour emergency contact number will be provided to assist. In addition all participants will be provided with a trial summary card including the emergency contact number. Treatment retention will be facilitated by the provision of a flexible appointment schedule and provisions will be made to ensure ease of access to Royal Prince Alfred Hospital on an individual basis.