From efficacy to effectiveness in treatment of type 2 diabetes mellitus: Making the transition

Talk Code: 
Manuj Sharma
Prof Irwin Nazareth(IN), Dr Irene Petersen (IP)
Author institutions: 
MS, IN, IP all affiliated to University College London, London, UK, IP also affiliated to Aarhus University, Aarhus, Denmark


Individuals who enter randomized controlled trials (RCT) for type 2 diabetes mellitus (T2DM) often differ from individuals treated in the “real world”. To evaluate effectiveness of a drug in a “real world” population it is important to understand on what characteristics the two samples differ.


We identified a cohort of primary care patients with T2DM prescribed sitagliptin or a sulphonylurea as add-on to metformin in The Health Improvement Network (THIN) primary care database. We then compared their baseline characteristics at add-on treatment initiation to that of the largest RCT study population available considering the same clinical scenario.


We identified 5,728 patients prescribed sitagliptin and 42,610 prescribed a sulphonylurea as add-on to metformin in THIN compared to 588 on sitagliptin and 584 on a sulphonylurea in the equivalent RCT. Our “real-world” population initiated on sitagliptin had a similar proportion of males: 3,397 (59.3%) vs 336 (57.1%) in the RCT; a higher baseline weight: 99.1kg (Standard Deviation (SD) 22.3) vs 89.5 (SD 17.4) in the RCT; a shorter history of diabetes: 4.9 years (SD 4.1) vs 6.5 (SD 6.1) and higher baseline HbA1c: 8.7% (SD 1.4) vs 7.7% ( SD 0.9) in the RCT. The “real world” cohort initiated on sulphonylurea had a similar proportion of males: 24,945 (58.5%) vs 358 (61.3%) in the RCT, similar baseline weight: 90.4kg (SD 20.3) vs 89.7 (SD 17.5); a shorter history of diabetes (4.9 years (SD 4.0) vs 6.2 (SD 5.4)) and marginally higher baseline HbA1c 8.0% (SD 1.7) vs 7.6%( SD 0.9) in the RCT. Age was similar at baseline between the “real world” and RCT patient cohorts for both treatments. Missing data among the “real world” patients was highest for baseline body weight for both sitagliptin (13.7%) and sulphonylurea (20.6%).


Our study suggests that individuals who received sitagliptin or sulphonylurea treatment as add-on initiated it earlier than in the RCT and had worse baseline HbA1c control. Sitagliptin “real world” patients were also heavier at initiation (where weight was recorded). Such factors should be taken into consideration when evaluating treatments in primary care and to understand why effectiveness may differ from efficacy.

Submitted by: 
Manuj Sharma
Funding acknowledgement: 
This work has been supported by a grant from Novo Nordisk A/S. The views expressed are those of the authors and do not necessarily represent those of Novo Nordisk A/S.