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Background: Attaining optimal glucose control in type 2 diabetes (T2DM) is essential to minimise complications, but difficult to achieve in practice with declining β-cell function in patients. Aim: To evaluate the efficacy and feasibility of a protocol-led, treat-to-target approach emphasising earlier oral hypoglycaemic agent (OHA) combination and insulin use to target basal and prandial glucose in primary care. Methods: T2DM patients aged 40-75 years, with glycosylated haemoglobin (HbA_1C) 6.4-10.0% on diet or oral monotherapy in 7 practices were asked to participate in a protocol-led, target-driven programme of care using early OHA and insulin therapy combinations to target basal and prandial glucose. Recruited patients were randomised to pre-specified algorithms with monthly therapy adjustment aiming for fasting plasma glucose values (FPG) <6mmol/L and 2-hour post-prandial (PPG) <8mmol/L. Isophane or humalog insulin was added where glucose targets were not attained. All patients were reviewed at one year. Glucose, weight and cardiovascular (CVS) risk factor outcomes were measured and the feasibility, acceptability and safety of the programme evaluated with validated questionnaires. Results: 345 patients were studied. 60 participated in the glucose study and 285 received standard care. 65% of recruited patients were male, with mean (SD) age 61.0 (8.2) years, BMI 29.8 (5.3) kg/m2, HbA_1C 7.5 (0.9)% and median (IQR) T2DM duration 3 (1-5) years. 41 completed the study. Glucose control was significantly improved in recruited compared to non-recruited patients with a mean overall 0.8% HbA_1C reduction and 72% patients achieving HbA_1C<7% and 64% <6.5% at 1 year. Therapy use was also significantly increased with 50% requiring 3 therapies, 30% 2 and 10% monotherapy. 24 (59%) of recruited patients received isophane and 16 (39%) humalog to achieve targets. Glucose optimisation was achieved without significant hypoglycaemia or adverse events and patient quality of life (QoL) and therapy satisfaction remained high. CVS risk was reduced in recruited patients. Conclusions: A more structured, target-driven approach to glucose optimisation can successfully achieve normoglycaemia in a selected primary care T2DM population without significant adverse events, hypoglycaemia. or QoL impairment in patients. A principal barrier to wider implementation of this programme appears to be practice and patient participation.