Comparing second-line therapy options combined with metformin for patients with type 2 diabetes.

This study explored the effects of different second-line therapies combined with metformin (Glucophage) in patients with type 2 diabetes (T2D). The data showed that metformin combinations with a sulfonylurea (SU) had the lowest weight loss, the smallest effect of lowering blood glucose, and an overall, reduced health status.

Metformin is usually administered as a first-line therapy for patients with T2D. Patients unable to attain optimal blood glucose control (HbA1c levels of 7% or less) may require second-line therapy.

Second-line therapy options include SUs, dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 (GLP-1) receptor agonists. However, there is no standard choice for optimal second-line therapy. What is the optimal combination for second-line therapy in patients with T2D uncontrolled with metformin is still unknwon.

This study included 7613 adult patients starting a second-line glucose-lowering therapy. 40.9% of patients received metformin and an SU, while 48.3% received metformin and a DPP-4i. 8.3% of patients were given metformin and an SGLT-2i, and 2.4% received metformin and a GLP-1 receptor agonist. Patients were evaluated for up to 36 months.

At 6 and 12 months, significantly greater reductions in HbA1c levels occurred with metformin combinations and either a DPP-4i or an SGLT-2i, or a GLP-1 receptor agonist, when compared to SU combinations. Similar reductions in HbA1c levels occurred with all combinations after 36 months.

Greater weight loss occurred with metformin and GLP-1 receptor agonist combinations (5 kg), metformin and SGLT-2i combinations (2.9 kg), and metformin and DPP-4i combinations (1.9 kg), compared to metformin and SU combinations (1.3 kg).

11.9% of patients taking metformin and SUs experienced one or more episodes of low blood glucose (hypoglycemia), compared to other combinations (3.9% to 6.4%).

Health survey scores (SF-36v2) that evaluate quality of life were lowest for patients that received metformin and SU combinations.

The study showed that metformin combined with a DPP-4i, an SGLT-2i or a GLP-1 receptor agonist produced more favorable results in patients with T2D compared to a SU combination.

The study did not assess kidney and cardiovascular-related complications. A small number of patients were given metformin with an SGLT-2i or a GLP-1 receptor agonist.