Effects Of Second-Line Metformin Combination Therapies On Weight, Hba1c, And Risk Of Hypoglycemia Over 3 Years: The Discover Study

Background: We used DISCOVER, a 3-year observational study of people with T2D, to assess the effects of second-line metformin combination therapies on weight, HbA1c level and risk of hypoglycemia. Methods: Adjusted changes from baseline in weight and HbA1c level at 6, 12, 24 and 36 months were assessed using linear mixed models. An interval censored analysis was used to assess the risk of hypoglycemia. Results: At baseline, 7613 patients from 37 countries received second-line therapy with metformin and a dipeptidyl peptidase-4 inhibitor (DPP-4i; 48.3%), a glucagon-like peptide-1 receptor agonist (GLP-1 RA; 2.4%), a sodium-glucose co-transporter 2 inhibitor (SGLT2i; 8.3%) or a sulfonylurea (SU; 40.9%). When used in combination with metformin, GLP-1 RAs, SGLT2is and DPP-4is were associated with greater weight loss than SUs at all time points (Figure). Beyond 12 months, changes in HbA1c from baseline were similar for all combinations. Patients prescribed metformin and an SU had a greater occurrence of hypoglycemia over 3 years (11.9%) compared with the other combinations (3.9-6.4%). Conclusions: A high proportion of patients received metformin and a DPP-4i or an SU as a second-line therapy. All combinations showed a similar reduction in HbA1c. However, combinations of metformin and an SU were associated with the highest risk of hypoglycemia and the lowest weight reduction. Disclosure 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. B. Charbonnel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; AstraZeneca. A. Cooper: Employee; Self; AstraZeneca. M.B. Gomes: None. L. Ji: None. P. Leigh: Employee; Self; AstraZeneca. Employee; Spouse/Partner; Merck Sharp & Dohme Corp. A. Nicolucci: Consultant; Self; AstraZeneca. W. Rathmann: Advisory Panel; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Research Support; Self; Novo Nordisk Inc. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. M.V. Shestakova: None. A. Siddiqui: None. F. Tang: Research Support; Self; AstraZeneca. H. Watada: Advisory Panel; Self; Abbott, Ajinomoto, Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Fuji Film, Janssen Pharmaceuticals, Inc., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Yakult. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. H. Chen: None. Funding AstraZeneca