677-P: Remission of Type 2 Diabetes following Intensive Treatment with Insulin Glargine, Lixisenatide, Metformin, and Lifestyle Approaches: Results of a Multicenter Randomized Controlled Trial
Authors: MCINNES NATALIA , HALL STEPHANIE , LOCHNAN HEATHER A. , HARRIS STEWART B. , PUNTHAKEE ZUBIN , SIGAL RONALD J. , HRAMIAK IRENE , AZHARUDDIN MOHAMMED , LIUTKUS JOANNE F. , YALE JEAN-FRANÇOIS , SULTAN FARAH , SMITH ADA C. , OTTO ROSE E. , SHERIFALI DIANA , LIU YAN YUN , GERSTEIN HERTZEL C. ,   REMIT-IGLARLIXI COLLABORATIVE GROUP
Published: June 2021

Background: Diabetes remission due to non-surgical approaches has not been well studied. We investigated induction of diabetes remission following a short-term treatment with insulin glargine, lixisenatide and metformin and changes in exercise and dietary behaviours.
Methods: We randomized 160 individuals with type 2 diabetes to (i) 12-week intensive treatment with insulin glargine, lixisenatide, metformin and lifestyle approaches or (ii) standard glycemic management. At 12 weeks, diabetes medications were stopped in patients with HbA1C&lt;7.3%, and participants were followed for diabetes relapse over the subsequent 52 weeks. Diabetes relapse was defined as either the use of diabetes medications, ≥50% of capillary glucose levels ≥10 mmol/L over 1 week, or HbA1C≥6.5% at 24, 36, 48 or 64 weeks and analyzed as time to event. Treatment groups were compared using a Cox Proportional Hazards model with adjustment for duration of diabetes and baseline HbA1C (primary analysis). Key secondary outcomes included the proportion of participants in remission at 24, 36, 48 and 64 weeks.
Results: The intervention significantly reduced the hazard of diabetes relapse (HR 0.57, 95% CI 0.40-0.81; p=0.002). The proportion of participants with diabetes remission was significantly higher in the intervention group compared to the control group at 24 weeks (38% vs. 20%; relative risk RR 1.92 (1.14-3.24)) and at 36 weeks (32% vs. 17%; RR 1.83 (1.03-3.26)), but not at 48 and 64 weeks (RR 1.88 (1.00-3.53) and 2.05 (0.98-4.29), respectively).
Conclusion: Short-term intensive treatment targeting normoglycemia and weight loss with insulin glargine, lixisenatide, metformin and lifestyle changes can induce sustained remission of type 2 diabetes.

Disclosure
N. Mcinnes: Other Relationship; Self; Merck & Co., Inc., Novo Nordisk, Sanofi. J. Yale: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Self; Bayer Inc., Speaker’s Bureau; Self; Dexcom, Inc., Medtronic, Merck & Co., Inc., Omnipod. F. Sultan: Employee; Self; Abbott Diabetes. A. C. Smith: None. R. E. Otto: None. D. Sherifali: None. Y. Liu: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Remit-iglarlixi collaborative group: n/a. S. Hall: None. H. A. Lochnan: Research Support; Self; Novo Nordisk Inc., Sanofi. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Z. Punthakee: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Self; AstraZeneca, Lexicon Pharmaceuticals, Inc., Novo Nordisk. R. J. Sigal: Advisory Panel; Self; Novo Nordisk, Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk. I. Hramiak: Advisory Panel; Self; AstraZeneca, Bayer Inc., BI-Lilly Joint Venture (Boehringer Ingelheim and Eli Lilly), Dexcom, Inc., Insulet Corporation, Medtronic, Research Support; Self; Eli Lilly and Company, Novo Nordisk, Sanofi. M. Azharuddin: Consultant; Self; Novo Nordisk Canada Inc. J. F. Liutkus: Advisory Panel; Self; Novo Nordisk Canada Inc., Research Support; Self; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., IQVIA, Kowa Research Institute, Inc., Novo Nordisk Canada Inc., Sanofi, Speaker’s Bureau; Self; Novo Nordisk Canada Inc., Stock/Shareholder; Self; Bayer Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Spouse/Partner; Bayer Inc., Eisai Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Pfizer Inc.

Funding
Sanofi