Changes in HbA1c and weight, and treatment persistence, over the 18\xa0months following initiation of second-line therapy in patients with type 2 diabetes: results from the United Kingdom Clinical Practice Research Datalink

John Wilding,Jesús Medina,Robin Fox,Kamlesh Khunti,Liam Smeeth,Peter Fenici,Per Clauson,Niklas Hammar,Thomas Godec,Stuart Pocock

doi:10.1186/s12916-018-1085-8

Abstract

BackgroundIntensification of metformin monotherapy with additional glucose-lowering drugs is often required in patients with type 2 diabetes (T2D). This study evaluated changes in HbA1c and weight, as well as treatment persistence, associated with different second-line therapies used in UK clinical practice.MethodsThe UK Clinical Practice Research Datalink was used to identify patients with T2D who initiated second-line therapy after metformin monotherapy between 1 August 2013 and 14 June 2016. Treatment persistence and changes in HbA1c and weight were assessed at 6-month intervals up to 18 months.ResultsIn total, 9097 patients (mean age 61.2 years, 57.2% men, mean [standard deviation] HbA1c 9.0% [1.8]/ 75 mmol/mol [19.7]) were included in the analysis, with a median 2.3 years between initiating metformin monotherapy and initiating second-line therapy. Patients were stratified according to second-line therapy: metformin in combination with sulfonylurea (SU; n = 4655 [51.2%]), a dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor; n = 2899 [31.9%]), or a sodium–glucose cotransporter-2 inhibitor (SGLT-2 inhibitor; n = 441 [4.9%]) or other therapies (all other second-line treatments; n = 1102 [12.1%]). At 18 months, the cumulative proportion of patients changing treatment was lowest for those who received metformin plus an SGLT-2 inhibitor (42.3%), followed by patients on metformin plus SU or metformin plus a DPP-4 inhibitor (46.8%). HbA1c reductions were seen with all second-line therapies, with an overall mean (standard error) reduction of −1.23% (0.05)/−13.4 mmol/mol (0.5). Changes were directly, but not linearly, related to baseline HbA1c and were greater in those with higher HbA1c at baseline. Weight loss from baseline was greatest in patients treated with metformin plus either an SGLT-2 inhibitor (−4.2 kg) or a DPP-4 inhibitor (−1.5 kg). The highest proportion of patients who achieved the composite outcome of HbA1c reduction ≥ 0.5%, body weight loss ≥ 2.0 kg and treatment persistence for 18 months was observed in those receiving metformin plus an SGLT-2 inhibitor (36.5%).ConclusionsIn this population-based cohort, all second-line therapies added to metformin monotherapy improved glycaemic control, but the lowest treatment change/discontinuation rate and most sustained weight loss was seen with patients receiving metformin plus an SGLT-2 inhibitor.

Highlights

Intensification of metformin monotherapy with additional glucose-lowering drugs is often required in patients with type 2 diabetes (T2D)
Wilding et al BMC Medicine (2018) 16:116 (Continued from previous page). In this population-based cohort, all second-line therapies added to metformin monotherapy improved glycaemic control, but the lowest treatment change/discontinuation rate and most sustained weight loss was seen with patients receiving metformin plus an sodium–glucose cotransporter-2 (SGLT-2) inhibitor
Patient populations From the initial 407,700 patients screened, we identified 9097 patients with Type 2 diabetes (T2D) who had received first-line metformin monotherapy and were initiated on second-line treatment (Additional file 1: Figure S1)

Summary

Introduction

Intensification of metformin monotherapy with additional glucose-lowering drugs is often required in patients with type 2 diabetes (T2D). Current guidelines recommend the use of metformin as the preferred first-line glucose-lowering therapy in patients with T2D [4]. In view of its progressive nature, the majority of patients with T2D require treatment intensification from metformin monotherapy to achieve and maintain recommended HbA1c targets [6]. The National Institute for Health and Care Excellence (NICE) guidelines and the position statement of the American Diabetes Association and the European Association for the Study of Diabetes recommend that initial treatment intensification after failure of metformin monotherapy should consist of dual therapy with one of the following agents: DPP-4 inhibitors, pioglitazone, SUs or SGLT-2 inhibitors [4, 6]. The choice of second-line agent should be based upon patient-specific considerations to minimise side effects whilst reducing HbA1c levels [7]

Methods

Results

Discussion

Conclusion