PP05-4 Liraglutide 3.0 Mg Reduces the Prevalence of Prediabetes and Delays Onset of Type 2 Diabetes in Overweight and Obese Adults: Results from Scale Obesity and Prediabetes, a Randomized, Double-Blind and Placebo-Controlled 56-Week Trial

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: PP05-Peripheral Regulation of Energy Homeostasis
Basic/Clinical
Saturday, June 21, 2014: 11:15 AM-11:30 AM
W178 (McCormick Place West Building)

Poster Board SAT-0925
F Xavier Pi-Sunyer, MD, MPH1, Arne Astrup, MD2, Ken Fujioka, MD3, Frank Lyons Greenway III, MD4, Alfredo Halpern, MD5, Michel Krempf, MD, PhD6, David C Lau, MD PhD7, Carel Le Roux, MD, PhD8, Rafael Violante Ortiz, MD9, Christine Bjørn Jensen, MD, PhD10 and John Wilding, DM, FRCP11
1St Luke's Roosevelt Hosp, New York, NY, 2University of Copenhagen, Frederiksberg C, Denmark, 3Scripps Clinic, La Jolla, CA, 4Pennington Biomed Res Ctr, Baton Rouge, LA, 5Universidade Sao Paulo, Sao Paulo, Brazil, 6Hopital Nord - Laennec, Nantes, France, 7University of Calgary, Calgary, AB, Canada, 8University College Dublin, Dublin, Ireland, 9Instituto Mexicano del Seguro Social, Cuidad Madero, Tamaulipas, Mexico, 10Novo Nordisk A/S, Søborg, Denmark, 11University of Liverpool, Liverpool, United Kingdom
Obesity is associated with prediabetes, a significant risk factor for development of type 2 diabetes mellitus (T2DM) and its accompanying complications. This trial investigated the effects of liraglutide 3.0 mg, as adjunct to diet and exercise, on weight loss (primary endpoint), prediabetes prevalence and onset of T2DM (ADA 2010 criteria) over 56 weeks. The effects of liraglutide 3.0 mg cessation were investigated in a subsequent 12‑week re-randomized period.

Adults (BMI ≥27 kg/m2 with ≥1 comorbidity or ≥30 kg/m2) were advised on a 500 kcal/day deficit diet and exercise program and randomized 2:1 to once-daily s.c. liraglutide 3.0 mg or placebo. Randomization was stratified by prediabetes status (ADA 2010 criteria). At week 56, individuals without prediabetes and on liraglutide 3.0 mg were re-randomized 1:1 to liraglutide 3.0 mg or placebo (diet and exercise continued). The trial has an ongoing 2-year extension for individuals with prediabetes. Clinicaltrials.gov ID: NCT01272219.

Of 3731 randomized individuals (age 45.1 years, 78.5% female, body weight 106.2 kg, BMI 38.3 kg/m2, 61.2% with prediabetes), 71.9% on liraglutide 3.0 mg and 64.4% on placebo completed 56 weeks.

At week 56, individuals on liraglutide 3.0 mg (n=2432) had lost 8.0% (8.4 kg) of body weight compared to 2.6% (2.8 kg) on placebo (n=1220) (estimated treatment difference [ETD] 5.4% [5.6 kg], p<0.0001, LSmeans, full analysis set with LOCF, ANCOVA).

Liraglutide 3.0 mg improved fasting and post-load glycemia compared to placebo (ETD FPG ‑6.9 mg/dL, PG [OGTT, area under the curve] ‑36.4 h*mg/dL, HbA1c ‑0.23 %-points; p<0.0001 for all). Accordingly, of those with prediabetes at screening, more individuals had reverted to normoglycemia on liraglutide 3.0 mg (69.7%) than on placebo (32.1%) at week 56 (estimated odds ratio [OR] 4.85, p<0.0001, LSmeans, logistic regression). Likewise, of those with normoglycemia at screening, more individuals had progressed to prediabetes on placebo (19.9%) than on liraglutide 3.0 mg (6.9%) at week 56 (OR 3.3, p<0.0001). Few individuals developed T2DM during treatment, but more did so on placebo (14 individuals, 1.3 events/100 patient years of exposure [PYE]) than on liraglutide 3.0 mg (4 individuals, 0.2 events/100 PYE) (OR 0.12, p=0.0003).

From week 56 to 68, individuals re-randomized from liraglutide 3.0 mg to placebo regained more weight (2.9%) than individuals staying on liraglutide 3.0 mg (0.7%) (ETD 2.2%, p<0.0001), and more individuals progressed to prediabetes on placebo (from 8.0% to 22.4%, observed means) than on liraglutide 3.0 mg (from 9.1% to 8.6%) (p<0.0001). No individuals developed T2DM.

In conclusion, consistent with the combined effects on body weight and glycemia, liraglutide 3.0 mg, as adjunct to diet and exercise, was superior to placebo in reducing the prevalence of prediabetes and T2DM after 56 weeks of treatment. Continued treatment was required to sustain these effects.

