SGLT-2-remmers: glucosurie als diabetesbehandeling

Objective The Sodium Glucose co-Transporter 2 (SGLT-2) is responsible for the reabsorption of the filtered glucose in the proximal tubule. Inhibiting SGLT-2 increases glucosuria which could potentially be a new treatment option for patients with type 2 diabetes. This study describes the efficacy and safety of the SGLT-2 inhibitor dapagliflozin, registered in the Netherlands for treatment of type 2 diabetes mellitus. Design: Literature study. Method: The Medline database was searched up to and including 19 October 2012 for systematic reviews and randomised trials with a minimum duration of 12 weeks in patients with DM2. Two authors independently selected the studies based on the title, abstract and, if necessary, the full text. From selected studies, information about design (randomisation, control group (placebo group) and blinding), population (co-morbidity, number of patients), intervention (duration and dose) and results (HbA1c, adverse events, quality of life, bodyweight, micro- en macrovascular complications en mortality) was gathered. Results: In addition to 3 systematic reviews, 11 studies on dapagliflozin were included. The mean age in the different studies was relatively low (51-61 years) and mean HbA1c at baseline was between 7.7-8.5% (61-69 mmol/mol). According to these studies, dapagliflozin gave a mean HbA1c reduction of 0.5-0.8% (6-9 mmol/mol). Dapagliflozin was associated with a 1.0-2.4 kg weight loss compared to placebo and/or metformin. Urinary tract and genital infections occurred two and three to four times more often, respectively. Data on microvascular and macrovascular complications, as well as data on mortality, are not yet available for dapagliflozin. Conclusion: Dapagliflozin regulates blood glucose levels less effectively than the current glucose-lowering agents, although in the few trials comparing dapagliflozin with metformin and glipizide, no difference in HbA1c was found, and gives only moderate bodyweight reduction. A recent systematic review concluded that the HbA1c decrease caused by dapagliflozin was 0.52% (6 mmol/mol) (95% confidence interval: 0.46-0.57% (5-6 mmol/mol)). Data on efficacy and safety in the long term are not yet available.