An observational study from Scotland has shown that dapagliflozin produced equivalent improvements in glycaemic control in patients with type 2 diabetes in general practice to those reported in clinical trials.

The Scottish Diabetes Research Network Epidemiology Group used data from the Scottish Care Information-Diabetes collaboration database, which links with mortality data from the General Registrar. Participants in the study were aged 18-80 years at entry with a diagnosis of type 2 diabetes. Dapagliflozin ever users were defined as patients with any initiation of dapagliflozin between November 2012, when the drug was introduced, and the end of the study.

In total, 8,566 dapagliflozin users, of whom 7,231 were considered ‘on licence’, and 230,310 never users met the inclusion criteria. Altogether there were 6,674 person-years of follow-up post initiation and median follow-up was 210 days. Dapagliflozin was most commonly used as a third-line add-on therapy.

Crude changes in the treatment group were adjusted because of the known tendency of HbA_1c to increase over time.

• The crude within-person change in HbA_1c was−10.41 mmol/mol (−0.95%) after 3 months’ exposure.

• The crude change after 12 months was −12.99 mmol/mol (−1.19%)

• However, when adjustment for the expected rise over time in HbA_1c was taken into consideration the dapagliflozin exposure effect estimate was −15.14 mmol/mol (95% CI:−15.87 to −14.41) i.e.−1.39% (95% CI: −1.45 to −1.32) at 12 months and this was maintained thereafter.

A drop in systolic blood pressure of −4.32 mmHg (95% CI: −4.84 to −3.79) on exposure within the first 3 months was also maintained.

Reductions in BMI and body weight stabilised by 6 months at −0.82 kg/m² (95% CI: −0.87 to −0.77) and −2.20 kg (95% CI: −2.34 to −2.06) and were maintained. eGFR declined initially by −1.81 ml/min/1.73 m² (95% CI: −2.10 to −1.52) at 3 months but varied thereafter.

There were no significant effects of cumulative drug exposure on safety outcomes, although the authors acknowledge the dataset was underpowered to detect these with confidence.

The investigators conclude: ‘The effectiveness of dapagliflozin on HbA_1c and other clinical outcomes observed in clinical trials was apparent in this real-world effectiveness study; treatment effect estimates were at least as large as in clinical trials even when likely observational analysis biases are considered. Dapagliflozin lowers HbA1c and SBP shortly after treatment initiation but also appears to prevent worsening of these outcomes over the ensuing 2 years. Dapagliflozin also lowered BMI and body weight.’

This study is interesting because it shows where most GPs currently place SGLT2 inhibitors as add-on therapy in type 2 diabetes. The data from real-world use mirror the data from clinical trials and seem to show safe reduction in HbA_1c and other cardiovascular risk factors. Most clinicians are encouraged that weight loss with an SGLT2 inhibitor can help to bolster lifestyle changes.

Dr Matthew Lockyer