A study to assess effectiveness of drug treatment and its effect on heart safety of patients taking dapagliflozin (sold under the brand name Forxiga) shows that the drug is effective at reducing HbA1c, body weight and systolic blood pressure but was associated with higher risks of health problems such as kidney problems and genital infections.
Forxiga is a type 2 diabetes drug within the SGLT-2 inhibitors class of diabetes medications. The drug acts to prevent the kidneys from reabsorbing a proportion of the glucose they remove from the blood back into the bloodstream. As a result, the drug helps to remove more glucose from the blood and release it from the body via the urine.
The study was carried out by researchers from AstraZenecan, the makers of Forxiga, as well as researchers from the Louisiana State University System and the University of Toronto. Whilst a number of studies into drug safety need to be carried out before a drug is approved, further safety studies, known as post-marketing studies, are also carried out following approval to confirm safety.
Post-marketing studies can be useful for catching health risks which may only develop after a number of years of taking the drug. In this study, the time period was 24 weeks, in which patients were unaware whether they were taking dapagliflozin or a placebo, followed by a 28 week extension period.
To assess effectiveness, the researchers compared, between dapagliflozin and placebo users, the percentage of patients that achieved the following three end points:
5.5 mmol/mol (0.5%) or greater reduction in HbA1c
Loss of 3% or more of body weight
Reduction in systolic blood pressure of 3 mmHg or more
The results of the study showed that, after the initial 24 weeks study period, 11.7% of patients taking dapagliflozin met each of the three end points compared to 0.9% of those on the placebo. These changes were maintained over the additional 28 weeks extension period. The average reduction in HbA1c of the patients taking dapagliflozin was 4.8 mmol/mol (0.38%).
Dapagliflozin use was not associated with increased rates of hypoglycemia (low blood sugar levels), urinary tract infections or cardiac problems compared with placebo. However greater rates of hypotension (low blood pressure levels)/dehydration/hypovolemia (loss of blood volume), renal failure or impairment and genital infections.
The lack of increased risk of heart problems is reassuring as a number of other tablets for treating type 2 diabetes, notably thiazolidinediones (such as Actos), have been linked with increased risks of heart problems. The increased rate of renal impairment (which results from some degree of damage within the kidney) stands out as a cautionary marker which should be taken into account by doctors and patients.
Patients taking dapagliflozin should have their kidney function monitored regularly as the drug’s action depends upon the kidneys being able to adequately filter the blood. This therefore provides a safety net, within the UK, towards minimising any possible risk to the kidneys. As a general rule, Diabetes.co.uk advises all diabetes patients to ensure you are informed by your health team as to whether any signs of complications are progressing.
Currently, other post-marketing studies, the DECLARE and MACE trials, are running and are due to be completed in June 2019. The role of these studies will be to review and assess the safety of the drug with regard to the risks of kidney, heart, liver and bone problems in addition to other possible health risks.