Disclosure: FXP: Medical Advisory Board Member, Novo Nordisk, Medical Advisory Board Member, Weight Watchers, Medical Advisory Board Member, Johnson &Johnson, Medical Advisory Board Member, Vivus USA, Medical Advisory Board Member, Zafgen, Medical Advisory Board Member, Eisai. AA: Advisory Group Member, BioCare, Advisory Group Member, Pathway Genomics Corp, Advisory Group Member, Vivus USA, Board Member, Dentacom Aps, Shareholder, Dentacom Aps, Consultant, Arena Pharmaceuticals Inc, Consultant, Basic Research , Consultant, Boehringer Ingelheim Pharma GmbH & Co KG, Consultant, Gelesis, Consultant, Gerson Lehrman Group, Consultant, Novo Nordisk, Consultant, S-Biotek, Consultant, Twinlab. KF: Consultant, Eisai, Speaker Bureau Member, Eisai, Consultant, NPS, Speaker Bureau Member, NPS, Consultant, Vivus USA, Speaker Bureau Member, Vivus USA, Consultant, Isis, Consultant, NaZura, Consultant, Novo Nordisk, Consultant, Zafgen, Consultant, Orexigen, Speaker Bureau Member, Abbott Laboratories, Speaker Bureau Member, Takeda, Researcher, Eisai, Researcher, Novo Nordisk, Researcher, NPS, Researcher, Orexigen, Researcher, Enteromedics, Researcher, Shire, Speaker Bureau Member, WeightWatchers. FLG III: Patent holder, Patent holdings, Consultant, Align2Action, Consultant, BARONova, Consultant, Basic Research, Consultant, Citius Pharmaceutical, Editorial Board member, Diabetic Living, Consultant, Eisai, Consultant, General Nutrition Corp, Consultant, Medacorp, Consultant, Guidepoint Global, Consultant, Japan Tobacco Pharmaceutical Division, Medical Advisory Board Member, Jenny Craig, Consultant, Lithera Inc, Patents licencee and stockholder, NeuroQuest, Scientific Board Member, Novo Nordisk, Stockholder, NuMe Health, Scientific Board Member, Orexigen, Stockholder, Origin Biomed, Advisory Group Member, Pam Labs, Stockholder, PlenSat, Consultant, Thetis Pharmaceuticals, Consultant, Unigene Labs, Advisory Group Member, Zafgen, Researcher, Novo Nordisk, Researcher, Hanmi Pharmaceuticals. AH: Advisory Group Member, Novo Nordisk, Speaker Bureau Member, Novo Nordisk. MK: Medical Advisory Board Member, Astra Zeneca, Medical Advisory Board Member, Bristol-Myers Squibb, Medical Advisory Board Member, Novo Nordisk. DCL: Researcher, Astra Zeneca, Researcher, Boehringer Ingelheim, Researcher, Bristol-Myers Squibb, Researcher, Eli Lilly & Company, Researcher, Novo Nordisk, Medical Advisory Board Member, Amgen, Medical Advisory Board Member, Astra Zeneca, Medical Advisory Board Member, Boehringer Ingelheim, Medical Advisory Board Member, Bristol-Myers Squibb, Medical Advisory Board Member, Jansen Pharmaceuticals, Medical Advisory Board Member, Eli Lilly & Company, Medical Advisory Board Member, Novo Nordisk, Medical Advisory Board Member, Roche Pharmaceuticals, Medical Advisory Board Member, Valeant Pharmaceuticals, Speaker Bureau Member, Amgen, Speaker Bureau Member, Astra Zeneca, Speaker Bureau Member, Boehringer Ingelheim, Speaker Bureau Member, Bristol-Myers Squibb, Speaker Bureau Member, Eli Lilly & Company, Speaker Bureau Member, Merck & Co., Speaker Bureau Member, Novo Nordisk, Speaker Bureau Member, Valeant Pharmaceuticals. CL: Medical Advisory Board Member, Novo Nordisk. RV: Medical Advisory Board Member, Merck Sharp & Dohme, Medical Advisory Board Member, Boehringer Ingelheim, Medical Advisory Board Member, Novo Nordisk, Medical Advisory Board Member, Bristol-Myers Squibb, Medical Advisory Board Member, Astra Zeneca, Medical Advisory Board Member, Eli Lilly & Company, Researcher, Eli Lilly & Company, Researcher, Novo Nordisk, Speaker Bureau Member, Merck Sharp & Dohme, Speaker Bureau Member, Boehringer Ingelheim, Speaker Bureau Member, Novo Nordisk, Speaker Bureau Member, Bristol-Myers Squibb, Speaker Bureau Member, Astra Zeneca. CBJ: Employee, Novo Nordisk, Employee, Novo Nordisk. JW: Speaker Bureau Member, Novo Nordisk, Medical Advisory Board Member, Novo Nordisk, Speaker Bureau Member, Eli Lilly & Company, Speaker Bureau Member, Jansen Pharmaceuticals, Medical Advisory Board Member, Jansen Pharmaceuticals, Speaker Bureau Member, Bristol-Myers Squibb, Researcher, Bristol-Myers Squibb, Medical Advisory Board Member, Bristol-Myers Squibb, Speaker Bureau Member, Boehringer Ingelheim, Speaker Bureau Member, Astra Zeneca, Medical Advisory Board Member, Astra Zeneca, Medical Advisory Board Member, Astellas, Researcher, Novo Nordisk, Speaker Bureau Member, Merck & Co..

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

Sources of Research Support: Supported by Novo Nordisk
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