Metformin can be used more widely, study suggests

Alexandra Kirsten
The effectiveness and overall benefits of the antidiabetic drug metformin far outweighs its risks, even in patients with renal
impairment, according to a Swedish study.

The long-term effectiveness and safety of glucose-lowering medications are under debate, said lead study author Dr.
Nils Ekstrm from the Sahlgrenska University Hospital in Sweden.

Metformin in particular is normally not prescribed for patients with reduced kidney function because the risk of adverse
effects is widely regarded as unacceptably high.

Ekstrm and his colleagues evaluated the risks of cardiovascular disease, lactic acidosis, serious infections and mortality
in 51,675 patients with type 2 diabetes registered in the Swedish National Diabetes Register (NDR).

The patients were grouped according to their medication (ie, metformin monotherapy, insulin monotherapy and therapy
with other oral hypoglycemic agents). The researchers analysed risks of fatal/non-fatal cardiovascular disease (CVD),
acidosis/serious infection and all-cause mortality in all patients and in subgroups with different estimated glomerular
filtration rate (eGFR) intervals. The mean follow-up of the study was 3.9 years equivalent to more than 200,000 patient-
years at risk.

After adjusting for clinical characteristics, risk factors and treatments, insulin monotherapy was associated with an
increased risk of fatal and non-fatal CVD and all-cause mortality compared with metformin monotherapy (95 % CI 1.07-
1.29 and 95% CI 1.19-1.50, respectively). In subgroup analyses, metformin was not associated with an increased risk of
any of the outcomes in patients with eGFR 30-45, 45-60, or >60 mL/min/1.73 m2 compared with all other hypoglycemic
agents.

Of note, on a subgroup of patients with renal impairment (eGFR 45-60 mL/min/1.73 m2), metformin showed a reduced
risk of any acidosis/serious infection and all-cause mortality.

In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects. These results support
the less strict approach to metformin use in patients with renal impairment advocated in most guidelines, the researchers
said. Thus, the drug can be prescribed for many more patients with diabetes than is currently the case.

According to Ekstrm, a number of other countries already recommend metformin for patients with mild kidney
impairment. Nevertheless, it is important to keep in mind that the results are for patients with mild to moderate kidney
impairment, he pointed out. Metformin still cannot be recommended for patients with severe kidney impairment and
should be prescribed with great caution for those patients.