Author

M. Sharma

Abstract

One challenging prescribing decision in type 2 diabetes mellitus (T2DM) is when clinicians must choose between sitagliptin and sulphonylureas as add-on to metformin based on effectiveness. Evidence on effectiveness of sitagliptin versus sulphonylureas as add-on to metformin was therefore systematically searched and revealed no study evaluating "real-world" comparative effectiveness of these treatments, particularly in older, more comorbid individuals. To address this gap, The Health Improvement Network, UK primary care database was used to extract a cohort of 26,844 individuals with T2DM prescribed these treatments and four cohort studies were undertaken to evaluate their comparative effectiveness. The first two studies demonstrated no difference in HbA1c reduction, approximately 12 months after initiating either treatment as add-on to metformin, however a significant comparative weight reduction with sitagliptin in those aged 18-75 (-2.26kg 95%CI -2.48 to -2.04) and ≥75 (-1.31kg 95%CI -1.96 to -0.66) was found. Two further studies revealed individuals prescribed sitagliptin were 11% more likely to record an undesirable HbA1c >58mmol/mol (Hazard Ratio 1.11 95%CI 1.06-1.16), however nearly twice as likely to record an anti-diabetic treatment change (HR 1.98 95%CI 1.86-2.10) compared to sulphonylurea initiators. This analysis on treatment change also highlighted an underlying inertia in both groups, as 66.4% of those prescribed sitagliptin and 83.7% prescribed sulphonylureas had no treatment change introduced despite recording a HbA1c >58 mmol/mol. This thesis provides "real-world" evidence that both sitagliptin and sulphonylureas are equally effective in lowering HbA1c and achieving glycaemic targets in a population that includes individuals aged ≥75 and with significant comorbidity. Sitagliptin is preferable for weight reduction. There is however, a substantial inertia in changing treatment when targets are not met, which is greater among sulphonylurea initiators. There remains a need to eliminate barriers preventing clinicians changing treatment when these two add-on medications prove inadequate, and further evaluate their longer-term comparative effectiveness.