Temporal Trends in the Use of Sodium-Glucose Cotransporter 2 Inhibitors—The Global DISCOVER Study
Authors: KOSIBOROD MIKHAIL , CHEN HUNGTA , CID-RUZAFA JAVIER , FENICI PETER , GOMES MARILIA B. , HAMMAR NIKLAS , KHUNTI KAMLESH , POCOCK STUART , SHESTAKOVA MARINA V. , SHIMOMURA IICHIRO , SURMONT FILIP , TANG FENGMING , JI LINONG 
Published: June 2018

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of cardiovascular (CV) events in patients with type 2 diabetes (T2D), first demonstrated in the EMPA-REG OUTCOME trial (EMPA-REG). We examined trends in the use of SGLT2i during the first year of DISCOVER (NCT02322762), a 3-year observational study of patients with T2D initiating second-line glucose-lowering therapy in 37 countries.
Methods: Patients who weren’t receiving an SGLT2i at first-line and who had data on glucose-lowering medications at baseline, 6 and 12 months were included (N = 11 706). We assessed the numbers and characteristics of patients who were initiated on an SGLT2i (initiation of second-line therapy at baseline, or later-line therapy during the first year of follow-up) overall and according to whether the date of initiation was before or after EMPA-REG.
Results: Overall, 1138 patients were prescribed an SGLT2i at baseline or during follow-up (9.7%; across-country range: 0.0-68.9%). There were no substantial differences in patient characteristics among those who were prescribed an SGLT2i before or after EMPA-REG: 10.4% (before) and 14.4% (after) of patients had a history of macrovascular complications, compared with 12.9% of patients prescribed a different class of medication (p = 0.24). At baseline (initiation of second-line therapy), the proportion of patients who received an SGLT2i was higher when the initiation occurred after vs. before EMPA-REG (8.4% vs. 5.9%, p &lt; 0.001).
Conclusions: The overall proportion of patients prescribed an SGLT2i was low, but varied greatly across countries. SGLT2i use increased modestly after EMPA-REG. Although the CV benefits of SGLT2i use have been best demonstrated in people with established macrovascular disease, the clinical decision to prescribe these agents does not appear to be primarily driven by the presence of macrovascular complications.

Disclosure
M. Kosiborod: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Amgen Inc., Sanofi, Boehringer Ingelheim GmbH, GlaxoSmithKline plc., Glytec Systems, Merck & Co., Inc., Novo Nordisk A/S, Janssen Pharmaceuticals, Inc., ZS Pharma, Inc., Intarcia Therapeutics, Inc., Novartis AG. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. H. Chen: Employee; Self; AstraZeneca. J. Cid-Ruzafa: Employee; Self; Evidera. P. Fenici: Employee; Self; AstraZeneca. M.B. Gomes: Advisory Panel; Self; AstraZeneca. Consultant; Self; Merck KGaA. N. Hammar: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. K. Khunti: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Sanofi-Aventis, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Sanofi-Aventis, Pfizer Inc.. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; Novo Nordisk A/S. Consultant; Self; Pfizer Inc.. Research Support; Self; Novo Nordisk A/S. S. Pocock: Consultant; Self; AstraZeneca. M.V. Shestakova: None. I. Shimomura: Research Support; Self; Appliance Company, Panasonic Corporation. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Covidien Japan Inc.. Research Support; Self; Daiichi Sankyo Company, Limited. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Eli Lilly Japan K.K., Eli Lilly Japan K.K., Kaken Pharmaceutical Co., Ltd.. Speaker's Bureau; Self; Kowa Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K.. Research Support; Self; Novo Nordisk Pharma Ltd.. Speaker's Bureau; Self; Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd.. Research Support; Self; Roche DC Japan K.K., Rohto Pharmaceutical Co., Ltd. Speaker's Bureau; Self; Rohto Pharmaceutical Co., Ltd, Sanwa Kagaku Kenkyusho Co., Ltd.. Research Support; Self; Sanofi K.K.. Speaker's Bureau; Self; Sanofi K.K.. Research Support; Self; Shionogi & Co., Ltd.. Speaker's Bureau; Self; Sumitomo Dainippon Pharma Co., Ltd.. Research Support; Self; Taisho Toyama Pharmaceutical Co., Ltd.. Speaker's Bureau; Self; Taisho Toyama Pharmaceutical Co., Ltd.. Research Support; Self; Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. Research Support; Self; Teijin Pharma Limited. Speaker's Bureau; Self; Teijin Pharma Limited. F. Surmont: Employee; Self; AstraZeneca. F. Tang: Research Support; Self; AstraZeneca. Employee; Self; Mid America Heart Institute. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Eli Lilly and Company, Bristol-Myers Squibb Company, Novartis AG, Novo Nordisk A/S, Merck & Co., Inc., Bayer AG, Merck Sharp & Dohme Corp., Takeda Development Center Asia, Pte. Ltd., Sanofi, Roche Pharma, Boehringer Ingelheim GmbH. Research Support; Self; AstraZeneca, Roche Pharma, Sanofi, Merck Sharp & Dohme Corp., Novartis AG, Eli Lilly and Company, Bristol-Myers Squibb Company.