function, current conservative approach may not be sufficient and an approach to ‘treat-to-target’ may be required. In suitable newly diagnosed patients, a combination therapy to start with may be the optimum approach. The concept of ‘legacy effect’ also suggests that early combination therapy may create a ‘good legacy’ in T2DM patients, which can help over long duration in terms of lesser complications.

Starting with a combination therapy should also include the evaluation of medications. Ideally, the ones with synergistic or complimentary actions should be preferred. It should also be taken into account whether the medications are addressing the key pathophysiology or merely addressing the symptoms. The ones acting on insulin resistance as well as sustaining b-cell function can help the patients over long-term. There is emerging real-world evidence in terms of multi-country INITIAL study on early intensification, where patients were given vildagliptin+metformin to start with. Upcoming studies like GRADE and VERIFY have the potential to provide invaluable insights on benefits of starting with a combination therapy, including durability of b cells over long-term.