medwireNews: Combining metformin with a sulfonylurea (SU) produces poorer non-glycemic outcomes than combining it with other second-line agents, show results from the global DISCOVER program.
All combinations resulted in similar glycemic control in the long term, but Kamlesh Khunti (University of Leicester, UK) and co-investigators stress that “it is important to consider other factors in the management of [type 2 diabetes].”
They found that use of metformin plus an SU resulted in less weight loss, more hypoglycemia, and poorer quality of life, compared with all other combinations.
“Despite this, combinations of metformin and an SU were prescribed to a large proportion of participants, echoing results from an observational study carried out in the UK and Germany,” the researchers write in Diabetes Obesity and Metabolism.
They attribute this to the low availability and high cost of alternative glucose-lowering medications in the lower-income countries included in the DISCOVER study program.
“For example, combinations of metformin and an SU were prescribed to 94% of patients from the African region, whereas in Europe such combinations were only prescribed to 30% of patients,” they say.
The DISCOVER program covers 38 countries, grouped into World Health Organization regions. This analysis included 7613 people, aged an average of 57 years, who were taking a metformin combination for type 2 diabetes. Of these people, 40.9% were using an SU, 48.3% a dipeptidyl peptidase (DPP)-4 inhibitor, 8.3% a sodium-glucose cotransporter (SGLT)2 inhibitor, and 2.4% a glucagon-like peptide (GLP)-1 receptor agonist.
Although people initially achieved significantly larger reductions in glycated hemoglobin with metformin combinations other than SUs, this difference disappeared after 12 months, at which point only use of a DPP-4 inhibitor was associated with significantly better glycemic control relative to use of an SU.
But people taking an SU with metformin had the smallest weight loss at all measured timepoints up to and including 36 months, whereas metformin plus a GLP-1 receptor agonist consistently delivered the largest reductions, of approximately 5 kg at 36 months, compared with 1 kg for the SU combination.
Hypoglycemic events were most common in people taking an SU with metformin, at around 12% by 36 months of treatment, compared with about 3–6% for the other metformin combinations.
Finally, people taking an SU with metformin had negative changes in mental quality of life at all timepoints, and in physical quality of life at most, although the researchers note that these changes from baseline were “modest.” By contrast, people taking other second-line agents had improvements at all or most timepoints.
“These real world data suggest that metformin in combination with a DPP-4 inhibitor, an SGLT-2 inhibitor, or a GLP-1 receptor agonist hold significant benefits at second line in comparison with metformin and an SU, adding additional evidence to support guidance which recommends SU combination therapies only if cost or availability is an issue,” conclude the researchers.
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Diabetes Obes Metab 2021; doi:10.1111/dom.14400