Background: International guidelines recommend metformin as first-line therapy in people with type 2 diabetes (T2D). Many patients will eventually need dual therapy; sulfonylureas (SUs) and dipeptidyl-peptidase 4 inhibitors (DPP-4i) remain the most commonly prescribed second-line therapies. Available evidence, mostly from RCTs, generally indicates greater HbA1c reductions with SUs. No real-world comparative effectiveness studies have compared gliclazide MR, a later generation SU, and sitagliptin, the most commonly used DPP-4i.

Aim: To investigate the effectiveness of gliclazide MR vs. sitagliptin as second-line therapies in people with T2D uncontrolled on metformin monotherapy.

Methods: New users of gliclazide MR or sitagliptin were identified (1:1 high-dimensional propensity score matching) in the UK Clinical Practice Research Datalink (CPRD) database between 1/1/2010 and 21/10/2019, from a cohort of adults with T2D. A Cox model was used to estimate time to HbA1c <7.0% (primary outcome); secondary outcomes included time to HbA1c ≤6.5%.

Results: A total of 2346 patients (59.3% men; mean age 63 years, HbA1c 8.5%, diabetes duration 4.3 years) were included. Patients were 28% more likely to reach HbA1c <7% (HR [95% CI]: 1.28 [1.10-1.49]) and 50% more likely to reach HbA1c ≤6.5% (1.50 [1.19-1.93]) with gliclazide MR vs. sitagliptin. The difference in favour of gliclazide MR was maintained across patients’ characteristics (ethnicity, cardiorenal disease, age, diabetes duration, baseline HbA1c). Durability (time until switch or an add-on of a new drug or a stop) and persistence (duration of index drug) were similar. There was no significant difference in severe and nonsevere hypoglycaemic events.

Conclusion: These results demonstrate greater real-world effectiveness of gliclazide MR vs. sitagliptin as second-line therapy after metformin, with a similar persistence, durability and rate of hypoglycaemia.

Disclosure

F. Zaccardi: Speaker’s Bureau; Self; Napp Pharmaceuticals. V. Cortese: Employee; Self; Servier. E. Jacquot: Employee; Self; Servier. F. Tyrer: None. S. Seidu: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Servier. Board Member; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Sanofi-Aventis. Speaker’s Bureau; Self; Amgen, Lilly Diabetes, Merck Sharp & Dohme Corp. M.J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi, Sanofi US. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Other Relationship; Self; Ingeus UK. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.