Dr Urvi Desai Analysis Group Inc, Boston, MA

| 19 March 2019

Standard treatment guidelines for type 2 diabetes call for starting with a single type of treatment (monotherapy) to lower and maintain healthy blood glucose levels. The most common oral medication used as a monotherapy is either metformin or a sulfonylurea. If, after 3 months, there is evidence that the monotherapy is not helping to achieve glycemic control (typically defined as HbA1c <7% [or 53 mmol/mol]), treatment can be intensified with the addition of other oral or injectable medications.

In common practice, however, there is little consistency in the interval between the initial indication of monotherapy failure and the intensification of treatment. In fact, real-world evidence indicates that, all too often, there is an extended delay before people with type 2 diabetes receive intensified treatment (also known as “clinical inertia”), even when glucose levels remain elevated. In our own study (, we found that three quarters of adults with type 2 diabetes in the UK do not receive intensified treatment for more than 12 months after initial indications of monotherapy failure. In fact, 44% of the patients in our study did not have any indication of treatment intensification whatsoever for up to five years following monotherapy failure. This gap can be harmful to patients, since the lack of adequate glycemic control could result in other serious health complications.

To develop insights into the impact of delayed treatment intensification on subsequent glycemic outcomes, we conducted a retrospective cohort study of adults with type 2 diabetes, using data from the UK’s Clinical Practice Research Datalink (CPRD). We found that, when it comes to achieving and maintaining glycemic control (i.e. HbA1c <7%), the earlier the intensified treatments are introduced, the better the patient’s response is likely to be.

We analyzed three cohorts: 1) early intensifiers, whose treatment was intensified within 12 months of the index (monotherapy failure) date; 2) intermediate intensifiers, with treatment intensifying 12 to 24 months after the index date; and 3) late intensifiers, with treatment intensifying 24 to 36 months after the index date.

Among our results was the finding that, during the period after intensification, the proportion of those achieving glycemic control was higher for earlier intensifiers (66%) than for intermediate (63%) and late (62%) intensifiers. In addition, the median time from intensification to attainment of control was approximately six months shorter among early intensifiers than among late intensifiers. Furthermore, earlier intensifiers were more likely to maintain the lower glycemic levels than the late intensifiers. This means that, on average, early intensifiers were exposed for shorter periods of time to the more harmful effects of high blood glucose levels.

Our findings may prompt a renewed call to action for both people with type 2 diabetes and their health care providers. Several studies have noted that both patients and their healthcare providers often have negative perceptions towards intensifying treatment, which could be a contributing factor to the delayed intensification patterns found in the real world. However, our study findings indicate that earlier intensification may provide an opportunity, not only to improve the likelihood of attaining desired glucose levels, but also to do so sooner, and maintain these levels for longer periods of time. This, in turn, can potentially reduce the risk of developing diabetes-related complications in the future, although this is an area that calls for further research. People with type 2 diabetes and their healthcare providers should consider discussing the potential benefits of intensified treatment early on in the treatment paradigm, and make the necessary adjustments in a timely manner.

Urvi Desai PhD, Analysis Group, Inc., Boston, MA.