Second-Line Therapies Show Benefit Over Metformin Monotherapy in T2D

Investigators assessed the effect of second-line therapies on weight, HbA1c, and treatment persistence over 18 months in patients who had received metformin monotherapy.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitor, when used as a second-line therapy for type 2 diabetes, helped reduce glycated hemoglobin (HbA1c) by at least 0.5% and weight by at least 2 kg in over one-third of patients in 18 months, according to a study published in BMC Medicine.

The researchers of this retrospective study analyzed the benefits of adding a second-line glucose-lowering therapy to metformin on HbA1c levels, weight reduction, and treatment persistence in adults with type 2 diabetes. Patients were grouped into arms on the basis of their second-line therapy: sulfonylurea (n=4655), dipeptidyl peptidase-4 (DPP-4) inhibitor (n=2899), sodium–glucose cotransporter 2 (SGLT-2) inhibitor (n=441), or all other therapies (n=1102). HbA1c levels and body weight were recorded at baseline and at 6, 12, and 18 months.

In regard to patients remaining on their baseline therapy, the SGLT-2 inhibitor group had the highest consistency rate, at 57.7%, and the all other therapy groups had the lowest consistency rate, at 47.2%. As a whole, patients who did not change or adjust their therapy had a change in HbA1c of -1.38% at 6 months, -1.32% at 12 months, and -1.20% at 18 months. The sulfonylurea and SGLT-2 inhibitor groups had significant reductions of HbA1c at 6 months (-1.33% and -1.26%, respectively; P <.001), and the SGLT-2 inhibitor group had the greatest reductions at 18 months (-1.46%). Over the 18-month period, patients in the SGLT-2 inhibitor group and the DPP-4 inhibitor group had significant reductions in mean weight (-4.2 kg and -1.5 kg respectively; P <.001). Overall, the SGLT-2 inhibitor group had the greatest treatment success, with 36.5% of patients continuing on treatment, reducing HbA1c by at least 0.5%, and reducing weight by at least 2 kg. DPP-4 inhibitors had a success rate of 17.1%, sulfonylurea had a success rate of 9.6%, and all other therapies had a success rate of 9.1%.

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Some limitations of this study were the reduction of patients due to changing therapies from baseline to 18 months and the limited number of patients on DPP-4 and SGLT-2 inhibitors (because these are newer forms of treatment and not widely used at the time of data collection). Future studies need to expand on these results by analyzing other first-line treatments with these second-line therapies. 

In conclusion, all groups of this study had reductions in HbA1c levels, with patients adding SGLT-2 inhibitors having the greatest reduction. SGLT-2 inhibitors also had the highest treatment success rate, which could make this family of therapies a viable option for patients.

This study was supported by AstraZeneca. Please refer to reference for a complete list of authors’ disclosures.


Wilding J, Godec T, Khunti K, et al. Changes in HbA1c and weight, and treatment persistence, over the 18 months following initiation of second-line therapy in patients with type 2 diabetes: results from the United Kingdom Clinical Practice Research Datalink. BMC Med. 2018;16(1):116.